Science.gov

Sample records for rimboschimenti di douglasia

  1. Reticulate evolution in North American black-fruited hawthorns (Crataegus section Douglasia; Rosaceae): evidence from nuclear ITS2 and plastid sequences

    PubMed Central

    Zarrei, M.; Stefanović, S.; Dickinson, T. A.

    2014-01-01

    Background and Aims The taxonomic complexity of Crataegus (hawthorn; Rosaceae, Maleae), especially in North America, has been attributed by some to hybridization in combination with gametophytic apomixis and polyploidization, whereas others have considered the roles of hybridization and apomixis to be minimal. Study of the chemical composition and therapeutic value of hawthorn extracts requires reproducible differentiation of entities that may be difficult to distinguish by morphology alone. This study sought to address this by using the nuclear ribosomal spacer region ITS2 as a supplementary DNA barcode; however, a lack of success prompted an investigation to discover why this locus gave unsatisfactory results. Methods ITS2 was extensively cloned so as to document inter- and intraindividual variation in this locus, using hawthorns of western North America where the genus Crataegus is represented by only two widely divergent groups, the red-fruited section Coccineae and the black-fruited section Douglasia. Additional sequence data from selected loci on the plastid genome were obtained to enhance further the interpretation of the ITS2 results. Key Results In the ITS2 gene tree, ribotypes from western North American hawthorns are found in two clades. Ribotypes from diploid members of section Douglasia occur in one clade (with representatives of the east-Asian section Sanguineae). The other clade comprises those from diploid and polyploid members of section Coccineae. Both clades contribute ribotypes to polyploid Douglasia. Data from four plastid-derived intergenic spacers demonstrate the maternal parentage of these allopolyploids. Conclusions Repeated hybridization between species of section Douglasia and western North American members of section Coccineae involving the fertilization of unreduced female gametes explains the observed distribution of ribotypes and accounts for the phenetic intermediacy of many members of section Douglasia. PMID:24984714

  2. Thermodynamic black di-rings

    SciTech Connect

    Iguchi, Hideo; Mishima, Takashi

    2010-10-15

    Previously the five dimensional S{sup 1}-rotating black rings have been superposed in a concentric way by some solitonic methods, and regular systems of two S{sup 1}-rotating black rings were constructed by the authors and then Evslin and Krishnan (we called these solutions 'black di-rings'). In this place we show some characteristics of the solutions of five dimensional black di-rings, especially in thermodynamic equilibrium. After the summary of the di-ring expressions and their physical quantities, first we comment on the equivalence of the two different solution sets of the black di-rings. Then the existence of thermodynamic black di-rings is shown, in which both isothermality and isorotation between the inner black ring and the outer black ring are realized. We also give detailed analysis of peculiar properties of the thermodynamic black di-ring including discussion about a certain kind of thermodynamic stability (instability) of the system.

  3. Di(hydroxyphenyl)- benzimidazole monomers

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

    1993-01-01

    Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

  4. Trasforiiazioni Termoelastiche Finite di Solidi Incomprimibili

    NASA Astrophysics Data System (ADS)

    Signorini, A.

    Queste lezlioni hanno come direttiva una sintesi di quanto si trova sistematicamente sviluppato in una mia Memoria sulle trasformazioni termoelastiche finite di solidi incomprimibili, in corso di stampa negli Annali di Matematica pura e applicata t. XXXIX ( 1955) pp. 147-201 , Verranno anche esposti, come necessaria premessa, alcuni d ei risultati di due precedenti Memorie degli stessi Annali. Invece, per motivo di brevità, non potrò dare neppure un cenno delle ulteriori ricerche svilup pate dal prof. T. Manacorda in tre recentissimi suoi lavori:

  5. Di(2-ethylhexyl)adipate

    Integrated Risk Information System (IRIS)

    Di ( 2 - ethylhexyl ) adipate ; CASRN 103 - 23 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Non

  6. The "Bestie di Satana" murders.

    PubMed

    Birkhoff, Jutta; Candelli, Chiara; Zeroli, Stefania; La Tegola, Donatella; Carabellese, Felice

    2013-11-01

    In recent years, satanic groups have been responsible for various types and degrees of crimes. We report the case of a number of murders committed in Italy by a group of young people calling themselves the "Bestie di Satana". Forensic psychiatric assessment of the members of a satanic sect charged with the crime revealed that all the young people had a fragile, immature personality, a very low level of education and were socially disadvantaged. The trial of the members of the "Bestie di Satana" sect was concluded with the verdict of deliberate murder, and all the members were given long jail sentences. This report should lead us to explore social and cultural responses to juvenile satanism, statistically shown to be a relatively rare phenomenon but with a high criminal potential.

  7. Introduzione al Laboratorio di Fisica

    NASA Astrophysics Data System (ADS)

    Ciullo, Giuseppe

    La Fisica (dal greco τὰ ϕυσικὰ: le cose naturali) si pone l'obiettivo di descrivere e prevedere il comportamento dei fenomeni naturali, nonché degli apparati e degli strumenti, che hanno reso e rendono la nostra vita più comoda ed efficiente. Tale obiettivo viene perseguito mediante un'attenta osservazione dei fenomeni, con una conseguente schematizzazione dell'osservazione, per fornire una conoscenza della realtà oggettiva, affidabile, verificabile e condivisibile.

  8. Exclusive e+e-, di-photon and di-jet production at the Tevatron

    SciTech Connect

    Terashi, Koji; /Rockefeller U.

    2007-05-01

    Results from studies on exclusive production of electron-position pair, di-photon, and dijet production at CDF in proton-antiproton collisions at the Fermilab Tevatron are presented. THe first observation and cross section measurements of exclusive e{sup +}e{sup -} and di-jet production in hadron-hadron collisions are emphasized.

  9. Characteristics of industrial di(alkylphenyl)dithiophosphoric acids.

    PubMed

    Wittmann, Z; Décsy, Z; Pudmer, E

    1985-01-01

    Instrumental and classical methods have been used to characterize some industrial di(alkylphenyl)dithiophosphoric acids. The (31)P-NMR chemical shifts of di(nonylphenyl)dithiophosphoric acid and its derivatives are summarized.

  10. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  11. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  12. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  13. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  14. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  15. URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS

    EPA Science Inventory

    Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...

  16. Detection of cyclic di-AMP using a competitive ELISA with a unique pneumococcal cyclic di-AMP binding protein

    PubMed Central

    Underwood, Adam J.; Zhang, Yang; Metzger, Dennis W.; Bai, Guangchun

    2014-01-01

    Cyclic di-AMP (c-di-AMP) is a signaling molecule that has been shown to play important roles in bacterial physiology and infections. Currently, c-di-AMP detection and quantification relies mostly on the use of high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS). In this study, a competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of c-di-AMP was developed, which utilizes a novel pneumococcal c-di-AMP binding protein (CabP) and a newly commercialized c-di-AMP derivative. With this new method, c-di-AMP concentrations in biological samples can be quickly and accurately quantified. Furthermore, this assay is much more efficient than current methods as it requires less overall cost and training while processing many samples at once. Therefore, this assay can be extensively used in research into c-di-AMP signaling. PMID:25239824

  17. RTI & DI (Response to Intervention & Differentiated Instruction)

    ERIC Educational Resources Information Center

    Hanson, Helene M.

    2014-01-01

    In today's diverse and inclusive classrooms, teachers face the challenge of delivering instruction that is effective and accessible to students with a wide range of needs, abilities, and learning styles. Newly updated for 2014, "RTI & DI: Response to Intervention & Differentiated Instruction," by Helene Hanson, shows teachers how…

  18. N-Nitroso-di-n-butylamine

    Integrated Risk Information System (IRIS)

    N - Nitroso - di - n - butylamine ; CASRN 924 - 16 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  19. Di (2-ethylhexyl)phthalate (DEHP)

    Integrated Risk Information System (IRIS)

    Di ( 2 - ethylhexyl ) phthalate ( DEHP ) ; CASRN 117 - 81 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessme

  20. Di-hadron production at Jefferson Lab

    SciTech Connect

    Anefalos Pereira, Sergio; et. al.,

    2014-10-01

    Semi-inclusive deep inelastic scattering (SIDIS) has been used extensively in recent years as an important testing ground for QCD. Studies so far have concentrated on better determination of parton distribution functions, distinguishing between the quark and antiquark contributions, and understanding the fragmentation of quarks into hadrons. Hadron pair (di-hadron) SIDIS provides information on the nucleon structure and hadronization dynamics that complement single hadron SIDIS. Di-hadrons allow the study of low- and high-twist distribution functions and Dihadron Fragmentation Functions (DiFF). Together with the twist-2 PDFs ( f1, g1, h1), the Higher Twist (HT) e and hL functions are very interesting because they offer insights into the physics of the largely unexplored quark-gluon correlations, which provide access into the dynamics inside hadrons. The CLAS spectrometer, installed in Hall-B at Jefferson Lab, has collected data using the CEBAF 6 GeV longitudinally polarized electron beam on longitudinally polarized solid NH3 targets. Preliminary results on di-hadron beam-, target- and double-spin asymmetries will be presented.

  1. [Valutazione delle guardie di sicurezza privata attraverso la Suicide Probability Scale e la Brief Symptom Inventory].

    PubMed

    Dogan, Bulent; Canturk, Gurol; Canturk, Nergis; Guney, Sevgi; Özcan, Ebru

    2016-01-01

    RIASSUNTO. Scopo. Lo scopo di questo studio è stato quello di investigare l'influenza della probabilità di suicidio, con le sue caratteristiche sociodemografiche, e di procurare i dati per la prevenzione del suicidio tra le guardie di sicurezza privata che lavorano in condizioni di stress, essendo a contatto ininterrottamente con eventi negativi e traumatici di vita durante il loro lavoro. Metodi. Hanno partecipato allo studio 200 guardie di sicurezza privata e 200 persone dell'Università di Ankara. Per raccogliere i dati sono stati utilizzati un questionario riguardante le condizioni sociodemografiche dei partecipanti, la Suicide Probability Scale (SPS) e la Brief Symptom Inventory (BSI). Risultati. Genere, stato civile, stipendio, credenze religiose, vivere una situazione di pericolo di vita, passato di tentativi di suicidio, fumare e non avere una malattia cronica hanno causato statisticamente una differenza significativa sui punteggi di SPS tra il gruppo di guardie di sicurezza privata e quello di controllo. In aggiunta, c'è stata una correlazione positiva statisticamente significativa tra i punteggi totali delle sottoscale di SPS e quelli di BSI. Conclusioni. Allo stesso modo degli agenti di polizia e dei gendarmi, le guardie di sicurezza privata sono ad alto rischio di commettere e tentare il suicidio trovandosi in condizioni stressanti di lavoro e anche soffrendo del trauma secondario. È necessario che essi siano consapevoli della propria tendenza al suicidio e avere controlli psichiatrici regolari.

  2. [Valutazione delle guardie di sicurezza privata attraverso la Suicide Probability Scale e la Brief Symptom Inventory].

    PubMed

    Dogan, Bulent; Canturk, Gurol; Canturk, Nergis; Guney, Sevgi; Özcan, Ebru

    2016-01-01

    RIASSUNTO. Scopo. Lo scopo di questo studio è stato quello di investigare l'influenza della probabilità di suicidio, con le sue caratteristiche sociodemografiche, e di procurare i dati per la prevenzione del suicidio tra le guardie di sicurezza privata che lavorano in condizioni di stress, essendo a contatto ininterrottamente con eventi negativi e traumatici di vita durante il loro lavoro. Metodi. Hanno partecipato allo studio 200 guardie di sicurezza privata e 200 persone dell'Università di Ankara. Per raccogliere i dati sono stati utilizzati un questionario riguardante le condizioni sociodemografiche dei partecipanti, la Suicide Probability Scale (SPS) e la Brief Symptom Inventory (BSI). Risultati. Genere, stato civile, stipendio, credenze religiose, vivere una situazione di pericolo di vita, passato di tentativi di suicidio, fumare e non avere una malattia cronica hanno causato statisticamente una differenza significativa sui punteggi di SPS tra il gruppo di guardie di sicurezza privata e quello di controllo. In aggiunta, c'è stata una correlazione positiva statisticamente significativa tra i punteggi totali delle sottoscale di SPS e quelli di BSI. Conclusioni. Allo stesso modo degli agenti di polizia e dei gendarmi, le guardie di sicurezza privata sono ad alto rischio di commettere e tentare il suicidio trovandosi in condizioni stressanti di lavoro e anche soffrendo del trauma secondario. È necessario che essi siano consapevoli della propria tendenza al suicidio e avere controlli psichiatrici regolari. PMID:27183512

  3. CYCLIC DI-NUCLEOTIDE SIGNALLING ENTERS THE EUKARYOTE DOMAIN

    PubMed Central

    Schaap, Pauline

    2014-01-01

    SUMMARY Cyclic di-GMP (c-di-GMP) is the prevalent intracellular signalling intermediate in bacteria. It triggers a spectrum of responses that cause bacteria to shift from a swarming motile phase to sessile biofilm formation. However, additional functions for c-di-GMP and roles for related molecules, such as c-di-AMP and c-AMP-GMP continue to be uncovered. The first usage of cyclic-di-nucleotide (c-di-NMP) signalling in the eukaryote domain emerged only recently. In Dictyostelid social amoebas, c-di-GMP is a secreted signal that induces motile amoebas to differentiate into sessile stalk cells. In humans, c-di-NMPs, which are either produced endogenously in response to foreign DNA or by invading bacterial pathogens, trigger the innate immune system by activating the expression of interferon genes. STING, the human c-di-NMP receptor, is conserved throughout metazoa and their closest unicellular relatives, suggesting protist origins for human c-di-NMP signalling. Compared to the limited number of conserved protein domains that detect the second messengers cAMP and cGMP, the domains that detect the c-di-NMPs are surprisingly varied. PMID:24136904

  4. Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms.

    PubMed

    Chou, Shan-Ho; Galperin, Michael Y

    2016-01-01

    Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms.

  5. Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms

    PubMed Central

    2015-01-01

    ABSTRACT Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms. PMID:26055114

  6. Di-interstitial defect in silicon revisited

    SciTech Connect

    Londos, C. A.; Antonaras, G.; Chroneos, A.

    2013-11-21

    Infrared spectroscopy was used to study the defect spectrum of Cz-Si samples following fast neutron irradiation. We mainly focus on the band at 533 cm{sup −1}, which disappears from the spectra at ∼170 °C, exhibiting similar thermal stability with the Si-P6 electron paramagnetic resonance (EPR) spectrum previously correlated with the di-interstitial defect. The suggested structural model of this defect comprises of two self-interstitial atoms located symmetrically around a lattice site Si atom. The band anneals out following a first-order kinetics with an activation energy of 0.88 ± 0.3 eV. This value does not deviate considerably from previously quoted experimental and theoretical values for the di-interstitial defect. The present results indicate that the 533 cm{sup −1} IR band originates from the same structure as that of the Si-P6 EPR spectrum.

  7. Biomaterial based sulphur di oxide gas sensor

    NASA Astrophysics Data System (ADS)

    Ghosh, P. K.; Sarkar, A.

    2013-06-01

    Biomaterials are getting importance in the present research field of sensors. In this present paper performance of biomaterial based gas sensor made of gum Arabica and garlic extract had been studied. Extract of garlic clove with multiple medicinal and chemical utility can be proved to be useful in sensing Sulphur di Oxide gas. On exposure to Sulphur di Oxide gas the material under observation suffers some temporary structural change, which can be observed in form of amplified potentiometric change through simple electronic circuitry. Exploiting this very property a potentiometric gas sensor of faster response and recovery time can be designed. In this work sensing property of the said material has been studied through DC conductance, FTIR spectrum etc.

  8. [Donatori di Musica: when oncology meets music].

    PubMed

    Graiff, Claudio

    2014-10-01

    Donatori di Musica is a network of musicians - both physicians and volunteers - that was initially founded in 2009 with the aim to set up and coordinate classical music concerts in hospitals. This activity was initially started and led by the Oncology Departments at Carrara and Bolzano Hospitals, where high profile professional musicians make themselves available for concerts in support of Oncological in/out-patients of that specific Hospital. A live classical music performance is a deeply touching experience - particularly for those who live a critical condition like cancer. Main characteristics of Donatori di Musica concerts are: continuity (concerts are part of a regular and non-stopping music season); quality (concerts are held by well-established professional musicians); philanthropic attitude (musicians do not wear a suit and usually chat with patients; they also select an easy-to-listen program; a convivial event is usually organized after the performance with the aim of overcoming distinctions and barriers between physician and patient); no profit: musicians perform for free - travel expenses and/or overnight staying only can be claimed; concerts have free access for patients, their families and hospital staff.Patients and musicians therefore do get in close contact and music is able to merge each other experiences - with patients being treated by the beauty of music and musicians being treated theirselves by patients daily-life feedback. The Donatori di Musica experience is therefore able to help Medicine to retrieve its very first significance - the medical act regain that human and cultural dimension that seems to be abandoned in the last decades in favour of a mere technicism. This is the spirit and the deep significance of Donatori di Musica - «[…] the hope that Music can become a key support to medical treatments in every Oncology department» (by Gian Andrea Lodovici).

  9. [Donatori di Musica: when oncology meets music].

    PubMed

    Graiff, Claudio

    2014-10-01

    Donatori di Musica is a network of musicians - both physicians and volunteers - that was initially founded in 2009 with the aim to set up and coordinate classical music concerts in hospitals. This activity was initially started and led by the Oncology Departments at Carrara and Bolzano Hospitals, where high profile professional musicians make themselves available for concerts in support of Oncological in/out-patients of that specific Hospital. A live classical music performance is a deeply touching experience - particularly for those who live a critical condition like cancer. Main characteristics of Donatori di Musica concerts are: continuity (concerts are part of a regular and non-stopping music season); quality (concerts are held by well-established professional musicians); philanthropic attitude (musicians do not wear a suit and usually chat with patients; they also select an easy-to-listen program; a convivial event is usually organized after the performance with the aim of overcoming distinctions and barriers between physician and patient); no profit: musicians perform for free - travel expenses and/or overnight staying only can be claimed; concerts have free access for patients, their families and hospital staff.Patients and musicians therefore do get in close contact and music is able to merge each other experiences - with patients being treated by the beauty of music and musicians being treated theirselves by patients daily-life feedback. The Donatori di Musica experience is therefore able to help Medicine to retrieve its very first significance - the medical act regain that human and cultural dimension that seems to be abandoned in the last decades in favour of a mere technicism. This is the spirit and the deep significance of Donatori di Musica - «[…] the hope that Music can become a key support to medical treatments in every Oncology department» (by Gian Andrea Lodovici). PMID:25282347

  10. [Malattia di Marchiafava-Bignami con coinvolgimento della corteccia frontale e insorgenza tardiva di sintomi psichiatrici resistenti: un caso clinico].

    PubMed

    Gramaglia, Carla; Feggi, Alessandro; Vecchi, Camilla; Di Marco, Sarah; Venesia, Alessandra; Delicato, Claudia; Chieppa, Nunzia; De Marchi, Fabiola; Cantello, Roberto; Zeppegno, Patrizia

    2016-01-01

    RIASSUNTO. Scopo. Descrivere il management di un paziente con malattia di Marchiafava-Bignami (MBD) associata a lesioni frontali corticali, senza sintomi specifici al primo accesso in Pronto Soccorso, e insorgenza tardiva di sintomi psichiatrici atipici. Metodi. Descriviamo il caso di un paziente di 44 anni con storia di abuso cronico di alcol, a cui è stata diagnosticata la MBD. Risultati. La risonanza magnetica ha evidenziato lesioni nello splenio e corpo del corpo calloso e lesioni bilaterali della corteccia frontale. Il paziente ha sviluppato sintomi psichiatrici atipici a insorgenza tardiva, che sono risultati essere resistenti alle terapie farmacologiche impostate. Discussione. Il caso che descriviamo sembra supportare le attuali, ma ancora scarse evidenze che descrivono il coinvolgimento corticale nella MBD, suggerendone l'associazione con una prognosi peggiore. I sintomi psichiatrici possono risultare difficili da trattare a causa della resistenza alle terapie. Conclusione. Il coinvolgimento di psichiatri, radiologi e neurologi secondo un approccio di consultazione-liaison si è dimostrato di fondamentale importanza per la diagnosi e l'impostazione della terapia adeguata al paziente.

  11. Distribution of DI*A and DI*B Allele Frequencies and Comparisons among Central Thai and Other Populations

    PubMed Central

    Nathalang, Oytip; Panichrum, Puangpaka; Intharanut, Kamphon; Thattanon, Phatchira; Nathalang, Siriporn

    2016-01-01

    Alloantibodies to the Diego (DI) blood group system, anti-Dia and anti-Dib are clinically significant in causing hemolytic transfusion reactions (HTRs) and hemolytic disease of the fetus and newborn (HDFN), especially in Asian populations with Mongolian ancestry. This study aimed to report the frequency of the DI*A and DI*B alleles in a Central Thai population and to compare them with those of other populations previously published. Altogether, 1,011 blood samples from unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok were included. Only 391 samples were tested with anti-Dia by conventional tube technique. All samples were genotyped for DI*A and DI*B alleles using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The DI phenotyping and genotyping results were in 100% concordance. The DI*A and DI*B allele frequencies among 1,011 Central Thais were 0.0183 (37/2,022) and 0.9817 (1,985/2,022), respectively. Allele frequencies were compared between Central Thai and other populations. Our data shows that DI*A and DI*B allele frequencies are similar to Southeast Asian, Brazilian, Southern Brazilian and American Native populations; whereas, these frequencies significantly differ from those reported in East Asian, Italian, Alaska Native/Aleut, Hawaiian/Pacific Islander and Filipino populations (P<0.05), corresponding to the results of a matrix of geometric genetic distances. This study confirms that the prevalence of DI*A and DI*B alleles among Central Thais is similar to Southeast Asians and different to others populations of the world. A PCR-based identification of DI genotyping should overcome some of the serological limitations in transfusion medicine and provides a complementary tool for further population-genetic studies. PMID:27764238

  12. Meningococco B: controllo di due focolai epidemici mediante vaccinazione

    PubMed Central

    2014-01-01

    Riassunto La problematica di un efficace approccio vaccinale nei confronti del Meningococco B (MenB) è stata superata identificando con la metodica della "reverse vaccinology" alcuni antigeni capaci di indurre una risposta verso la maggior parte dei ceppi di MenB circolanti nel mondo. Il nuovo vaccino MenB a 4 componenti (4CMenB) è stato autorizzato in Europa, Australia e Canada, ed è entrato nei calendari di immunizzazione pediatrica internazionali: Australia, Canada, UK. In Italia, le prime regioni che hanno raccomandato la vaccinazione contro il MenB sono state Basilicata e Puglia. La gestione di epidemie/focolai epidemici richiede la messa in atto di una risposta rapida da parte delle autorità sanitarie nei confronti di una emergenza sanitaria ad elevato impatto, anche emotivo, sulla popolazione, come recentemente dimostrato in due università americane. Alla dichiarazione di focolaio epidemico in atto, in entrambi i contesti si è attivata una procedura per l'uso del vaccino 4CMenB non ancora autorizzato negli USA. È stato così possibile organizzare gli interventi di profilassi attiva nei due campus universitari, adottando il primo impiego su larga scala del nuovo vaccino 4CMenB e conseguendo, in tempi relativamente brevi, elevati tassi di copertura vaccinale. A fronte di circa 14000 studenti immunizzati con almeno una dose, non è stata segnalata alcuna problematica di eventi avversi conseguenti all'immunizzazione; ad oggi non si sono verificati casi nei soggetti che hanno ricevuto il vaccino. Come conseguenza dei due focolai descritti, è oggi in corso la valutazione da parte dell'FDA per l'estensione dell'uso del vaccino 4CMenB negli Stati Uniti negli adolescenti e giovani adulti. PMID:25916017

  13. Relationship of epigenetic and Dao-di herbs.

    PubMed

    Yuan, Yuan; Wei, Yuan; Yu, Jun; Huang, Lu-qi

    2015-07-01

    Dao-di Herbs is specificity and locality, and its unique phenotypic features is closely related to the growth and development of medicinal plants. In addition to traditional genetic, epigenetic play an important role in formation of Dao-di herbs. This paper introduces the concept of epigenetic and the role of DNA methylation in the gene expression regulation. We further prospects epigenetic mechanism in study of Dao-di herbs formation from specific phenotype and regional analysis. And study on the relationship of epigenetic and Dao-di herbs will provide a basis for quality assessment and identification of Chinese drugs.

  14. Production of aromatics from di- and polyoxygenates

    DOEpatents

    Beck, Taylor; Blank, Brian; Jones, Casey; Woods, Elizabeth; Cortright, Randy

    2016-08-02

    Methods, catalysts, and reactor systems for producing in high yield aromatic chemicals and liquid fuels from a mixture of oxygenates comprising di- and polyoxygenates are disclosed. Also disclosed are methods, catalysts, and reactor systems for producing aromatic chemicals and liquid fuels from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like; and methods, catalysts, and reactor systems for producing the mixture of oxygenates from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like. The disclosed catalysts for preparing the mixture of oxygenates comprise a Ni.sub.nSn.sub.m alloy and a crystalline alumina support.

  15. Production of aromatics from di- and polyoxygenates

    DOEpatents

    Beck, Taylor; Blank, Brian; Jones, Casey; Woods, Elizabeth; Cortright, Randy

    2016-09-13

    Methods, catalysts, and reactor systems for producing in high yield aromatic chemicals and liquid fuels from a mixture of oxygenates comprising di- and polyoxygenates are disclosed. Also disclosed are methods, catalysts, and reactor systems for producing aromatic chemicals and liquid fuels from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like; and methods, catalysts, and reactor systems for producing the mixture of oxygenates from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like. The disclosed catalysts for preparing the mixture of oxygenates comprise a Group VIII metal and a crystalline alumina support.

  16. DiTour 3.1

    SciTech Connect

    Pelaia II, Thomas A.

    2015-06-30

    There is a need for software that allows a tour guide to present different tracks of slides and then return to the default slide show automatically upon completion. A mobile solution is needed for trade shows. DiTour is an iPad/iPhone app that pulls presentation content from a website, stores it on the device and presents it on a connected display. A tour guide can select a track to present and it will automatically return to the default track after a timeout. It offers a mobile solution which is ideal for trade shows.

  17. DiTour 3.1

    2015-06-30

    There is a need for software that allows a tour guide to present different tracks of slides and then return to the default slide show automatically upon completion. A mobile solution is needed for trade shows. DiTour is an iPad/iPhone app that pulls presentation content from a website, stores it on the device and presents it on a connected display. A tour guide can select a track to present and it will automatically return tomore » the default track after a timeout. It offers a mobile solution which is ideal for trade shows.« less

  18. The cyclic di-nucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function

    PubMed Central

    Precit, Mimi; Delince, Matthieu; Pensinger, Daniel; Huynh, TuAnh Ngoc; Jurado, Ashley R.; Goo, Young Ah; Sadilek, Martin; Iavarone, Anthony T.; Sauer, John-Demian; Tong, Liang; Woodward, Joshua J.

    2014-01-01

    SUMMARY Cyclic di-adenosine monophosphate (c-di-AMP) is a broadly conserved second messenger required for bacterial growth and infection. However, the molecular mechanisms of c-di-AMP signaling are still poorly understood. Using a chemical proteomics screen for c-di-AMP interacting proteins in the pathogen Listeria monocytogenes, we identified several broadly conserved protein receptors, including the central metabolic enzyme pyruvate carboxylase (LmPC). Biochemical and crystallographic studies of the LmPC-c-di-AMP interaction revealed a previously unrecognized allosteric regulatory site 25 Å from the active site. Mutations in this site disrupted c-di-AMP binding and affected enzyme catalysis of LmPC as well as PC from pathogenic Enterococcus faecalis. C-di-AMP depletion resulted in altered metabolic activity in L. monocytogenes. Correction of this metabolic imbalance rescued bacterial growth, reduced bacterial lysis, and resulted in enhanced bacterial burdens during infection. These findings greatly expand the c-di-AMP signaling repertoire and reveal a central metabolic regulatory role for a cyclic di-nucleotide. PMID:25215494

  19. Interdisciplinary investigations in support of project DI-MOD

    NASA Technical Reports Server (NTRS)

    Starks, Scott A.

    1991-01-01

    Interdisciplinary investigations in support of project DI-MOD are discussed. The following subject areas were covered: (1) potential extensions of Project DI-MOD to additional sites in Central America; (2) human migration patterns and their impact on malaria transmission; and (3) an investigation into possible computer-based approaches to the analysis of remotely sensed multispectral data.

  20. Synthesis and anticancer activity of di(3-thienyl)methanol and di(3-thienyl)methane.

    PubMed

    Kaushik, Nagendra Kumar; Kim, Hong Seon; Chae, Young June; Lee, Young Nam; Kwon, Gi-Chung; Choi, Eun Ha; Kim, In Tae

    2012-09-27

    Di(3-thienyl)methanol (2) and di(3-thienyl)methane (3) have been synthesized and screened against the T98G (brain cancer) cell line. Treatment induced cell death (MTT and macro-colony assay), growth inhibition, cytogenetic damage (micronuclei formation), were studied as cellular response parameters. Treatment with the compounds enhanced growth inhibition and cell death in a concentration dependent manner in both T98G and HEK (normal) cell lines. At higher concentrations (>20 µg/mL) the cytotoxic effects of the compounds were highly significant. The effect on clonogenic capacity and micronuclei formation observed after treatment of cells. Amongst the compounds, compound 2 exhibited potent activity against T98G brain cancer cells. Despite potent in vitro activity, both compounds exhibited less cytotoxicity against normal human HEK cells at all effective concentrations.

  1. Appunti sulle osservazioni telescopiche di Galilei

    NASA Astrophysics Data System (ADS)

    Vanin, Gabriele

    2001-01-01

    The author inspects the telescopic observations performed by Galileo Galilei beginning since 1609. In the first part he examines the attribution to Galileo of the instruments now in Florence in the Istituto e Museo di Storia della Scienza (IMSS). In the second part he considers the observative and optical analyses realized in this century about the telescopes. In the final part he exposes the observations carried out with an instrument very similar to those Galileo had, the "Project STAR" Scope. The author concludes the IMSS instruments represent very well those used by Galileo and, in particular, they are among the best utilized by Italian scientists. The author is also convinced since 1612 Galileo employed a telescope with 5" resolution power.

  2. Di-photon excess illuminates dark matter

    NASA Astrophysics Data System (ADS)

    Backović, Mihailo; Mariotti, Alberto; Redigolo, Diego

    2016-03-01

    We propose a simplified model of dark matter with a scalar mediator to accommodate the di-photon excess recently observed by the ATLAS and CMS collaborations. Decays of the resonance into dark matter can easily account for a relatively large width of the scalar resonance, while the magnitude of the total width combined with the constraint on dark matter relic density leads to sharp predictions on the parameters of the Dark Sector. Under the assumption of a rather large width, the model predicts a signal consistent with ˜ 300 GeV dark matter particle and ˜ 750 GeV scalar mediator in channels with large missing energy. This prediction is not yet severely bounded by LHC Run I searches and will be accessible at the LHC Run II in the jet plus missing energy channel with more luminosity. Our analysis also considers astro-physical constraints, pointing out that future direct detection experiments will be sensitive to this scenario.

  3. ParaDiS-FEM dislocation dynamics simulation code primer

    SciTech Connect

    Tang, M; Hommes, G; Aubry, S; Arsenlis, A

    2011-09-27

    The ParaDiS code is developed to study bulk systems with periodic boundary conditions. When we try to perform discrete dislocation dynamics simulations for finite systems such as thin films or cylinders, the ParaDiS code must be extended. First, dislocations need to be contained inside the finite simulation box; Second, dislocations inside the finite box experience image stresses due to the free surfaces. We have developed in-house FEM subroutines to couple with the ParaDiS code to deal with free surface related issues in the dislocation dynamics simulations. This primer explains how the coupled code was developed, the main changes from the ParaDiS code, and the functions of the new FEM subroutines.

  4. Upper limb malformations in DiGeorge syndrome

    SciTech Connect

    Cormier-Daire, V.; Iserin, L.; Sidi, D.

    1995-03-13

    We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

  5. Di-photon resonance and Dark Matter as heavy pions

    NASA Astrophysics Data System (ADS)

    Redi, Michele; Strumia, Alessandro; Tesi, Andrea; Vigiani, Elena

    2016-05-01

    We analyse confining gauge theories where the 750 GeV di-photon resonance is a composite techni-pion that undergoes anomalous decays into SM vectors. These scenarios naturally contain accidentally stable techni-pions Dark Matter candidates. The di-photon resonance can acquire a larger width by decaying into Dark Matter through the CP-violating θ-term of the new gauge theory reproducing the cosmological Dark Matter density as a thermal relic.

  6. Synthesis, physicochemical, and tribological characterization of S-Di-n-octoxyboron-O,O'-di-n-octyldithiophosphate.

    PubMed

    Shah, Faiz Ullah; Glavatskih, Sergei; Antzutkin, Oleg N

    2009-12-01

    Dialkyldithiophosphates (DTPs) of zinc(II), copper(II), and other metals have been extensively used as multifunctional additives in lubricants to control friction and reduce wear in mechanical systems. Among these DTP compounds, zinc dialkyldithiophosphates (ZnDTPs) are the most common additives extensively used for more than 60 years. These additives form a protective film on steel surfaces and, thus, control friction and reduce wear. However, ZnDTPs contain zinc and large amounts of phosphorus and sulfur, which impair the environment, both directly and indirectly, by adversely affecting the performance of catalytic converters of various automobiles. For this reason, environmental legislation imposes limitations on concentrations of phosphorus, sulfur, and zinc in the lubricants. In this work, we report on zinc-free S-di-n-octoxyboron-O,O'-di-n-octyldithiophosphate (DOB-DTP) lubricant additive with amount of phosphorus and sulfur reduced by half in a molecule as compared with ZnDTPs. DOB-DTP was synthesized by a reaction in two steps under inert nitrogen atmosphere. The final product, a viscous liquid, was characterized by the elemental analysis, FT-IR, multinuclear (1)H, (13)C, (31)P, and (11)B NMR spectroscopy and thermal analyses. Tribological performance of a mineral oil with this new additive was evaluated in comparison with O,O'-di-n-butyl-dithiophosphato-zinc(II) (ZnDTP) using a four-ball tribometer. The surface morphology and the elemental composition of the tribofilms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS). The results show that DOB-DTP has a considerably better antiwear performance and higher stability of the coefficient of friction with time as compared with ZnDTP. Both phosphorus and sulfur were detected by the EDS on the worn steel surfaces at all concentrations of additives in the base oil.

  7. Biofilms and Cyclic di-GMP (c-di-GMP) Signaling: Lessons from Pseudomonas aeruginosa and Other Bacteria*

    PubMed Central

    Valentini, Martina

    2016-01-01

    The cyclic di-GMP (c-di-GMP) second messenger represents a signaling system that regulates many bacterial behaviors and is of key importance for driving the lifestyle switch between motile loner cells and biofilm formers. This review provides an up-to-date compendium of c-di-GMP pathways connected to biofilm formation, biofilm-associated motilities, and other functionalities in the ubiquitous and opportunistic human pathogen Pseudomonas aeruginosa. This bacterium is frequently adopted as a model organism to study bacterial biofilm formation. Importantly, its versatility and adaptation capabilities are linked with a broad range of complex regulatory networks, including a large set of genes involved in c-di-GMP biosynthesis, degradation, and transmission. PMID:27129226

  8. Biofilms and Cyclic di-GMP (c-di-GMP) Signaling: Lessons from Pseudomonas aeruginosa and Other Bacteria.

    PubMed

    Valentini, Martina; Filloux, Alain

    2016-06-10

    The cyclic di-GMP (c-di-GMP) second messenger represents a signaling system that regulates many bacterial behaviors and is of key importance for driving the lifestyle switch between motile loner cells and biofilm formers. This review provides an up-to-date compendium of c-di-GMP pathways connected to biofilm formation, biofilm-associated motilities, and other functionalities in the ubiquitous and opportunistic human pathogen Pseudomonas aeruginosa This bacterium is frequently adopted as a model organism to study bacterial biofilm formation. Importantly, its versatility and adaptation capabilities are linked with a broad range of complex regulatory networks, including a large set of genes involved in c-di-GMP biosynthesis, degradation, and transmission.

  9. Developmental toxicity of di-isodecyl and di-isononyl phthalates in rats.

    PubMed

    Waterman, S J; Ambroso, J L; Keller, L H; Trimmer, G W; Nikiforov, A I; Harris, S B

    1999-01-01

    The developmental toxicity of di-isodecyl phthalate (DIDP; CAS RN 68515-49-1) and di-isononyl phthalate (DINP; CAS RN 68515-48-0) were investigated in Sprague-Dawley rats. DIDP and DINP were administered by gavage to mated rats at doses of 0, 100, 500, and 1000 mg/kg/d on Gestation Days (GD) 6 through 15. Cesarean sections were performed on GD 21 and the fetuses removed for evaluation. Maternal weight gain and food consumption were significantly reduced at 1000 mg/kg/d during the exposure period. No treatment-related effects were noted at cesarean section, nor were there any fetal morphologic observations except for an increased frequency of seventh cervical and rudimentary lumbar ribs at the maternally toxic exposure level of 1000 mg/kg/d. Under these study conditions, mild maternal and developmental effects were observed at 1000 mg/kg/d. Both maternal and developmental NOAELs were therefore established at 500 mg/kg/d. The results indicate that neither DIDP nor DINP is teratogenic or a selective developmental toxicant.

  10. Cyclic Di-AMP Homeostasis in Bacillus subtilis

    PubMed Central

    Mehne, Felix M. P.; Gunka, Katrin; Eilers, Hinnerk; Herzberg, Christina; Kaever, Volkhard; Stülke, Jörg

    2013-01-01

    The genome of the Gram-positive soil bacterium Bacillus subtilis encodes three potential diadenylate cyclases that may synthesize the signaling nucleotide cyclic di-AMP (c-di-AMP). These enzymes are expressed under different conditions in different cell compartments, and they localize to distinct positions in the cell. Here we demonstrate the diadenylate cyclase activity of the so far uncharacterized enzymes CdaA (previously known as YbbP) and CdaS (YojJ). Our work confirms that c-di-AMP is essential for the growth of B. subtilis and shows that an excess of the molecule is also harmful for the bacteria. Several lines of evidence suggest that the diadenylate cyclase CdaA is part of the conserved essential cda-glm module involved in cell wall metabolism. In contrast, the CdaS enzyme seems to provide c-di-AMP for spores. Accumulation of large amounts of c-di-AMP impairs the growth of B. subtilis and results in the formation of aberrant curly cells. This phenotype can be partially suppressed by elevated concentrations of magnesium. These observations suggest that c-di-AMP interferes with the peptidoglycan synthesis machinery. The activity of the diadenylate cyclases is controlled by distinct molecular mechanisms. CdaA is stimulated by a regulatory interaction with the CdaR (YbbR) protein. In contrast, the activity of CdaS seems to be intrinsically restricted, and a single amino acid substitution is sufficient to drastically increase the activity of the enzyme. Taken together, our results support the idea of an important role for c-di-AMP in B. subtilis and suggest that the levels of the nucleotide have to be tightly controlled. PMID:23192352

  11. Diffractive interference optical analyzer (DiOPTER)

    NASA Astrophysics Data System (ADS)

    Sasikumar, Harish; Prasad, Vishnu; Pal, Parama; Varma, Manoj M.

    2016-03-01

    This report demonstrates a method for high-resolution refractometric measurements using, what we have termed as, a Diffractive Interference Optical Analyzer (DiOpter). The setup consists of a laser, polarizer, a transparent diffraction grating and Si-photodetectors. The sensor is based on the differential response of diffracted orders to bulk refractive index changes. In these setups, the differential read-out of the diffracted orders suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6x10-7 RIU was achieved in glass. This work focuses on devices with integrated sample well, made on low-cost PDMS. As the detection methodology is experimentally straightforward, it can be used across a wide array of applications, ranging from detecting changes in surface adsorbates via binding reactions to estimating refractive index (and hence concentration) variations in bulk samples. An exciting prospect of this technique is the potential integration of this device to smartphones using a simple interface based on transmission mode configuration. In a transmission configuration, we were able to achieve an LoD of 4x10-4 RIU which is sufficient to explore several applications in food quality testing and related fields. We are envisioning the future of this platform as a personal handheld optical analyzer for applications ranging from environmental sensing to healthcare and quality testing of food products.

  12. Optimization of RNA-based c-di-GMP fluorescent sensors through tuning their structural modules.

    PubMed

    Inuzuka, Saki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2016-08-01

    Cyclic diguanylate (c-di-GMP) is a second messenger of bacteria and its detection is an important issue in basic and applied microbiology. As c-di-GMP riboswitch ligand-binding domains (aptamer domains) capture c-di-GMP with high affinity and selectivity, they are promising platforms for the development of RNA-based c-di-GMP sensors. We analyzed two previously reported c-di-GMP sensor RNAs derived from the Vc2 riboswitch. We also designed and tested their variants, some of which showed improved properties as RNA-based c-di-GMP sensors.

  13. Putting a stop to di-Higgs modifications

    NASA Astrophysics Data System (ADS)

    Batell, Brian; McCullough, Matthew; Stolarski, Daniel; Verhaaren, Christopher B.

    2015-09-01

    Pair production of Higgs bosons at hadron colliders is an enticing channel to search for new physics. New colored particles that couple strongly to the Higgs, such as those most often called upon to address the hierarchy problem, provide well motivated examples in which large enhancements of the di-Higgs rate are possible, at least in principle. However, in such scenarios the di-Higgs production rate is tightly correlated with the single Higgs production rate and, since the latter is observed to be SM-like, one generally expects that only modest enhancements in di-Higgs production are allowed by the LHC Run 1 data. We examine the contribution of top squarks (stops) in a simplified supersymmetry model to di-Higgs production and find that this general expectation is indeed borne out. In particular, the allowed deviations are typically small, but there are tuned regions of parameter space where expectations based on EFT arguments break down in which O(100%) enhancements to the di-Higgs production rate are possible and are simultaneously consistent with the observed single Higgs production rates. These effects are potentially observable with the high luminosity run of the LHC or at a future hadron collider.

  14. Analysis of lustred ceramics of the Galleria Regionale di Palazzo Bellomo di Siracusa, Italy

    NASA Astrophysics Data System (ADS)

    Politi, Giuseppe; Bouquillon, Anne; Aucouturier, Marc; Gueli, Anna; Troja, Sebastiano Olindo; Vella, Carmela; Pacheco, Claire; Pichon, Laurent; Moignard, Brice; Lemasson, Quentin

    2014-07-01

    Several fragments of lustred pottery coming from the collection of the Galleria Regionale di Palazzo Bellomo and excavated in Siracusa, were studied through non-invasive ion beam techniques in the Centre de Recherche et de Restauration des Musees de France in Paris. Up to now only aesthetic and stylistic analysis were available for these objects, and their provenances and dating were unknown or uncertain; moreover, the question concerning a possible local production was still debated. Compositions of pottery and glazed parts were thus obtained by Particle Induced X-ray Emission analysis, while the depth distribution of element of the lustre was analyzed by the Rutherford Backscattering Spectrometry technique. The obtained results provided important information on possible origin and production period of the objects.

  15. Luminescence properties of dysprosium doped di-calcium di-aluminium silicate phosphors

    NASA Astrophysics Data System (ADS)

    Tiwari, Geetanjali; Brahme, Nameeta; Sharma, Ravi; Bisen, D. P.; Sao, Sanjay K.; Tigga, Shalinta

    2016-08-01

    A Dysprosium doped di-calcium di-aluminium silicate phosphor emitting long-lasting white light was prepared and investigated. Phosphors were synthesized by combustion-assisted method. The effect of doping concentration on the crystal structure and luminescence properties of Ca2Al2SiO7:Dy3+ phosphors were investigated. The phase structure, surface morphology, particle size, elemental analysis was analyzed by using X-ray diffraction (XRD), transmission electron microscope (TEM), Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX) techniques. X-ray diffraction (XRD) profiles showed that all peaks could be attributed to the tetragonal Ca2Al2SiO7 phase when the sample was annealed at 1100 °C. The increase in TL intensity indicates that the concentration of traps increases with UV irradiation. Under the UV-excitation, the Thermoluminescence (TL) emission spectra of Ca2Al2SiO7:Dy3+ phosphor shows the characteristic emission of Dy3+ peaking at 484 nm (blue), 583 nm (yellow) and 680 nm (red), originating from the transitions of 4F9/2 → 6H15/2, 4F9/2 → 6H13/2 and 4F9/2 → 6H11/2. Photoluminescence (PL) decay has also reported and it indicates that Ca2Al2SiO7:Dy3+ phosphor contains fast decay and slow decay process. The peak of Mechanoluminescence (ML) intensity increases linearly with increasing impact velocity of the moving piston. The possible mechanism of Thermoluminescence (TL), Photoluminescence (PL) and Mechanoluminescence (ML) of this white light emitting long lasting phosphor is also investigated.

  16. DiProDB: a database for dinucleotide properties.

    PubMed

    Friedel, Maik; Nikolajewa, Swetlana; Sühnel, Jürgen; Wilhelm, Thomas

    2009-01-01

    DiProDB (http://diprodb.fli-leibniz.de) is a database of conformational and thermodynamic dinucleotide properties. It includes datasets both for DNA and RNA, as well as for single and double strands. The data have been shown to be important for understanding different aspects of nucleic acid structure and function, and they can also be used for encoding nucleic acid sequences. The database is intended to facilitate further applications of dinucleotide properties. A number of property datasets is highly correlated. Therefore, the database comes with a correlation analysis facility. Authors having determined new sets of dinucleotide property values are invited to submit these data to DiProDB.

  17. Target Search and Selection for the DI/EPOXI Spacecraft

    NASA Technical Reports Server (NTRS)

    Grebow, Daniel J.; Bhaskaran, Shyam; Chesley, Steven R.

    2012-01-01

    Upon completion of the Hartley 2 flyby in November 2010, the Deep Impact (DI) spacecraft resided in a solar orbit without possibility for gravity assist with any large body. Conservative estimates of remaining fuel were enough to provide only an 18 m/s impulse on the spacecraft. We present our method and results of our systematic scan of potential small body encounters for DI, and our criteria to narrow the selection to the asteroid 2002 GT as the target flyby body. The mission profile has two deterministic maneuvers to achieve the encounter, the first of which executed on November 25, 2011.

  18. Target Search & Selection for the DI/EPOXI Spacecraft

    NASA Technical Reports Server (NTRS)

    Grebow, Daniel J.; Bhaskaran, Shyam; Chesley, Steven R.

    2012-01-01

    Upon completion of the Hartley 2 flyby in November 2010, the Deep Impact (DI) spacecraft resided in a solar orbit without possibility for gravity assist with any large body. Conservative estimates of remaining fuel were enough to provide only an 18 m/s impulse on the spacecraft. We present our method and results of our systematic scan of potential small body encounters for DI, and our criteria to narrow the selection to the asteroid 2002 GT as the target flyby body. The mission profile has two deterministic maneuvers to achieve the encounter, the first of which executed on November 25, 2011.

  19. Carbon dioxide emissions from Specchio di Venere, Pantelleria, Italy

    NASA Astrophysics Data System (ADS)

    Paz, Mariana P. Jácome; Inguaggiato, Salvatore; Taran, Yuri; Vita, Fabio; Pecoraino, Giovanella

    2016-04-01

    We have mapped the diffuse CO2 efflux from the Specchio di Venere Lake area using the accumulation chamber method. We calculated a CO2 emission of 43 ± 5 t day-1 for the area studied, accounting for both diffuse degassing from soil and bubbling through the lake. We also present data on the water composition of Specchio di Venere Lake, the Polla 3 spring, and Liuzza well. On the basis of water chemistry, two physical-chemical processes, evaporation and mineral precipitation of carbonate species, are invoked to explain the CO2 degassing for the lake area.

  20. [I costi farmacologici della terapia di conversione con farmaci biologici nel carcinoma del colon-retto con metastasi epatiche].

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2016-08-01

    Riassunto. Lo scopo di questo studio è quello di valutare i costi dei farmaci (con particolare riferimento alle terapie con farmaci biologici) utilizzati nella terapia di conversione in una popolazione non selezionata di pazienti affetti da carcinoma del colon-retto in stadio avanzato, al fine di ottenere una resezione epatica R0. In questa rassegna sono stati selezionati i report completi e gli aggiornamenti di tutti gli studi clinici randomizzati (di fase II e fase III) che confrontassero almeno 2 regimi di terapia con farmaci biologici in prima linea in pazienti affetti da carcinoma del colon-retto in stadio avanzato di malattia. I costi dei farmaci sono stati ricavati dalla nostra Farmacia Ospedaliera e sono espressi in euro (€). Il nostro studio inizia con la valutazione di 683 abstract. 48 tria sono stati considerati adeguati per una successiva analisi. Una valutazione più approfondita ha portato all'esclusione di 37 trial, lasciando alla valutazione finale 11 studi clinici randomizzati (3 trial di fase II, per un totale di 522 pazienti, e 8 studi di fase III, per un totale di 7191 pazienti). I costi dei farmaci utilizzati nella terapia di conversione aumentano con la sostituzione del 5-fluorouracile con la capecitabina e, in misura maggiore, con l'introduzione degli agenti biologici. In questo lavoro sono presentati due punti chiave. Primo, i costi degli agenti farmacologici utilizzati nei regimi di prima linea a base di agenti biologici più comunemente utilizzati nel trattamento del carcinoma del colon-retto in stadio avanzato sono molto variabili. Secondo, i dati di efficacia dei regimi pubblicati, in termini di tassi di resezione, dipendono dalla selezione dei pazienti, dalle caratteristiche del tumore e dal tipo di schema di terapia.

  1. [I costi farmacologici della terapia di conversione con farmaci biologici nel carcinoma del colon-retto con metastasi epatiche].

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2016-08-01

    Riassunto. Lo scopo di questo studio è quello di valutare i costi dei farmaci (con particolare riferimento alle terapie con farmaci biologici) utilizzati nella terapia di conversione in una popolazione non selezionata di pazienti affetti da carcinoma del colon-retto in stadio avanzato, al fine di ottenere una resezione epatica R0. In questa rassegna sono stati selezionati i report completi e gli aggiornamenti di tutti gli studi clinici randomizzati (di fase II e fase III) che confrontassero almeno 2 regimi di terapia con farmaci biologici in prima linea in pazienti affetti da carcinoma del colon-retto in stadio avanzato di malattia. I costi dei farmaci sono stati ricavati dalla nostra Farmacia Ospedaliera e sono espressi in euro (€). Il nostro studio inizia con la valutazione di 683 abstract. 48 tria sono stati considerati adeguati per una successiva analisi. Una valutazione più approfondita ha portato all'esclusione di 37 trial, lasciando alla valutazione finale 11 studi clinici randomizzati (3 trial di fase II, per un totale di 522 pazienti, e 8 studi di fase III, per un totale di 7191 pazienti). I costi dei farmaci utilizzati nella terapia di conversione aumentano con la sostituzione del 5-fluorouracile con la capecitabina e, in misura maggiore, con l'introduzione degli agenti biologici. In questo lavoro sono presentati due punti chiave. Primo, i costi degli agenti farmacologici utilizzati nei regimi di prima linea a base di agenti biologici più comunemente utilizzati nel trattamento del carcinoma del colon-retto in stadio avanzato sono molto variabili. Secondo, i dati di efficacia dei regimi pubblicati, in termini di tassi di resezione, dipendono dalla selezione dei pazienti, dalle caratteristiche del tumore e dal tipo di schema di terapia. PMID:27571559

  2. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting...

  3. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting...

  4. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting...

  5. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting...

  6. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting...

  7. 40 CFR 721.10261 - Oxime, di-Me silane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN...

  8. 40 CFR 721.10261 - Oxime, di-Me silane (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN...

  9. 40 CFR 721.10261 - Oxime, di-Me silane (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN...

  10. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  11. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES.

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  12. Synthesis and Chemistry of Organic Geminal Di- and Triazides.

    PubMed

    Häring, Andreas P; Kirsch, Stefan F

    2015-11-06

    This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections.

  13. 10 Tips for Turning DI Theory into Practice

    ERIC Educational Resources Information Center

    Ducey, Melissa N.; Key, Shirley

    2009-01-01

    At the core of differentiated instruction (DI) is the belief that because all children are different, their learning needs and abilities are different, and therefore must be approached differently. Differentiating instruction allows teachers to meet the students where they are academically and bring them forward. Although one continues to grow in…

  14. The metabolism of di-(3,5-di-tert.-butyl-4-hydroxybenzyl) ether (Ionox 201) in the rat.

    PubMed

    Wright, A S; Crowne, R S; Hathway, D E

    1967-01-01

    1. Up to one-third of a single oral dose of Ionox 201 was absorbed in rats. 2. In rats dosed with [(14)C]Ionox 201 86.8-97.2% of the label is excreted in the faeces in 24 days (much of this is eliminated in the first 4 days after dosage), 5.6% in the urine and not more than 0.8% in the exhaled air; 5.0% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 3. About 65.0% of (14)C in the faeces is due to unchanged antioxidant, 30.0% to 3,5-di-tert.-butyl-4-hydroxybenzoic acid, 3.5% to unidentified polar constituent(s), 1.4% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde and 0.1% to 3,3',5,5'-tetra-tert.-butyl-4-,4'-stilbenequinone. A variable proportion of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid (40-60%) and the remainder (60-40%) to the ester glucuronide, when the animals were treated with different doses of antioxidant. In eight individual animals dosed with 6.78mg. of [(14)C]Ionox 201, one-third of (14)C in the bile is due to the free acid, 45% to the ester glucuronide, 20% to an unidentified constituent and 2% to unchanged antioxidant, and, in two animals dosed with 13.56mg., there is a small proportion of free acid and a larger proportion of ester glucuronide. About 80% of (14)C in the body fat is due to unchanged antioxidant, 19% to the free acid and 1% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde. 4. At least 36.2% of a single oral dose of Ionox 201 is metabolized: 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 30.2% of a dose, (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 1.4%, 3,5-di-tert.-butyl-4-hydroxybenzaldehyde for 1.3%, 3,3',5,5'-tetra-tert.-butyl-4,4'-stilbenequinone for 0.1% and unidentified polar metabolite(s) for 3.2%. 5. The metabolism of Ionox 201 in vivo is closely related to its antioxidant action in vitro. PMID:6030293

  15. The metabolism of di-(3,5-di-tert.-butyl-4-hydroxybenzyl) ether (Ionox 201) in the rat

    PubMed Central

    Wright, A. S.; Crowne, R. S.; Hathway, D. E.

    1967-01-01

    1. Up to one-third of a single oral dose of Ionox 201 was absorbed in rats. 2. In rats dosed with [14C]Ionox 201 86·8–97·2% of the label is excreted in the faeces in 24 days (much of this is eliminated in the first 4 days after dosage), 5·6% in the urine and not more than 0·8% in the exhaled air; 5·0% of 14C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 3. About 65·0% of 14C in the faeces is due to unchanged antioxidant, 30·0% to 3,5-di-tert.-butyl-4-hydroxybenzoic acid, 3·5% to unidentified polar constituent(s), 1·4% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde and 0·1% to 3,3′,5,5′-tetra-tert.-butyl-4-,4′-stilbenequinone. A variable proportion of 14C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid (40–60%) and the remainder (60–40%) to the ester glucuronide, when the animals were treated with different doses of antioxidant. In eight individual animals dosed with 6·78mg. of [14C]Ionox 201, one-third of 14C in the bile is due to the free acid, 45% to the ester glucuronide, 20% to an unidentified constituent and 2% to unchanged antioxidant, and, in two animals dosed with 13·56mg., there is a small proportion of free acid and a larger proportion of ester glucuronide. About 80% of 14C in the body fat is due to unchanged antioxidant, 19% to the free acid and 1% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde. 4. At least 36·2% of a single oral dose of Ionox 201 is metabolized: 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 30·2% of a dose, (3,5-di-tert.-butyl-4-hydroxybenzoyl β-d-glucopyranosid)uronic acid for 1·4%, 3,5-di-tert.-butyl-4-hydroxybenzaldehyde for 1·3%, 3,3′,5,5′-tetra-tert.-butyl-4,4′-stilbenequinone for 0·1% and unidentified polar metabolite(s) for 3·2%. 5. The metabolism of Ionox 201 in vivo is closely related to its antioxidant action in vitro. PMID:6030293

  16. Improved critical current density in DI-BSCCO

    NASA Astrophysics Data System (ADS)

    Ayai, N.; Kikuchi, M.; Tatamidani, K.; Nakashima, T.; Osabe, G.; Kagiyama, T.; Fujikami, J.; Kobayashi, S.; Yamazaki, K.; Yamade, S.; Shizuya, E.; Hayashi, K.; Sato, K.; Kiss, T.; Higashikawa, K.; Inoue, M.; Kitaguchi, H.; Kumakura, H.; Shimoyama, J.

    2010-06-01

    High Ic in DI-BSCCO has been demonstrated even in high temperature up to 90K and parallel magnetic field up to 200 mT. This performance is advantageous especially to power cables cooled with pressurized liquid nitrogen, where current and temperature fluctuates in real operation. Recent development has updated the highest Jc at 77K, self-field to 630 A/mm2 in a R&D tape. The evaluation by a scanning magnetic microscope has demonstrated the highest Jc of 900 A/mm2 at the midst of a tape which has Ic of 200 A. This property promises innovative Ic more than 300 A in future DI-BSCCO.

  17. [The Istituto di Storia della Medicina archive and video collection].

    PubMed

    Aruta, Alessandro; De Angelis, Elio

    2006-01-01

    The Istituto di Storia della Medicina at Rome University was to a certain extent a one-man achievement. Founded by Adalberto Pazzini in 1937, its collections comprehended books, objects, as well as photographs, movies, and other didactic video. The Istituto was also a center for publications, conferences and meetings. The archival sources that document its activity have been re-evaluated and restored in recent years, together with the collections housed in the Library and in the Museum.

  18. The di-heme family of respiratory complex II enzymes.

    PubMed

    Lancaster, C Roy D

    2013-05-01

    The di-heme family of succinate:quinone oxidoreductases is of particular interest, because its members support electron transfer across the biological membranes in which they are embedded. In the case of the di-heme-containing succinate:menaquinone reductase (SQR) from Gram-positive bacteria and other menaquinone-containing bacteria, this results in an electrogenic reaction. This is physiologically relevant in that it allows the transmembrane electrochemical proton potential Δp to drive the endergonic oxidation of succinate by menaquinone. In the case of the reverse reaction, menaquinol oxidation by fumarate, catalysed by the di-heme-containing quinol:fumarate reductase (QFR), evidence has been obtained that this electrogenic electron transfer reaction is compensated by proton transfer via a both novel and essential transmembrane proton transfer pathway ("E-pathway"). Although the reduction of fumarate by menaquinol is exergonic, it is obviously not exergonic enough to support the generation of a Δp. This compensatory "E-pathway" appears to be required by all di-heme-containing QFR enzymes and results in the overall reaction being electroneutral. In addition to giving a brief overview of progress in the characterization of other members of this diverse family, this contribution summarizes key evidence and progress in identifying constituents of the "E-pathway" within the framework of the crystal structure of the QFR from the anaerobic epsilon-proteobacterium Wolinella succinogenes at 1.78Å resolution. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

  19. URINARY AND AMNIOTIC FLUID LEVELS OF PHTHALATE MONOESTERS IN RATS AFTER THE ORAL ADMINISTRATION OF DI(2-ETHYLHEXYL) PHTHALATE AND DI-N-BUTYL PHTHALATE

    EPA Science Inventory

    Two studies were designed to examine amniotic fluid and maternal urine concentrations of the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethylhexyl) phthalate (MEHP) and the di-n-butyl phthalate (DBP) metabolite monobutyl phthalate (MBP) after administration of DEHP and D...

  20. Di-n-butyl Phthalate (DNBP) and Diisobutyl Phthalate (DiBP) Metabolism in a Human Volunteer after Single Oral Doses [Journal Article

    EPA Science Inventory

    An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...

  1. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721..., reaction products with 3-(triethoxysilyl)-1-propanamine. (a) Chemical substance and significant new uses..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine (PMN...

  2. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721..., reaction products with 3-(triethoxysilyl)-1-propanamine. (a) Chemical substance and significant new uses..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine (PMN...

  3. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721..., reaction products with 3-(triethoxysilyl)-1-propanamine. (a) Chemical substance and significant new uses..., polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine (PMN...

  4. DiGeorge syndrome with vertebral and rib dysplasia

    SciTech Connect

    Puno-Cocuzza, C.; David, K.; Kogekar, N.

    1994-09-01

    DiGeorge syndrome results from defect in the development of the third and fourth pharyngeal pouches, and is characterized by conotruncal heart defects, aplasia or hypoplasia of thymus and parathyroid glands resulting in immune deficiency and hypocalcemia. Other associated abnormalities include renal, thyroid and diaphragmatic defects, oral clefting, etc. Etiologically, it is heterogeneous, with a microdeletion of 22q11 present in over 80% of cases. Our patient was born following a pregnancy complicated by insulin dependent gestational diabetes. There was truncus arteriosus type 2, absense of thymic shadow on CXR with severe deficiency of T cell function, and persistent hypocalcemia with low parathormone. Right kidney was absent. Dysplastic ribs including fused and bifid ribs were noted. Hypoplastic vertebrae and hemivertebrae were present through thoracic and lumbar regions. Chromosome analysis was normal, and metaphase FISH analysis with probe N25 representing locus D22S75 did not show any deletion of 22q11.2. The skeletal findings similar to these have not been previously reported in association with DiGeorge syndrome to our knowledge. Vertebral and rib abnormalities are known to occur with pregestational maternal diabetes. Maternal diabetes has also been suggested to be a possible etiology in a very small proportion of DiGeorge syndrome cases. It is possible that these findings occured together on account of gestational maternal diabetes in our case.

  5. Mono- and di-cationic hydrido boron compounds.

    PubMed

    Ghadwal, Rajendra S; Schürmann, Christian J; Andrada, Diego M; Frenking, Gernot

    2015-08-28

    Brønsted acid HNTf2 (Tf = SO2CF3) mediated dehydrogenative hydride abstraction from (L(1))BH3 () and (L(2))BH3 () (L(1) = IPrCH2 = 1,3-(2,6-di-isopropylphenyl)imidazol-2-methylidene (); L(2) = SIPrCH2 = 1,3-(2,6-di-isopropylphenyl)imidazolidin-2-methylidiene ()) affords thermally stable hydride bridged mono-cationic hydrido boron compounds [{(L(1))BH2}2(μ-H)](NTf2) () and [{(L(2))BH2}2(μ-H)](NTf2) (). Furthermore, hydride abstraction yields di-cationic hydrido boron compounds [{(L(1))BH}2(μ-H)2](NTf2)2 () and [{(L(2))BH}2(μ-H)2](NTf2)2 (). Unique cationic boron compounds with CH2BH2(μ-H)BH2CH2 ( and ) and CH2BH(μ-H)2BHCH2 ( and ) moieties feature a 3c-2e bond and have been fully characterized. Interesting electronic and structural features of compounds are analysed using spectroscopic, crystallographic, and computational methods. PMID:26200103

  6. Complexation of di-amides of dipicolinic acid with neodymium

    SciTech Connect

    Lapka, J.L.; Paulenova, A.

    2013-07-01

    Di-amides have undergone significant studies as possible ligands for use in the partitioning of trivalent minor actinides and lanthanides. The binding affinities of three isomeric ligands with neodymium in acetonitrile solution have been investigated. The stability constants of the metal-ligand complexes formed between different isomers of N,N'-diethyl-N,N'- ditolyl-di-picolinamide (EtTDPA) and trivalent neodymium in acetonitrile have been determined by spectrophotometric and calorimetric methods. Each isomer of EtTDPA has been found to be capable of forming three complexes with trivalent neodymium, Nd(EtTDPA), Nd(EtTDPA){sub 2}, and Nd(EtTDPA){sub 3}. Values from spectrophotometric and calorimetric titrations are within reasonable agreement with each other. The order of stability constants for each metal:ligand complex decreases in the order Et(m)TDPA > Et(p)TDPA > Et(o)TDPA. The obtained values are comparable to other di-amidic ligands obtained under similar system conditions and mirror previously obtained solvent extraction data for EtTDPA at low ionic strengths. (authors.

  7. Di(hydroxyphenyl)- 1,2,4-triazole monomers

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

    1993-01-01

    The di(hydroxyphenyl)- 1,2,4-triazole monomers were first synthesized by reacting bis (4-hydroxyphenyl) hydrazide with aniline hydrochloride at 250 C in the melt and also by reacting 1,3 or 1,4-bis- (4-hydroxyphenyl)- phenylene- dihydrazide with 2 moles of aniline hydrochloride in the melt. Purification of the di(hydroxyphenyl)- 1,2,4-triazole monomers was accomplished by recrystallization. Poly (1,2,4-triazoles) (PT) were prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)- 1,2,4-triazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions were carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. This synthetic route has provided high molecular weight PT of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides.

  8. Endo-S-c-di-GMP analogues-polymorphism and binding studies with class I riboswitch.

    PubMed

    Zhou, Jie; Sayre, David A; Wang, Jingxin; Pahadi, Nirmal; Sintim, Herman O

    2012-01-01

    C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues). We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering). Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch. PMID:23143150

  9. c-di-GMP and its Effects on Biofilm Formation and Dispersion: a Pseudomonas Aeruginosa Review.

    PubMed

    Ha, Dae-Gon; O'Toole, George A

    2015-04-01

    Since its initial discovery as an allosteric factor regulating cellulose biosynthesis in Gluconacetobacter xylinus, the list of functional outputs regulated by c-di-GMP has grown. We have focused this article on one of these c-di-GMP-regulated processes, namely, biofilm formation in the organism Pseudomonas aeruginosa. The majority of diguanylate cyclases and phosphodiesterases encoded in the P. aeruginosa genome still remain uncharacterized; thus, there is still a great deal to be learned about the link between c-di-GMP and biofilm formation in this microbe. In particular, while a number of c-di-GMP metabolizing enzymes have been identified that participate in reversible and irreversible attachment and biofilm maturation, there is a still a significant knowledge gap regarding the c-di-GMP output systems in this organism. Even for the well-characterized Pel system, where c-di-GMP-mediated transcriptional regulation is now well documented, how binding of c-di-GMP by PelD stimulates Pel production is not understood in any detail. Similarly, c-di-GMP-mediated control of swimming, swarming and twitching also remains to be elucidated. Thus, despite terrific advances in our understanding of P. aeruginosa biofilm formation and the role of c-di-GMP in this process since the last version of this book (indeed there was no chapter on c-di-GMP!) there is still much to learn. PMID:26104694

  10. c-di-GMP and its Effects on Biofilm Formation and Dispersion: a Pseudomonas Aeruginosa Review.

    PubMed

    Ha, Dae-Gon; O'Toole, George A

    2015-04-01

    Since its initial discovery as an allosteric factor regulating cellulose biosynthesis in Gluconacetobacter xylinus, the list of functional outputs regulated by c-di-GMP has grown. We have focused this article on one of these c-di-GMP-regulated processes, namely, biofilm formation in the organism Pseudomonas aeruginosa. The majority of diguanylate cyclases and phosphodiesterases encoded in the P. aeruginosa genome still remain uncharacterized; thus, there is still a great deal to be learned about the link between c-di-GMP and biofilm formation in this microbe. In particular, while a number of c-di-GMP metabolizing enzymes have been identified that participate in reversible and irreversible attachment and biofilm maturation, there is a still a significant knowledge gap regarding the c-di-GMP output systems in this organism. Even for the well-characterized Pel system, where c-di-GMP-mediated transcriptional regulation is now well documented, how binding of c-di-GMP by PelD stimulates Pel production is not understood in any detail. Similarly, c-di-GMP-mediated control of swimming, swarming and twitching also remains to be elucidated. Thus, despite terrific advances in our understanding of P. aeruginosa biofilm formation and the role of c-di-GMP in this process since the last version of this book (indeed there was no chapter on c-di-GMP!) there is still much to learn.

  11. Crystal structure of tris-(di-methyl-amido-κN)-bis-(di-methyl-amine-κN)-zirconium(IV) iodide.

    PubMed

    Clark, Wesley D; Akurathi, Gopalakrishna; Valle, Henry U; Hollis, T Keith

    2016-01-01

    Zirconium amides have become increasingly popular and useful due to their widespread use as precursors to other zirconium complexes and their use in the production of solid oxide fuel cells (SOFCs). Herein we report the mol-ecular structure of tris-(di-methyl-amido)-bis-(di-methyl-amine)-zirconium(IV) iodide, [Zr(C2H6N)3(C2H7N)2]I. The bond lengths and bond angles are consistent with a slightly distorted trigonal-bipyramidal coordination geometry around the metal atom. N⋯I contacts of 3.6153 (15) and 3.5922 (14) Å are consistent with the presence of N-H⋯I inter-actions. These N-H⋯I inter-actions link the complex cations and iodide anions into extended chains that propagate parallel to the a axis. PMID:26870590

  12. 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-di

  13. An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis

    PubMed Central

    Gundlach, Jan; Mehne, Felix M. P.; Herzberg, Christina; Kampf, Jan; Valerius, Oliver; Kaever, Volkhard

    2015-01-01

    ABSTRACT Gram-positive bacteria synthesize the second messenger cyclic di-AMP (c-di-AMP) to control cell wall and potassium homeostasis and to secure the integrity of their DNA. In the firmicutes, c-di-AMP is essential for growth. The model organism Bacillus subtilis encodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-AMP, respectively. Among the three cyclases, CdaA is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di-AMP that is required for cell wall homeostasis. Here, we demonstrate that CdaA localizes to the membrane and forms a complex with the regulatory protein CdaR and the glucosamine-6-phosphate mutase GlmM. Interestingly, cdaA, cdaR, and glmM form a gene cluster that is conserved throughout the firmicutes. This conserved arrangement and the observed interaction between the three proteins suggest a functional relationship. Our data suggest that GlmM and GlmS are involved in the control of c-di-AMP synthesis. These enzymes convert glutamine and fructose-6-phosphate to glutamate and glucosamine-1-phosphate. c-di-AMP synthesis is enhanced if the cells are grown in the presence of glutamate compared to that in glutamine-grown cells. Thus, the quality of the nitrogen source is an important signal for c-di-AMP production. In the analysis of c-di-AMP-degrading phosphodiesterases, we observed that both phosphodiesterases, GdpP and PgpH (previously known as YqfF), contribute to the degradation of the second messenger. Accumulation of c-di-AMP in a gdpP pgpH double mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA. IMPORTANCE Bacteria use second messengers for signal transduction. Cyclic di-AMP (c-di-AMP) is the only second messenger known so far that is essential for a large group of bacteria. We have studied the regulation of c-di-AMP synthesis and the role of the phosphodiesterases that degrade this second

  14. Cost-effective isobaric tagging for quantitative phosphoproteomics using DiART reagents.

    PubMed

    Ramsubramaniam, Nikhil; Tao, Feng; Li, Shuwei; Marten, Mark R

    2013-12-01

    We describe the use of an isobaric tagging reagent, Deuterium isobaric Amine Reactive Tag (DiART), for quantitative phosphoproteomic experiments. Using DiART tagged custom mixtures of two phosphorylated peptides from alpha casein and their non-phosphorylated counterparts, we demonstrate the compatibility of DiART with TiO2 affinity purification of phosphorylated peptides. Comparison of theoretical vs. experimental reporter ion ratios reveals accurate quantification of phosphorylated peptides over a dynamic range of more than 15-fold. Using DiART labelling and TiO2 enrichment (DiART-TiO2) with large quantities of proteins (8 mg) from the cell lysate of model fungus Aspergillus nidulans, we quantified 744 unique phosphopeptides. Overlap of median values of TiO2 enriched phosphopeptides with theoretical values indicates accurate trends. Altogether these findings confirm the feasibility of performing quantitative phosphoproteomic experiments in a cost-effective manner using isobaric tagging reagents, DiART.

  15. Three clinical cases of the DiGeorge syndrome manifested with the biliary system disease.

    PubMed

    Tabutsadze, T; Pachkoria, Kh; Atuashvili, G

    2007-11-01

    DiGeorge syndrome is a rare congenital disease that affects the baby's immune system. Its symptoms vary greatly between individuals but commonly include a history of recurrent infection, heart defects, and characteristic facial features. Few cases of DiGeorge syndrome have been reported in adults. The article describes rare (three cases of DiGeorge syndrome) in adults (18, 32 and 34 years old patients) in Georgia (Caucasus). In clinical practice DiGeorge syndrome may proceed under the course of gastroenterologic, endocrine, nervous and surgical symptoms. 3 cases of DiGeorge syndrome are reported in the article. The authors describe DiGeroge syndrome as a multidisciplinary disorder; it is masqueraded by acute surgical diseases; with sharp immunodeficiency and endocrine, cardiologic and neurologic semiotics.

  16. Mono-(3-carboxypropyl) phthalate, a metabolite of di-n-octyl phthalate.

    PubMed

    Calafat, Antonia M; Silva, Manori J; Reidy, John A; Earl Gray, L; Samandar, Ella; Preau, James L; Herbert, Arnetra R; Needham, Larry L

    2006-02-01

    Di-n-octyl phthalate (DnOP) is found as a component of mixed C6-C10 linear-chain phthalates used as plasticizers in various polyvinyl chloride applications, including flooring and carpet tiles. Following exposure and absorption, DnOP is metabolized to its hydrolytic monoester, mono-n-octyl phthalate (MnOP), and other oxidative products. The urinary levels of one of these oxidative metabolites, mono-(3-carboxypropyl) phthalate (MCPP), were about 560-fold higher than MnOP in Sprague-Dawley rats dosed with DnOP by gavage. Furthermore, MCPP was also found in the urine of rats dosed with di-isooctyl phthalate (DiOP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP), di-(2-ethylhexyl) phthalate, and di-n-butyl phthalate (DBP), although at concentrations considerably lower than in rats given similar concentrations of DnOP. The comparatively much higher urinary concentrations of MCPP than of the hydrolytic monoesters of the high-molecular-weight phthalates DiOP, DiNP, and DiDP in the exposed rats suggest that these monoesters may be poor biomarkers of exposure to their precursor phthalates and may explain the relatively low frequency of detection of these monoester metabolites in human populations. MCPP and MnOP were also measured in 267 human urine samples. The frequent detection and higher urinary concentrations of MCPP than MnOP suggest that exposure to DnOP might be higher than previously thought based on the measurements of MnOP alone. However, because MCPP is also a minor metabolite of DBP and other phthalates in rats, and the metabolism of phthalates in rodents and humans may differ, additional data on the absorption, distribution, metabolism, and elimination of MCPP are needed to completely understand the extent of human exposure to DnOP from the urinary concentrations of MCPP. PMID:16263692

  17. Cyclic Di-GMP Riboswitch-Regulated Type IV Pili Contribute to Aggregation of Clostridium difficile

    PubMed Central

    Bordeleau, Eric; Purcell, Erin B.; Lafontaine, Daniel A.; Fortier, Louis-Charles; Tamayo, Rita

    2014-01-01

    Clostridium difficile is an anaerobic Gram-positive bacterium that causes intestinal infections with symptoms ranging from mild diarrhea to fulminant colitis. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that typically regulates the switch from motile, free-living to sessile and multicellular behaviors in Gram-negative bacteria. Increased intracellular c-di-GMP concentration in C. difficile was recently shown to reduce flagellar motility and to increase cell aggregation. In this work, we investigated the role of the primary type IV pilus (T4P) locus in c-di-GMP-dependent cell aggregation. Inactivation of two T4P genes, pilA1 (CD3513) and pilB1 (CD3512), abolished pilus formation and significantly reduced cell aggregation under high c-di-GMP conditions. pilA1 is preceded by a putative c-di-GMP riboswitch, predicted to be transcriptionally active upon c-di-GMP binding. Consistent with our prediction, high intracellular c-di-GMP concentration increased transcript levels of T4P genes. In addition, single-round in vitro transcription assays confirmed that transcription downstream of the predicted transcription terminator was dose dependent and specific to c-di-GMP binding to the riboswitch aptamer. These results support a model in which T4P gene transcription is upregulated by c-di-GMP as a result of its binding to an upstream transcriptionally activating riboswitch, promoting cell aggregation in C. difficile. PMID:25512308

  18. Ring hydroxylation of di-t-butylhydroxytoluene by rat liver microsomal preparations

    PubMed Central

    Shaw, Yon-Shong; Chen, Chiadao

    1972-01-01

    3,5-Di-t-butylhydroxytoluene (compound I) was converted into 4-hydroperoxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (compound II), 4-hydroxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (compound III) and 2,6-di-t-butyl-4-hydroxymethylphenol (compound IV) by rat liver microsomal preparations in the presence of NADPH and air. The oxidation of compound (I) by m-chloroperbenzoic acid also produced the same compounds. These results suggest that hydroperoxide can be an intermediate in aromatic hydroxylation and that biological oxygenations resemble per-acid reactions. PMID:4404965

  19. Structural Basis of Ligand Binding by a C-di-GMP Riboswitch

    SciTech Connect

    Smith, K.; Lipchock, S; Ames, T; Wang, J; Breaker, R; Strobel, S

    2009-01-01

    The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structural data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.

  20. Cyclic di-GMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile.

    PubMed

    Bordeleau, Eric; Purcell, Erin B; Lafontaine, Daniel A; Fortier, Louis-Charles; Tamayo, Rita; Burrus, Vincent

    2015-03-01

    Clostridium difficile is an anaerobic Gram-positive bacterium that causes intestinal infections with symptoms ranging from mild diarrhea to fulminant colitis. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that typically regulates the switch from motile, free-living to sessile and multicellular behaviors in Gram-negative bacteria. Increased intracellular c-di-GMP concentration in C. difficile was recently shown to reduce flagellar motility and to increase cell aggregation. In this work, we investigated the role of the primary type IV pilus (T4P) locus in c-di-GMP-dependent cell aggregation. Inactivation of two T4P genes, pilA1 (CD3513) and pilB1 (CD3512), abolished pilus formation and significantly reduced cell aggregation under high c-di-GMP conditions. pilA1 is preceded by a putative c-di-GMP riboswitch, predicted to be transcriptionally active upon c-di-GMP binding. Consistent with our prediction, high intracellular c-di-GMP concentration increased transcript levels of T4P genes. In addition, single-round in vitro transcription assays confirmed that transcription downstream of the predicted transcription terminator was dose dependent and specific to c-di-GMP binding to the riboswitch aptamer. These results support a model in which T4P gene transcription is upregulated by c-di-GMP as a result of its binding to an upstream transcriptionally activating riboswitch, promoting cell aggregation in C. difficile.

  1. Stimulation of innate immunity by in vivo cyclic di-GMP synthesis using adenovirus.

    PubMed

    Koestler, Benjamin J; Seregin, Sergey S; Rastall, David P W; Aldhamen, Yasser A; Godbehere, Sarah; Amalfitano, Andrea; Waters, Christopher M

    2014-11-01

    The bacterial second messenger cyclic di-GMP (c-di-GMP) stimulates inflammation by initiating innate immune cell recruitment and triggering the release of proinflammatory cytokines and chemokines. These properties make c-di-GMP a promising candidate for use as a vaccine adjuvant, and numerous studies have demonstrated that administration of purified c-di-GMP with different antigens increases protection against infection in animal models. Here, we have developed a novel approach to produce c-di-GMP inside host cells as an adjuvant to exploit a host-pathogen interaction and initiate an innate immune response. We have demonstrated that c-di-GMP can be synthesized in vivo by transducing a diguanylate cyclase (DGC) gene into mammalian cells using an adenovirus serotype 5 (Ad5) vector. Expression of DGC led to the production of c-di-GMP in vitro and in vivo, and this was able to alter proinflammatory gene expression in murine tissues and increase the secretion of numerous cytokines and chemokines when administered to animals. Furthermore, coexpression of DGC modestly increased T-cell responses to a Clostridium difficile antigen expressed from an adenovirus vaccine, although no significant differences in antibody titers were observed. This adenovirus c-di-GMP delivery system offers a novel method to administer c-di-GMP as an adjuvant to stimulate innate immunity during vaccination.

  2. Structural basis of ligand binding by a c-di-GMP riboswitch.

    PubMed

    Smith, Kathryn D; Lipchock, Sarah V; Ames, Tyler D; Wang, Jimin; Breaker, Ronald R; Strobel, Scott A

    2009-12-01

    The second messenger signaling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 A resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structural data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling. PMID:19898477

  3. In vitro selection of allosteric ribozymes that sense the bacterial second messenger c-di-GMP.

    PubMed

    Furukawa, Kazuhiro; Gu, Hongzhou; Breaker, Ronald R

    2014-01-01

    Recently, a number of study have shown the ligand-dependent allosteric ribozymes can be harnessed as biosensors, high-throughput screening, and agents for the control of gene expression in vivo, called artificial riboswitches. In this chapter, we describe how in vitro selection can be used to create an allosteric ribozyme that senses bacterial second messenger cyclic-di-GMP (c-di-GMP). A hammerhead ribozyme was joined to a natural c-di-GMP class I riboswitch aptamer via communication modules. Both c-di-GMP-activating and -inhibiting ribozyme can be obtained by this approach. PMID:24549622

  4. The Dusty View of DI from ESO Chile

    NASA Astrophysics Data System (ADS)

    Boehnhardt, H.; Ageorges, N.; Bagnulo, S.; Barrera, L.; Bonev, T.; Hainaut, O.; Jehin, E.; Käufl, H. U.; Kerber, F.; Locurto, G.; Manfroid, J.; Marco, O.; Pantin, E.; Pompei, E.; Rauer, H.; Saviane, I.; Selman, F.; Sterken, C.; Tozzi, G. P.; Weiler, M.

    Around the time of the impact of NASA's Deep Impact (DI) mission at comet 9P/Tempel 1, in total 6 telescopes with altogether 7 different instruments, located at the La Silla (LSO) and Paranal (VLT) Observatories of the European Southern Observatory (ESO) in Chile, were used to characterize the dust properties before and after the event. The ejecta cloud expanded at an average speed of about 200 ms-1during the first hours after the event. It reached stagnation distance of 25000 km about 3 days after impact. The pre-impact dust jet and fan activity (`porcupine' pattern) remained undisturbed after impact. In our measurements the jet activity can be traced to a few 100 km nucleus distance. In total 9 comastructures are identified which may originate from at least 4 regions of enhanced dust emission on the nucleus - one of this region may in fact be multiple. No obvious signatures of a new active region created by DI are found. The overall dust production during the impact compares to about 5-10 h of normal activity. The global expansion geometry of the DI cloud is compatible with a majority of dust grains in the micron size range. Indications exist for asymmetric brightness and colour distributions of the dust in the ejecta cloud. The dust temperature rose from about 280-290 K before to 330 K one day after the event and fell to pre-impact level the day thereafter. The dust reflected sunlight was found to be linearly polarized at about 7.5% in the visible and near-IR, at constant level within about 4000 km from the nucleus. No circular polarization of the dust is detected.

  5. Balsacones D-I, dihydrocinnamoyl flavans from Populus balsamifera buds.

    PubMed

    Simard, François; Legault, Jean; Lavoie, Serge; Pichette, André

    2014-04-01

    A phytochemical investigation of an ethanolic extract from Populus balsamifera L. buds resulted in the isolation and characterization of twelve new flavan derivatives consisting of six pairs of enantiomers. Structures of (+) and (-)-balsacones D-I were elucidated based on spectroscopic data (1D and 2D NMR, MS) and their absolute configurations were established using X-ray single crystal diffraction analysis and ECD computational calculations. Antibacterial activity and cytotoxicity of all purified enantiomers were evaluated in vitro against Staphylococcus aureus and human skin fibroblast cells, respectively.

  6. Bis(benzyl­ammonium) di­hydrogen diphosphate

    PubMed Central

    Saad, Ahlem Ben; Elboulali, Adel; Ratel-Ramond, Nicolas; Mohamed, Rzaigui; Toumi, Samah Akriche

    2014-01-01

    The asymmetric unit of the title salt, 2C6H5CH2NH3 +·H2P2O7 2−, contains two independent benzyl­ammonium cations and a di­hydrogen diphosphate dianion. In the crystal, O—H⋯O and N—H⋯O hydrogen bonds link the cations and anions, forming a two-dimensional network parallel to (010). Within this network, weak C—H⋯O hydrogen bonds are observed. PMID:24526977

  7. The Hydrolysis of Di-Isopropyl Methylphosphonate in Ground Water

    SciTech Connect

    Sega, G.A., Tomkins, B.A., Griest, W.H., Bayne, C.K.

    1997-12-31

    Di-isopropyl methylphosphonate (DIMP) is a byproduct from the manufacture of the nerve agent Sarin. The persistence of DIMP in the ground water is an important question in evaluating the potential environmental impacts of DIMP contamination. The half-life of DIMP in ground water at 10 deg C was estimated to be 500 years with a 95% confidence interval of 447 to 559 years from measurements of the hydrolysis rates at temperatures between 70 to 98 deg C.Extrapolation of the kinetics to 10 deg C used the Arrhenius equation, and calculation of the half-life assumed first-order kinetics. Inorganic phosphate was not detected.

  8. Sonar investigations in the Laghi di Monticchio (Mt. Vúlture, Italy)

    NASA Astrophysics Data System (ADS)

    Hansen, Ralph B.

    Sonar profiles across the Lago Grande and Lago Piccolo di Monticchio (two lakes in southern Italy, 20 km S of Melfi) were recorded to get knowledge on the lake basins an their surface prior coring. The combination of echo-graph data with digital landscape modelling was suitable for the detection and interpretation of complex structures of the lake bottom. The interpretation of the model shows the distortion of an old continuous sedimentation by younger tectonic events. The presence of terraces above and below the present-day lake level are interpreted as response to paleoclimatic fluctuations and human activities.

  9. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    SciTech Connect

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  10. C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage

    SciTech Connect

    Tzeng, W.-P.; Frey, Teryl K. . E-mail: tfrey@gsu.edu

    2006-12-20

    Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5' end of the capsid protein (C) gene that has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, it was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5' end of the C gene and the 3' end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.

  11. Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

    PubMed Central

    Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

    2013-01-01

    ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

  12. Functional Analysis of a c-di-AMP-specific Phosphodiesterase MsPDE from Mycobacterium smegmatis

    PubMed Central

    Tang, Qing; Luo, Yunchao; Zheng, Cao; Yin, Kang; Ali, Maria Kanwal; Li, Xinfeng; He, Jin

    2015-01-01

    Cyclic di‑AMP (c-di-AMP) is a second signaling molecule involved in the regulation of bacterial physiological processes and interaction between pathogen and host. However, the regulatory network mediated by c-di-AMP in Mycobacterium remains obscure. In M. smegmatis, a diadenylate cyclase (DAC) was reported recently, but there is still no investigation on c-di-AMP phosphodiesterase (PDE). Here, we provide a systematic study on signaling mechanism of c-di-AMP PDE in M. smegmatis. Based on our enzymatic analysis, MsPDE (MSMEG_2630), which contained a DHH-DHHA1 domain, displayed a 200-fold higher hydrolytic efficiency (kcat/Km) to c-di-AMP than to c-di-GMP. MsPDE was capable of converting c-di-AMP to pApA and AMP, and hydrolyzing pApA to AMP. Site-directed mutations in DHH and DHHA1 revealed that DHH domain was critical for the phosphodiesterase activity. To explore the regulatory role of c-di-AMP in vivo, we constructed the mspde mutant (Δmspde) and found that deficiency of MsPDE significantly enhanced intracellular C12-C20 fatty acid accumulation. Deficiency of DAC in many bacteria results in cell death. However, we acquired the M. smegmatis strain with DAC gene disrupted (ΔmsdisA) by homologous recombination approach. Deletion of msdisA reduced bacterial C12-C20 fatty acids production but scarcely affected bacterial survival. We also provided evidences that superfluous c-di-AMP in M. smegmatis could lead to abnormal colonial morphology. Collectively, our results indicate that MsPDE is a functional c-di-AMP-specific phosphodiesterase both in vitro and in vivo. Our study also expands the regulatory network mediated by c-di-AMP in M. smegmatis. PMID:26078723

  13. The fate of di-(3,5-di-tert.-butyl-4-hydroxyphenyl)methane (Ionox 220) in the rat

    PubMed Central

    Wright, A. S.; Crowne, R. S.; Hathway, D. E.

    1966-01-01

    1. A large proportion of a single oral dose of [14C]Ionox 220 to rats is eliminated in 24 days: 89·3–97·4% of the label is excreted in the faeces (much of this is eliminated in the first 4 days after dosage), 1% in the urine and less than 0·1% in the expired gases; 4·06% of 14C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 2. About 87% of 14C in the faeces is due to unchanged antioxidant, 5% to the quinone methide, 5% to the free acid and 3% to an unidentified polar constituent. Three-fifths of 14C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid and the remainder to the ester glucuronide. In three individual animals, one-half of 14C in the bile is due to the free acid, one-quarter to the ester glucuronide and the remainder to unchanged antioxidant, whereas in another all of 14C in the bile is due to Ionox 220. About 97% of 14C in the body fat is due to unchanged antioxidant and the remainder to the free acid. 3. Up to 20% of a single oral dose of Ionox 220 is absorbed in rats: 13–14% is metabolized. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid accounts for just over 5% of a dose of Ionox 220, 3,5-di-tert.-butyl-4-hydroxybenzoyl-β-d-glucopyranosiduronic acid for less than 0·4%, the quinone methide for just over 5% and an unidentified compound for less than 3%. 4. The physiological and biochemical implications of ingesting Ionox 220 are discussed. PMID:5965331

  14. Critical cleaning agents for Di-2-ethylhexyl sebacate.

    SciTech Connect

    Hartley, Mya; Archuleta, Kim M.

    2013-08-01

    It is required that Di-2-ethylhexyl Sebacate oil, also commonly known as Dioctyl Sebacate oil, be thoroughly removed from certain metals, in this case stainless steel parts with narrow, enclosed spaces. Dioctyl Sebacate oil is a synthetic oil with a low compressibility. As such, it is ideally used for high pressure calibrations. The current method to remove the Dioctyl Sebacate from stainless steel parts with narrow, enclosed spaces is a labor-intensive, multi-step process, including a detergent clean, a deionized (DI) water rinse, and several solvent rinses, to achieve a nonvolatile residue of 0.04 mg per 50 mL rinse effluent. This study was undertaken to determine a superior detergent/solvent cleaning method for the oil to reduce cleaning time and/or the amount of detergent/solvent used. It was determined that while some detergent clean the oil off the metal better than the current procedure, using only solvents obtained the best result. In addition, it can be inferred, based on elevated temperature test results, that raising the temperature of the oil-contaminated stainless steel parts to approximately 50ÀC will provide for improved cleaning efficacy.

  15. RATE CONSTANTS FOR THE REACTIONS OF OH RADICALS AND CL ATOMS WITH DI-N-PROPYL ETHER AND DI-N-BUTYL ETHER AND THEIR DEUTERATED ANALOGS. (R825252)

    EPA Science Inventory

    Using relative rate methods, rate constants for the gas-phase reactions of OH radicals and Cl atoms with di-n-propyl ether, di-n-propyl ether-d14, di-n-butyl ether and di-n-butyl ether-d18 have been measured at 296 ? 2 K and atmos...

  16. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SANITIZERS Antioxidants and Stabilizers § 178.2550 4-Hydroxymethyl-2,6-di-tert-butylphenol. 4-Hydroxymethyl-2,6-di-tert-butyl-phenol may be safely used as an antioxidant in articles intended for use in contact... solidification point of 140°-141 °C. (b) The concentration of the additive and any other permitted...

  17. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SANITIZERS Antioxidants and Stabilizers § 178.2550 4-Hydroxymethyl-2,6-di-tert-butylphenol. 4-Hydroxymethyl-2,6-di-tert-butyl-phenol may be safely used as an antioxidant in articles intended for use in contact... solidification point of 140°-141 °C. (b) The concentration of the additive and any other permitted...

  18. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SANITIZERS Antioxidants and Stabilizers § 178.2550 4-Hydroxymethyl-2,6-di-tert-butylphenol. 4-Hydroxymethyl-2,6-di-tert-butyl-phenol may be safely used as an antioxidant in articles intended for use in contact... solidification point of 140°-141 °C. (b) The concentration of the additive and any other permitted...

  19. New compatible solutes related to Di-myo-inositol-phosphate in members of the order Thermotogales.

    PubMed Central

    Martins, L O; Carreto, L S; Da Costa, M S; Santos, H

    1996-01-01

    The accumulation of intracellular organic solutes was examined in six species of the order Thermotogales by nuclear magnetic resonance spectroscopy. The newly discovered compounds di-2-O-beta-mannosyl-di-myo-inositol-1,1'(3,3')-phosphate and di-myo-inositol-1,3'-phosphate were identified in Thermotoga maritima and Thermotoga neapolitana. In the latter species, at the optimum temperature and salinity the organic solute pool was composed of di-myo-inositol-1,1'(3,3')-phosphate, beta-glutamate, and alpha-glutamate in addition to di-myo-inositol-1,3'-phosphate and di-2-O-beta-mannosyl-di-myo-inositol-1,1'(3,3')-phosphate. The concentrations of the last two solutes increased dramatically at supraoptimal growth temperatures, whereas beta-glutamate increased mainly in response to a salinity stress. Nevertheless, di-myo-inositol-1,1'(3,3')-phosphate was the major compatible solute at salinities above the optimum for growth. The amino acids alpha-glutamate and proline were identified under optimum growth conditions in Thermosipho africanus, and beta-mannosylglycerate, trehalose, and glycine betaine were detected in Petrotoga miotherma. Organic solutes were not detected, under optimum growth conditions, in Thermotoga thermarum and Fervidobacterium islandicum, which have a low salt requirement or none. PMID:8824608

  20. Trigger phosphodiesterases as a novel class of c-di-GMP effector proteins

    PubMed Central

    2016-01-01

    The bacterial second messenger c-di-GMP controls bacterial biofilm formation, motility, cell cycle progression, development and virulence. It is synthesized by diguanylate cyclases (with GGDEF domains), degraded by specific phosphodiesterases (PDEs, with EAL of HD-GYP domains) and sensed by a wide variety of c-di-GMP-binding effectors that control diverse targets. c-di-GMP-binding effectors can be riboswitches as well as proteins with highly diverse structures and functions. The latter include ‘degenerate’ GGDEF/EAL domain proteins that are enzymatically inactive but still able to bind c-di-GMP. Surprisingly, two enzymatically active ‘trigger PDEs’, the Escherichia coli proteins PdeR and PdeL, have recently been added to this list of c-di-GMP-sensing effectors. Mechanistically, trigger PDEs are multifunctional. They directly and specifically interact with a macromolecular target (e.g. with a transcription factor or directly with a promoter region), whose activity they control by their binding and degradation of c-di-GMP—their PDE activity thus represents the c-di-GMP sensor or effector function. In this process, c-di-GMP serves as a regulatory ligand, but in contrast to classical allosteric control, this ligand is also degraded. The resulting kinetics and circuitry of control are ideally suited for trigger PDEs to serve as key components in regulatory switches. This article is part of the themed issue ‘The new bacteriology’. PMID:27672149

  1. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SANITIZERS Antioxidants and Stabilizers § 178.2550 4-Hydroxymethyl-2,6-di-tert-butylphenol. 4-Hydroxymethyl-2,6-di-tert-butyl-phenol may be safely used as an antioxidant in articles intended for use in contact... solidification point of 140°-141 °C. (b) The concentration of the additive and any other permitted...

  2. Trigger phosphodiesterases as a novel class of c-di-GMP effector proteins.

    PubMed

    Hengge, Regine

    2016-11-01

    The bacterial second messenger c-di-GMP controls bacterial biofilm formation, motility, cell cycle progression, development and virulence. It is synthesized by diguanylate cyclases (with GGDEF domains), degraded by specific phosphodiesterases (PDEs, with EAL of HD-GYP domains) and sensed by a wide variety of c-di-GMP-binding effectors that control diverse targets. c-di-GMP-binding effectors can be riboswitches as well as proteins with highly diverse structures and functions. The latter include 'degenerate' GGDEF/EAL domain proteins that are enzymatically inactive but still able to bind c-di-GMP. Surprisingly, two enzymatically active 'trigger PDEs', the Escherichia coli proteins PdeR and PdeL, have recently been added to this list of c-di-GMP-sensing effectors. Mechanistically, trigger PDEs are multifunctional. They directly and specifically interact with a macromolecular target (e.g. with a transcription factor or directly with a promoter region), whose activity they control by their binding and degradation of c-di-GMP-their PDE activity thus represents the c-di-GMP sensor or effector function. In this process, c-di-GMP serves as a regulatory ligand, but in contrast to classical allosteric control, this ligand is also degraded. The resulting kinetics and circuitry of control are ideally suited for trigger PDEs to serve as key components in regulatory switches.This article is part of the themed issue 'The new bacteriology'. PMID:27672149

  3. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi.

    PubMed

    Novak, Elizabeth A; Sultan, Syed Z; Motaleb, Md A

    2014-01-01

    In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

  4. c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.

    PubMed

    Song, Yu; Luciani, Marie-Françoise; Giusti, Corinne; Golstein, Pierre

    2015-02-15

    Cell death in the model organism Dictyostelium, as studied in monolayers in vitro, can be induced by the polyketide DIF-1 or by the cyclical dinucleotide c-di-GMP. c-di-GMP, a universal bacterial second messenger, can trigger innate immunity in bacterially infected animal cells and is involved in developmental cell death in Dictyostelium. We show here that c-di-GMP was not sufficient to induce cell death in Dictyostelium cell monolayers. Unexpectedly, it also required the DIF-1 polyketide. The latter could be exogenous, as revealed by a telling synergy between c-di-GMP and DIF-1. The required DIF-1 polyketide could also be endogenous, as shown by the inability of c-di-GMP to induce cell death in Dictyostelium HMX44A cells and DH1 cells upon pharmacological or genetic inhibition of DIF-1 biosynthesis. In these cases, c-di-GMP-induced cell death was rescued by complementation with exogenous DIF-1. Taken together, these results demonstrated that c-di-GMP could trigger cell death in Dictyostelium only in the presence of the DIF-1 polyketide or its metabolites. This identified another element of control to this cell death and perhaps also to c-di-GMP effects in other situations and organisms.

  5. Trigger phosphodiesterases as a novel class of c-di-GMP effector proteins.

    PubMed

    Hengge, Regine

    2016-11-01

    The bacterial second messenger c-di-GMP controls bacterial biofilm formation, motility, cell cycle progression, development and virulence. It is synthesized by diguanylate cyclases (with GGDEF domains), degraded by specific phosphodiesterases (PDEs, with EAL of HD-GYP domains) and sensed by a wide variety of c-di-GMP-binding effectors that control diverse targets. c-di-GMP-binding effectors can be riboswitches as well as proteins with highly diverse structures and functions. The latter include 'degenerate' GGDEF/EAL domain proteins that are enzymatically inactive but still able to bind c-di-GMP. Surprisingly, two enzymatically active 'trigger PDEs', the Escherichia coli proteins PdeR and PdeL, have recently been added to this list of c-di-GMP-sensing effectors. Mechanistically, trigger PDEs are multifunctional. They directly and specifically interact with a macromolecular target (e.g. with a transcription factor or directly with a promoter region), whose activity they control by their binding and degradation of c-di-GMP-their PDE activity thus represents the c-di-GMP sensor or effector function. In this process, c-di-GMP serves as a regulatory ligand, but in contrast to classical allosteric control, this ligand is also degraded. The resulting kinetics and circuitry of control are ideally suited for trigger PDEs to serve as key components in regulatory switches.This article is part of the themed issue 'The new bacteriology'.

  6. 40 CFR 721.9675 - Titanate [Ti6O13 (2-)], di-po-tas-sium.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Titanate , di-po-tas-sium. 721.9675 Section 721.9675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... Substances § 721.9675 Titanate , di-po-tas-sium. (a) Chemical substance and significant new uses subject...

  7. 40 CFR 721.9675 - Titanate [Ti6O13 (2-)], di-po-tas-sium.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Titanate , di-po-tas-sium. 721.9675 Section 721.9675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... Substances § 721.9675 Titanate , di-po-tas-sium. (a) Chemical substance and significant new uses subject...

  8. Secreted Cyclic Di-GMP Induces Stalk Cell Differentiation in the Eukaryote Dictyostelium discoideum

    PubMed Central

    Chen, Zhi-hui

    2015-01-01

    Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. In this review, we summarize the currently known mechanisms that control the major life cycle transitions of Dictyostelium and focus particularly on the role of c-di-GMP in stalk formation. Stalk cell differentiation has characteristics of autophagic cell death, a process that also occurs in higher eukaryotes. We discuss the respective roles of c-di-GMP and of another signal molecule, differentiation-inducing factor 1, in autophagic cell death in vitro and in stalk formation in vivo. PMID:26013485

  9. 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

    ABSTRACT Over the course of the last 3 decades the role of the second messenger cyclic di-GMP (c-di-GMP) as a master regulator of bacterial physiology was determined. Although the control over c-di-GMP levels via synthesis and breakdown and the allosteric regulation of c-di-GMP over receptor proteins (effectors) and riboswitches have been extensively studied, relatively few effectors have been identified and most are of unknown functions. The obligate predatory bacterium Bdellovibrio bacteriovorus has a peculiar dimorphic life cycle, in which a phenotypic transition from a free-living attack phase (AP) to a sessile, intracellular predatory growth phase (GP) is tightly regulated by specific c-di-GMP diguanylate cyclases. B. bacteriovorus also bears one of the largest complement of defined effectors, almost none of known functions, suggesting that additional proteins may be involved in c-di-GMP signaling. In order to uncover novel c-di-GMP effectors, a c-di-GMP capture-compound mass-spectroscopy experiment was performed on wild-type AP and host-independent (HI) mutant cultures, the latter serving as a proxy for wild-type GP cells. Eighty-four proteins were identified as candidate c-di-GMP binders. Of these proteins, 65 did not include any recognized c-di-GMP binding site, and 3 carried known unorthodox binding sites. Putative functions could be assigned to 59 proteins. These proteins are included in metabolic pathways, regulatory circuits, cell transport, and motility, thereby creating a potentially large c-di-GMP network. False candidate effectors may include members of protein complexes, as well as proteins binding nucleotides or other cofactors that were, respectively, carried over or unspecifically interacted with the capture compound during the pulldown. Of the 84 candidates, 62 were found to specifically bind the c-di-GMP capture compound in AP or in HI cultures, suggesting c-di-GMP control over the whole-cell cycle of the bacterium. High affinity and

  10. Secreted Cyclic Di-GMP Induces Stalk Cell Differentiation in the Eukaryote Dictyostelium discoideum.

    PubMed

    Chen, Zhi-hui; Schaap, Pauline

    2016-01-01

    Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. In this review, we summarize the currently known mechanisms that control the major life cycle transitions of Dictyostelium and focus particularly on the role of c-di-GMP in stalk formation. Stalk cell differentiation has characteristics of autophagic cell death, a process that also occurs in higher eukaryotes. We discuss the respective roles of c-di-GMP and of another signal molecule, differentiation-inducing factor 1, in autophagic cell death in vitro and in stalk formation in vivo. PMID:26013485

  11. DiSCuS: an open platform for (not only) virtual screening results management.

    PubMed

    Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Paweł

    2014-01-27

    DiSCuS, a "Database System for Compound Selection", has been developed. The primary goal of DiSCuS is to aid researchers in the steps subsequent to generating high-throughput virtual screening (HTVS) results, such as selection of compounds for further study, purchase, or synthesis. To do so, DiSCuS provides (1) a storage facility for ligand-receptor complexes (generated with external programs), (2) a number of tools for validating these complexes, such as scoring functions, potential energy contributions, and med-chem features with ligand similarity estimates, and (3) powerful searching and filtering options with logical operators. DiSCuS supports multiple receptor targets for a single ligand, so it can be used either to evaluate different variants of an active site or for selectivity studies. DiSCuS documentation, installation instructions, and source code can be found at http://discus.ibb.waw.pl .

  12. Secreted Cyclic Di-GMP Induces Stalk Cell Differentiation in the Eukaryote Dictyostelium discoideum.

    PubMed

    Chen, Zhi-hui; Schaap, Pauline

    2016-01-01

    Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. In this review, we summarize the currently known mechanisms that control the major life cycle transitions of Dictyostelium and focus particularly on the role of c-di-GMP in stalk formation. Stalk cell differentiation has characteristics of autophagic cell death, a process that also occurs in higher eukaryotes. We discuss the respective roles of c-di-GMP and of another signal molecule, differentiation-inducing factor 1, in autophagic cell death in vitro and in stalk formation in vivo.

  13. Chronic toxicity of di-n-butyl and di-n-octyl phthalate to Daphnia magna and the fathead minnow

    SciTech Connect

    McCarthy, J.F.; Whitmore, D.K.

    1985-01-01

    The toxicities of di-n-butyl phthalate (DBP) and di-n-octyl phthalate (DOP) were assessed by measuring the effect of exposure to these compounds on the fecundity of Daphnia magna and on the hatching and survival of the early life stages of the fathead minnow Pimephales promelas. For D. magna, exposure to 1.8 mg/L DBP or 1.0 mg/L DOP caused a significant reduction in reproduction. Doses of 0.56 mg/L DBP or 0.32 mg/L DOP had no significant effect in decreasing reproduction. Survival of fathead minnow embryos was decreased by exposure to 1.8 mg/L DBP; none of the embryos exposed to this dose hatched successfully. Hatching and larval survival were affected by exposure to 1.0 mg/L DBP, but not to 0.56 mg/L. Exposure to DOP did not affect survival of either early embryos or larvae of the fathead minnow at doses up to 10 mg/L (the highest dose tested). Hatching of the embryos was significantly decreased at 10 mg/L, but not at 3.2 mg/L DOP. 26 references, 4 figures, 11 tables.

  14. Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate.

    PubMed

    Jarfelt, Kirsten; Dalgaard, Majken; Hass, Ulla; Borch, Julie; Jacobsen, Helene; Ladefoged, Ole

    2005-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a well-known testicular toxicant inducing adverse effects in androgen responsive tissues. Therefore, di(2-ethylhexyl) adipate (DEHA) is currently being evaluated as a potential substitute for DEHP. Similarities in structure and metabolism of DEHP and DEHA have led to the hypothesis that DEHA can modulate the effects of DEHP. Wistar rats were gavaged with either vehicle, DEHP (300 or 750mg/kg bw/day) or DEHP (750mg/kg bw/day) in combination with DEHA (400mg/kg bw/day) from gestation day (GD) 7 to postnatal day (PND) 17. Decreased anogenital distance (AGD) and retention of nipples in male offspring were found in all three exposed groups. Dosed males exhibited decreased weights of ventral prostate and m. levator ani/bulbocavernosus. Histopathological investigations revealed alterations in testis morphology in both juvenile and adult animals. The litter size was decreased and postnatal mortality was increased in the combination group only, which is likely a combined effect of DEHP and DEHA. However, no combination effect was seen with respect to antiandrogenic effects, as males receiving DEHP in combination with DEHA did not exhibit more pronounced effects in the reproductive system than males receiving DEHP alone. PMID:15749265

  15. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    PubMed

    An, Shi-qi; Caly, Delphine L; McCarthy, Yvonne; Murdoch, Sarah L; Ward, Joseph; Febrer, Melanie; Dow, J Maxwell; Ryan, Robert P

    2014-10-01

    Bis-(3',5') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d)∼2 µM). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  16. Enhanced healing of full-thickness burn wounds using di-rhamnolipid

    PubMed Central

    Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

    2006-01-01

    The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213

  17. Responses to Elevated c-di-GMP Levels in Mutualistic and Pathogenic Plant-Interacting Bacteria

    PubMed Central

    Pérez-Mendoza, Daniel; Aragón, Isabel M.; Prada-Ramírez, Harold A.; Romero-Jiménez, Lorena; Ramos, Cayo; Gallegos, María-Trinidad; Sanjuán, Juan

    2014-01-01

    Despite a recent burst of research, knowledge on c-di-GMP signaling pathways remains largely fragmentary and molecular mechanisms of regulation and even c-di-GMP targets are yet unknown for most bacteria. Besides genomics or bioinformatics, accompanying alternative approaches are necessary to reveal c-di-GMP regulation in bacteria with complex lifestyles. We have approached this study by artificially altering the c-di-GMP economy of diverse pathogenic and mutualistic plant-interacting bacteria and examining the effects on the interaction with their respective host plants. Phytopathogenic Pseudomonas and symbiotic Rhizobium strains with enhanced levels of intracellular c-di-GMP displayed common free-living responses: reduction of motility, increased production of extracellular polysaccharides and enhanced biofilm formation. Regarding the interaction with the host plants, P. savastanoi pv. savastanoi cells containing high c-di-GMP levels formed larger knots on olive plants which, however, displayed reduced necrosis. In contrast, development of disease symptoms in P. syringae-tomato or P. syringae-bean interactions did not seem significantly affected by high c-di-GMP. On the other hand, increasing c-di-GMP levels in symbiotic R. etli and R. leguminosarum strains favoured the early stages of the interaction since enhanced adhesion to plant roots, but decreased symbiotic efficiency as plant growth and nitrogen contents were reduced. Our results remark the importance of c-di-GMP economy for plant-interacting bacteria and show the usefulness of our approach to reveal particular stages during plant-bacteria associations which are sensitive to changes in c-di-GMP levels. PMID:24626229

  18. Near-infrared Light Responsive Synthetic c-di-GMP Module for Optogenetic Applications

    PubMed Central

    2015-01-01

    Enormous potential of cell-based therapeutics is hindered by the lack of effective means to control genetically engineered cells in mammalian tissues. Here, we describe a synthetic module for remote photocontrol of engineered cells that can be adapted for such applications. The module involves photoactivated synthesis of cyclic dimeric GMP (c-di-GMP), a stable small molecule that is not produced by higher eukaryotes and therefore is suitable for orthogonal regulation. The key component of the photocontrol module is an engineered bacteriophytochrome diguanylate cyclase, which synthesizes c-di-GMP from GTP in a light-dependent manner. Bacteriophytochromes are particularly attractive photoreceptors because they respond to light in the near-infrared window of the spectrum, where absorption by mammalian tissues is minimal, and also because their chromophore, biliverdin IXα, is naturally available in mammalian cells. The second component of the photocontrol module, a c-di-GMP phosphodiesterase, maintains near-zero background levels of c-di-GMP in the absence of light, which enhances the photodynamic range of c-di-GMP concentrations. In the E. coli model used in this study, the intracellular c-di-GMP levels could be upregulated by light by >50-fold. Various c-di-GMP-responsive proteins and riboswitches identified in bacteria can be linked downstream of the c-di-GMP-mediated photocontrol module for orthogonal regulation of biological activities in mammals as well as in other organisms lacking c-di-GMP signaling. Here, we linked the photocontrol module to a gene expression output via a c-di-GMP-responsive transcription factor and achieved a 40-fold photoactivation of gene expression. PMID:24926804

  19. Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

    PubMed Central

    Galperin, Michael Y.; Gomelsky, Mark

    2013-01-01

    SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger. PMID:23471616

  20. Near-infrared light responsive synthetic c-di-GMP module for optogenetic applications.

    PubMed

    Ryu, Min-Hyung; Gomelsky, Mark

    2014-11-21

    Enormous potential of cell-based therapeutics is hindered by the lack of effective means to control genetically engineered cells in mammalian tissues. Here, we describe a synthetic module for remote photocontrol of engineered cells that can be adapted for such applications. The module involves photoactivated synthesis of cyclic dimeric GMP (c-di-GMP), a stable small molecule that is not produced by higher eukaryotes and therefore is suitable for orthogonal regulation. The key component of the photocontrol module is an engineered bacteriophytochrome diguanylate cyclase, which synthesizes c-di-GMP from GTP in a light-dependent manner. Bacteriophytochromes are particularly attractive photoreceptors because they respond to light in the near-infrared window of the spectrum, where absorption by mammalian tissues is minimal, and also because their chromophore, biliverdin IXα, is naturally available in mammalian cells. The second component of the photocontrol module, a c-di-GMP phosphodiesterase, maintains near-zero background levels of c-di-GMP in the absence of light, which enhances the photodynamic range of c-di-GMP concentrations. In the E. coli model used in this study, the intracellular c-di-GMP levels could be upregulated by light by >50-fold. Various c-di-GMP-responsive proteins and riboswitches identified in bacteria can be linked downstream of the c-di-GMP-mediated photocontrol module for orthogonal regulation of biological activities in mammals as well as in other organisms lacking c-di-GMP signaling. Here, we linked the photocontrol module to a gene expression output via a c-di-GMP-responsive transcription factor and achieved a 40-fold photoactivation of gene expression.

  1. Responses to elevated c-di-GMP levels in mutualistic and pathogenic plant-interacting bacteria.

    PubMed

    Pérez-Mendoza, Daniel; Aragón, Isabel M; Prada-Ramírez, Harold A; Romero-Jiménez, Lorena; Ramos, Cayo; Gallegos, María-Trinidad; Sanjuán, Juan

    2014-01-01

    Despite a recent burst of research, knowledge on c-di-GMP signaling pathways remains largely fragmentary and molecular mechanisms of regulation and even c-di-GMP targets are yet unknown for most bacteria. Besides genomics or bioinformatics, accompanying alternative approaches are necessary to reveal c-di-GMP regulation in bacteria with complex lifestyles. We have approached this study by artificially altering the c-di-GMP economy of diverse pathogenic and mutualistic plant-interacting bacteria and examining the effects on the interaction with their respective host plants. Phytopathogenic Pseudomonas and symbiotic Rhizobium strains with enhanced levels of intracellular c-di-GMP displayed common free-living responses: reduction of motility, increased production of extracellular polysaccharides and enhanced biofilm formation. Regarding the interaction with the host plants, P. savastanoi pv. savastanoi cells containing high c-di-GMP levels formed larger knots on olive plants which, however, displayed reduced necrosis. In contrast, development of disease symptoms in P. syringae-tomato or P. syringae-bean interactions did not seem significantly affected by high c-di-GMP. On the other hand, increasing c-di-GMP levels in symbiotic R. etli and R. leguminosarum strains favoured the early stages of the interaction since enhanced adhesion to plant roots, but decreased symbiotic efficiency as plant growth and nitrogen contents were reduced. Our results remark the importance of c-di-GMP economy for plant-interacting bacteria and show the usefulness of our approach to reveal particular stages during plant-bacteria associations which are sensitive to changes in c-di-GMP levels. PMID:24626229

  2. Bioremediation of di(2-ethylhexyl)phthalate in contaminated soil

    SciTech Connect

    Yu, J.J.; Ward, O.P.

    1995-12-31

    An efficient process has been developed for bioremediation of di(2-ethylhexyl) phthalate (DEHP) using soil tilling. The process involves application of a proprietary nutrient formulation and bioaugmentation with a site-specific DEHP-degrading inoculum. Laboratory feasibility studies were conducted to evaluate different factors that affect the process. The effects of moisture content, inoculum, nutrient rate, and initial DEHP concentration on biodegradation were investigated. A novel supplementary system--treatment system 2--was shown to accelerate DEHP degradation and facilitate remediation of residual persistent contaminant DEHP, which may be tightly bound to soil. In pilot studies, DEHP-contaminated soils were remediated to below 100 mg/kg in 70 to 80 days. Use of treatment system 2 resulted in reduction of contaminants to less than 15 mg/kg.

  3. Aqueous infrared carboxylate absorbances: Aliphatic di-acids

    USGS Publications Warehouse

    Cabaniss, S.E.; Leenheer, J.A.; McVey, I.F.

    1998-01-01

    Aqueous attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra of 18 aliphatic di-carboxylic acids are reported as a function of pH. The spectra show isosbestic points and intensity changes which indicate that Beer's law is obeyed, and peak frequencies lie within previously reported ranges for aqueous carboxylates and pure carboxylic acids. Intensity sharing from the symmetric carboxylate stretch is evident in many cases, so that bands which are nominally due to alkyl groups show increased intensity at higher pH. The asymmetric stretch of the HA- species is linearly related to the microscopic acidity constant of the H2A species, with ??pK 2 intervening atoms). The results suggest that aqueous ATR-FTIR may be able to estimate 'intrinsic' pKa values of carboxylic acids, in addition to providing quantitative estimates of ionization. ?? 1998 Elsevier Science B.V. All rights reserved.

  4. Taming of 3,4-Di(nitramino)furazan.

    PubMed

    Tang, Yongxing; Zhang, Jiaheng; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2015-12-30

    Highly energetic 3,4-di(nitramino)furazan (1, DNAF) was synthesized and confirmed structurally by using single-crystal X-ray diffraction. Its highly sensitive nature can be attributed to the shortage of hydrogen-bonding interactions and an interactive nitro chain in the crystal structure. In order to stabilize this structure, a series of corresponding nitrogen-rich salts (3-10) has been prepared and fully characterized. Among these energetic materials, dihydrazinium 3,4-dinitraminofurazanate (5) exhibits a very promising detonation performance (νD = 9849 m s(-1); P = 40.9 GPa) and is one of the most powerful explosives to date. To ensure the practical applications of 5, rather than preparing the salts of 1 through acid-base reactions, an alternative route through the nitration of N-ethoxycarbonyl-protected 3,4-diaminofurazan and aqueous alkaline workup was developed. PMID:26669520

  5. Crystal structure of 4-sulfamoylanilinium di­hydrogen phosphate

    PubMed Central

    Muthuselvi, C.; Mala, N.; Srinivasan, N.; Pandiarajan, S.; Krishnakumar, R. V.

    2014-01-01

    In the crystal structure of the title mol­ecular salt, C6H9N2O2S+·H2PO4 −, the sulfomylalinium cations and the di­hydrogen phosphate anions form independent [100] chains through Ns—H⋯O (s = sulfamo­yl) and O—H⋯O hydrogen bonds, respectively. The chains are cross-linked by Na—H⋯O (a = amine) hydrogen bonds, generating (010) sheets. Two C—H⋯O hydrogen bonds involving diametrically opposite C atoms in the benzene ring of the cation as donors form chains parallel to [202] in which P=O and P—OH groups are acceptors. Together, these inter­actions lead to a three-dimensional network. PMID:25309301

  6. The di-photon excess in a perturbative SUSY model

    NASA Astrophysics Data System (ADS)

    Benakli, Karim; Darmé, Luc; Goodsell, Mark D.; Harz, Julia

    2016-10-01

    We show that a 750 GeV di-photon excess as reported by the ATLAS and CMS experiments can be reproduced by the Minimal Dirac Gaugino Supersymmetric Standard Model (MDGSSM) without the need of any ad-hoc addition of new states. The scalar resonance is identified with the spin-0 partner of the Dirac bino. We perform a thorough analysis of constraints coming from the mixing of the scalar with the Higgs boson, the stability of the vacuum and the requirement of perturbativity of the couplings up to very high energy scales. We exhibit examples of regions of the parameter space that respect all the constraints while reproducing the excess. We point out how trilinear couplings that are expected to arise in supersymmetry-breaking mediation scenarios, but were ignored in the previous literature on the subject, play an important role.

  7. Cytotoxic Activity and Apoptosis-Inducing Potential of Di-spiropyrrolidino and Di-spiropyrrolizidino Oxindole Andrographolide Derivatives

    PubMed Central

    Hazra, Abhijit; Naskar, Subhendu; Nandy, Abhishek; Munda, Rudra Narayan; Das, Subhadip; Chatterjee, Nabanita; Mondal, Nirup Bikash; Banerjee, Sukdeb; Saha, Krishna Das

    2013-01-01

    Anticancer role of andrographolide is well documented. To find novel potent derivatives with improved cytotoxicity than andrographolide on cancer cells, two series of di-spiropyrrolidino- and di-spiropyrrolizidino oxindole andrographolide derivatives prepared by cyclo-addition of azomethine ylide along with sarcosine or proline (viz. sarcosine and proline series respectively) and substitution of different functional groups (-CH3, -OCH3 and halogens) were examined for their cytotoxic effect on a panel of six human cancer cell lines (colorectal carcinoma HCT116 cells, pancreatic carcinoma MiaPaCa-2 cells, hepatocarcinoma HepG2 cells, cervical carcinoma HeLa cells, lung carcinoma A549 and melanoma A375 cells). Except halogen substituted derivatives of proline series (viz. CY2, CY14 and CY15 for Br, Cl and I substitution respectively), none of the other derivatives showed improved cytotoxicity than andrographolide in the cancer cell lines examined. Order of cytotoxicity of the potent compounds is CY2>CY14>CY15>andrographolide. Higher toxicity was observed in HCT116, MiaPaCa-2 and HepG2 cells. CY2, induced death of HCT116 (GI50 10.5), MiaPaCa-2 (GI50 11.2) and HepG2 (GI50 16.6) cells were associated with cell rounding, nuclear fragmentation and increased percentage of apoptotic cells, cell cycle arrest at G1 phase, ROS generation, and involvement of mitochondrial pathway. Upregulation of Bax, Bad, p53, caspases-3,-9 and cleaved PARP; downregulation of Bcl-2, cytosolic NF-κB p65, PI3K and p-Akt; translocation of P53/P21, NF-κB p65 were seen in CY2 treated HCT116 cells. Thus, three halogenated di-spiropyrrolizidino oxindole derivatives of andrographolide are found to be more cytotoxic than andrographolide in some cancer cells. The most potent derivative, CY2 induced death of the cancer cells involves ROS dependent mitochondrial pathway like andrographolide. PMID:23472133

  8. Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice

    PubMed Central

    Gunjal, Ankush; Walunj, Manisha; Aghera, Hetal; Nariya, Mukesh; Goyal, Mandip R.

    2016-01-01

    Background: Triphalādi kvātha is well known herbal Ayurvedic formulation used in Prameha (~type 2 diabetes mellitus). In the present study, kvātha was converted into granules and assessed for its hypoglycemic and anti-hyperglycemic effects in albino mice. Materials and Methods: Triphalādi granules (650 mg/kg, p.o.) were administered in normal albino mice for assessment of hypoglycemic activity. Anti-hyperglycemic activity of Triphalādi granules was assessed in glucose (5 g/kg, p.o.) solution overloaded mice. The blood sugar level (BSL) was measured with the help of one touch easy glucometer. Results: Triphalādi granules produced significant decrease in blood glucose level after one hour in comparison to initial values while decreasing BSL by 27.92% in comparison to control group in normal albino mice. In hyperglycemic study, Triphalādi granules produced significant decrease the BSL after 2 hr. of administration compared to control group. Conclusion: Triphalādi granules have significant hypoglycemic and anti-hyperglycemic activity in mice with minimal effect on BSL below normal range. The studies suggest the potential role of Triphalādi granules as an alternative adjuvant therapy in diabetic individuals for the control of the blood glucose level. PMID:27621517

  9. Crystal structure of a c-di-AMP riboswitch reveals an internally pseudo-dimeric RNA.

    PubMed

    Jones, Christopher P; Ferré-D'Amaré, Adrian R

    2014-11-18

    Cyclic diadenosine monophosphate (c-di-AMP) is a second messenger that is essential for growth and homeostasis in bacteria. A recently discovered c-di-AMP-responsive riboswitch controls the expression of genes in a variety of bacteria, including important pathogens. To elucidate the molecular basis for specific binding of c-di-AMP by a gene-regulatory mRNA domain, we have determined the co-crystal structure of this riboswitch. Unexpectedly, the structure reveals an internally pseudo-symmetric RNA in which two similar three-helix-junction elements associate head-to-tail, creating a trough that cradles two c-di-AMP molecules making quasi-equivalent contacts with the riboswitch. The riboswitch selectively binds c-di-AMP and discriminates exquisitely against other cyclic dinucleotides, such as c-di-GMP and cyclic-AMP-GMP, via interactions with both the backbone and bases of its cognate second messenger. Small-angle X-ray scattering experiments indicate that global folding of the riboswitch is induced by the two bound cyclic dinucleotides, which bridge the two symmetric three-helix domains. This structural reorganization likely couples c-di-AMP binding to gene expression. PMID:25271255

  10. New insights into Legionella pneumophila biofilm regulation by c-di-GMP signaling.

    PubMed

    Pécastaings, Sophie; Allombert, Julie; Lajoie, Barbora; Doublet, Patricia; Roques, Christine; Vianney, Anne

    2016-09-01

    The waterborne pathogen Legionella pneumophila grows as a biofilm, freely or inside amoebae. Cyclic-di-GMP (c-di-GMP), a bacterial second messenger frequently implicated in biofilm formation, is synthesized and degraded by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), respectively. To characterize the c-di-GMP-metabolizing enzymes involved in L. pneumophila biofilm regulation, the consequences on biofilm formation and the c-di-GMP concentration of each corresponding gene inactivation were assessed in the Lens strain. The results showed that one DGC and two PDEs enhance different aspects of biofilm formation, while two proteins with dual activity (DGC/PDE) inhibit biofilm growth. Surprisingly, only two mutants exhibited a change in global c-di-GMP concentration. This study highlights that specific c-di-GMP pathways control L. pneumophila biofilm formation, most likely via temporary and/or local modulation of c-di-GMP concentration. Furthermore, Lpl1054 DGC is required to enable the formation a dense biofilm in response to nitric oxide, a signal for biofilm dispersion in many other species. PMID:27494738

  11. New insights into Legionella pneumophila biofilm regulation by c-di-GMP signaling.

    PubMed

    Pécastaings, Sophie; Allombert, Julie; Lajoie, Barbora; Doublet, Patricia; Roques, Christine; Vianney, Anne

    2016-09-01

    The waterborne pathogen Legionella pneumophila grows as a biofilm, freely or inside amoebae. Cyclic-di-GMP (c-di-GMP), a bacterial second messenger frequently implicated in biofilm formation, is synthesized and degraded by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), respectively. To characterize the c-di-GMP-metabolizing enzymes involved in L. pneumophila biofilm regulation, the consequences on biofilm formation and the c-di-GMP concentration of each corresponding gene inactivation were assessed in the Lens strain. The results showed that one DGC and two PDEs enhance different aspects of biofilm formation, while two proteins with dual activity (DGC/PDE) inhibit biofilm growth. Surprisingly, only two mutants exhibited a change in global c-di-GMP concentration. This study highlights that specific c-di-GMP pathways control L. pneumophila biofilm formation, most likely via temporary and/or local modulation of c-di-GMP concentration. Furthermore, Lpl1054 DGC is required to enable the formation a dense biofilm in response to nitric oxide, a signal for biofilm dispersion in many other species.

  12. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    SciTech Connect

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  13. Di-sulfated Keratan Sulfate as a Novel Biomarker for Mucopolysaccharidosis II, IVA, and IVB.

    PubMed

    Shimada, Tsutomu; Tomatsu, Shunji; Mason, Robert W; Yasuda, Eriko; Mackenzie, William G; Hossain, Jobayer; Shibata, Yuniko; Montaño, Adriana M; Kubaski, Francyne; Giugliani, Roberto; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E; Fukao, Toshiyuki; Orii, Tadao

    2015-01-01

    Keratan sulfate (KS) is a storage material in mucopolysaccharidosis IV (MPS IV). However, no detailed analysis has been reported on subclasses of KS: mono-sulfated KS and di-sulfated KS. We established a novel method to distinguish and quantify mono- and di-sulfated KS using liquid chromatography-tandem mass spectrometry and measured both KS levels in various specimens.Di-sulfated KS was dominant in shark cartilage and rat serum, while mono-sulfated KS was dominant in bovine cornea and human serum. Levels of both mono- and di-sulfated KS varied with age in the blood and urine from control subjects and patients with MPS II and IVA. The mean levels of both forms of KS in the plasma/serum from patients with MPS II, IVA, and IVB were elevated compared with that in age-matched controls. Di-sulfated KS provided more significant difference between MPS IVA and the age-matched controls than mono-sulfated KS. The ratio of di-sulfated KS to total KS in plasma/serum increased with age in control subjects and patients with MPS II but was age independent in MPS IVA patients. Consequently, this ratio can discriminate younger MPS IVA patients from controls. Levels of mono- and di-sulfated KS in urine of MPS IVA and IVB patients were all higher than age-matched controls for all ages studied.In conclusion, the level of di-sulfated KS and its ratio to total KS can distinguish control subjects from patients with MPS II, IVA, and IVB, indicating that di-sulfated KS may be a novel biomarker for these disorders.

  14. Association of exposure to di-2-ethylhexylphthalate replacements with increased blood pressure in children and adolescents.

    PubMed

    Trasande, Leonardo; Attina, Teresa M

    2015-08-01

    Phthalates are environmental chemicals widely used in consumer and personal care products. In this study, we examined associations of urinary phthalates with blood pressure, triglycerides, and lipoproteins in children and adolescents, performing a cross-sectional analysis of a subsample of US children 6 to 19 years of age who participated in the National Health and Nutrition Examination Survey between the years 2009 and 2012. We quantified exposure to common environmental phthalates, with a focus on the dietary contaminant di-2-ethylhexylphthalate and 2 increasingly used replacements, di-isononyl phthalate and di-isodecyl phthalate, based on micromolar concentration of urinary metabolites. We assessed descriptive, univariate, and multivariable associations with blood pressure and lipids. Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass, metabolites of di-2-ethylhexylphthalate, di-isononyl phthalate, and di-isodecyl phthalate were associated with higher age-, sex- and height-standardized blood pressure. For each log unit increase in di-isodecyl phthalate metabolites, a 0.105 standard deviation unit increase in systolic blood pressure z score was identified (P=0.004); for di-isononyl phthalate metabolites, a 0.113 standard deviation unit increment was identified (P=0.008). For di-2-ethylhexylphthalate metabolites, a 0.103 standard deviation unit increment (P=0.013) was detected. Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products showed an association with blood pressure (≥90th percentile) in univariate analysis, but this was no longer significant in our full multivariable model, suggesting specificity. Phthalate metabolites were not associated with triglycerides or high-density lipoproteins. Further, longitudinal studies are needed to confirm these associations and to assess opportunities for intervention. PMID:26156503

  15. Di-aqua-bis-(pyridine-2-carboxyl-ato-κ(2) N,O)zinc di-methyl-formamide hemisolvate.

    PubMed

    Croitor, Lilia; Chisca, Diana; Coropceanu, Eduard B; Fonari, Marina S

    2013-01-01

    In the title compound, [Zn(C6H4NO2)2(H2O)2]·0.5C3H7NO, the Zn(II) ion is coordinated in a distorted octa-hedral N2O4 environment by two N,O-chelating pyridine-2-carboxyl-ate ligands and two cis water mol-ecules. The chelating pyridine-2-carboxyl-ate ligands create two five-membered Zn/N/C/C/O rings, which form a dihedral angle of 86.4 (2)°. In the crystal, O-H⋯O hydrogen bonds link the complex mol-ecules into a two-dimensional network parallel to (100). The di-methyl-formamide solvent mol-ecule is disordered about a twofold rotation axis. PMID:24109277

  16. Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas.

    PubMed

    Cirillo, Teresa; Latini, Giuseppe; Castaldi, Maria Antonietta; Dipaola, Lucia; Fasano, Evelina; Esposito, Francesco; Scognamiglio, Gelsomina; Francesco, Fabio Di; Cobellis, Luigi

    2015-04-01

    Phthalates and bisphenol A (BPA) are ubiquitous contaminants identified as endocrine disruptors. Phthalates are worldwide used as plasticizers, in particular to improve the mechanical properties of polymers such as polyvinyl chloride. Because they are not chemically bound to the polymer, they tend to leach out with time and use. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) are the two most common phthalates. BPA is an estrogenic compound used to manufacture polycarbonate containers for food and drink, including baby bottles. It can migrate from container into foods, especially at elevated temperatures. Diet is a predominant source of exposure for phthalates and BPA, especially for infants. The aim of this study was to test the presence of DEHP, DnBP, and BPA in infant formulas. DEHP, DnBP, and BPA concentrations were measured in 22 liquid and 28 powder milks by gas chromatography with flame ionization detection and high performance liquid chromatography with fluorimetric detection, respectively. DEHP concentrations in our samples were between 0.005 and 5.088 μg/g (median 0.906 μg/g), DnBP concentrations were between 0.008 and 1.297 μg/g (median 0.053 μg/g), and BPA concentrations were between 0.003 and 0.375 μg/g (median 0.015 μg/g). Concentrations of the investigated contaminants in liquid and powder milks were not significantly different, even though samples were packed in different types of containers. These data point out potential hazards for infants fed with baby formulas. Contamination seems more related to the production of formulas than to a release from containers. PMID:25730646

  17. Cyclic Di-GMP Regulates Type IV Pilus-Dependent Motility in Myxococcus xanthus

    PubMed Central

    Skotnicka, Dorota; Petters, Tobias; Heering, Jan; Hoppert, Michael; Kaever, Volkhard

    2015-01-01

    ABSTRACT The nucleotide-based second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. Myxococcus xanthus undergoes major lifestyle changes in response to nutrient availability, with the formation of spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. Here, we investigated the function of c-di-GMP in M. xanthus and show that this bacterium synthesizes c-di-GMP during growth. Manipulation of the c-di-GMP level by expression of either an active, heterologous diguanylate cyclase or an active, heterologous phosphodiesterase correlated with defects in type IV pilus (T4P)-dependent motility, whereas gliding motility was unaffected. An increased level of c-di-GMP correlated with reduced transcription of the pilA gene (which encodes the major pilin of T4P), reduced the assembly of T4P, and altered cell agglutination, whereas a decreased c-di-GMP level correlated with altered cell agglutination. The systematic inactivation of the 24 genes in M. xanthus encoding proteins containing GGDEF, EAL, or HD-GYP domains, which are associated with c-di-GMP synthesis, degradation, or binding, identified three genes encoding proteins important for T4P-dependent motility, whereas all mutants had normal gliding motility. Purified DmxA had diguanylate cyclase activity, whereas the hybrid histidine protein kinases TmoK and SgmT, each of which contains a GGDEF domain, did not have diguanylate cyclase activity. These results demonstrate that c-di-GMP is important for T4P-dependent motility in M. xanthus. IMPORTANCE We provide the first direct evidence that M. xanthus synthesizes c-di-GMP and demonstrate that c-di-GMP is important for T4P-dependent motility, whereas we did not obtain evidence that c-di-GMP regulates gliding motility. The data presented uncovered a novel mechanism for regulation of T4P

  18. Diamidinium and iminium aromatics as new aggregators of the bacterial signaling molecule, c-di-GMP.

    PubMed

    Kelsey, Ilana; Nakayama, Shizuka; Sintim, Herman O

    2012-01-15

    C-di-GMP has emerged as an important bacterial signaling molecule that is involved in biofilm formation. Small molecules that can form biologically inactive complexes with c-di-GMP have the potential to be used as anti-biofilm agents. Herein, we report that water-soluble diamidinium/iminium aromatics (such as berenil), which are traditionally considered as minor groove binders of nucleic acids, are capable of aggregating c-di-GMP into G-quadruplexes via π-stacking interactions. PMID:22217869

  19. Fourier-transform infrared and Raman spectra, and ab initio calculations for cadmium- n-di-iso-propylphosphorylguanidine-di-chloride (CdDPGCl 2) complex

    NASA Astrophysics Data System (ADS)

    Téllez, Claudio A.; Hollauer, Eduardo; Felcman, Judith; Lopes, Damiana C. N.; Cattapan, Renata A.

    2002-07-01

    Cadmium- n-di-isopropylphosphorylguanidine-di-chloride (CdDPGCl 2) was synthesized in the solid phase and characterized previously. The Fourier transform infrared and Raman spectra of (CdDPGCl 2) in the solid state were recorded and analyzed. Emphasis was placed on the vibrational assignment of the [(O 2P=O{CdCl 2}HN=C)] fragment of the complete molecular structure. With the aim of assisting the vibrational assignment of the experimental spectra, a comparison with the spectra of N-di-isopropylphosphorylguanidine ligand was carried out and ab initio calculations have been performed with several effective core potentials and valence basis sets (Hay-Wadt (HW) and Stevens-Basch-Krauss (SBK)). Due to our limited computational resources, hydrogen atoms replaced the isopropyl groups. The calculated geometrical parameters showed excellent agreement with the experimental, as well as the RHF/MP2 calculated infrared wave numbers, when compared to the IR/Raman experimental wave numbers.

  20. DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE

    EPA Science Inventory

    DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE. JE Andrews, H Nichols, and ES Hunter. Reproductive Toxicology Division, NHEERL, USEPA, RTP, NC.

    Disinfection of drinking water with chlorine results in numerous chlorinated byprodu...

  1. A new di-ruthenium complex with an intense near-infrared electronic band

    SciTech Connect

    Spreer, L.O.; Allen, C.B.; MacQueen, D.B.; Calvin, M.; Otvos, J.W.

    1993-12-31

    A new di-ruthenium complex prepared by the aerobic oxidation of trans Ru(1,4,7,11-tetraazacyclo-tetradecane) Cl{sub 2} has been investigated. The FAB mass spectrum shows mass peaks centered at m/z 732 and the isotopic ion distribution pattern gives the composition C{sub 20}H{sub 36}N{sub 8}Cl{sub 4}Ru{sub 2}. This paper gives evidence supporting characterization of this species as the ruthenium analogue of a di-iron complex with a delocalized pi system (Inorg. Chem. 1992, 31, 717) bridging two tetraazamacrocycles. The di-ruthenium complex, like the di-iron has a very intense electronic transition in the near-infrared.

  2. The oxidation of 2,6-di-tert-butyl-4-methylphenol

    USGS Publications Warehouse

    Yohe, G.R.; Dunbar, J.E.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.

    1956-01-01

    The products formed in the oxidation of 2,6-di-tert-butyl-4-methylphenol with oxygen and sodium hydroxide at about 100?? are 3,5-di-tert-butyl-4-hydroxybenzaldehyde, trimethylacetic acid, an acidic compound C14H22O3, and probably 2,6-di-tert-butylbenzoquinone (which was actually isolated in the similar oxidation of the above-named benzaldehyde), in addition to compounds previously reported. Some of the properties of C14H22O3 are given, and the oxidation of it to 2,3-di-tert-butylsuccinic anhydride is described, but assignment of structure is reserved pending the completion of more experimental work.

  3. The expanding roles of c-di-GMP in the biosynthesis of exopolysaccharides and secondary metabolites.

    PubMed

    Liang, Zhao-Xun

    2015-05-01

    The cyclic dinucleotide c-di-GMP has emerged in the last decade as a prevalent intracellular messenger that orchestrates the transition between the motile and sessile lifestyles of many bacterial species. The motile-to-sessile transition is often associated with the formation of extracellular matrix-encased biofilm, an organized community of bacterial cells that often contributes to antibiotic resistance and host-pathogen interaction. It is increasingly clear that c-di-GMP controls motility, biofilm formation and bacterial pathogenicity partially through regulating the production of exopolysaccharides (EPS) and small-molecule secondary metabolites. This review summarizes our current understanding of the regulation of EPS biosynthesis by c-di-GMP in a diversity of bacterial species and highlights the emerging role of c-di-GMP in the biosynthesis of small-molecule secondary metabolites.

  4. Di-jet production and angular correlations in DIS at NLO

    NASA Astrophysics Data System (ADS)

    Jalilian-Marian, Jamal

    2016-03-01

    Angular correlations are a sensitive probe of the dynamics of QCD at high energy. In particular azimuthal angular correlations between two hadrons produced in Deeply Inelastic Scattering (DIS) of a virtual photon on a hadron or nucleus offer the best environment in which to investigate high gluon density (gluon saturation) effects expected to arise at small x. Here we give a progress report on our derivation of Next to Leading Order (NLO) corrections to di-jet (di-hadron) production in DIS.

  5. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers.

    PubMed

    Hengge, Regine; Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2016-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany)brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i)c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology,with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

  6. Cyclic-di-GMP signalling regulates motility and biofilm formation in Bordetella bronchiseptica

    PubMed Central

    Sisti, Federico; Ha, Dae-Gon; O'Toole, George A.; Hozbor, Daniela

    2013-01-01

    The signalling molecule bis-(3′–5′)-cyclic-dimeric guanosine monophosphate (c-di-GMP) is a central regulator of diverse cellular functions, including motility, biofilm formation, cell cycle progression and virulence, in bacteria. Multiple diguanylate cyclase and phosphodiesterase-domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) modulate the levels of the second messenger c-di-GMP to transmit signals and obtain such specific cellular responses. In the genus Bordetella this c-di-GMP network is poorly studied. In this work, we evaluated the expression of two phenotypes in Bordetella bronchiseptica regulated by c-di-GMP, biofilm formation and motility, under the influence of ectopic expression of Pseudomonas aeruginosa proteins with EAL or GGDEF domains that regulates the c-di-GMP level. In agreement with previous reports for other bacteria, we observed that B. bronchiseptica is able to form biofilm and reduce its motility only when GGDEF domain protein is expressed. Moreover we identify a GGDEF domain protein (BB3576) with diguanylate cyclase activity that participates in motility and biofilm regulation in B. bronchiseptica. These results demonstrate for the first time, to our knowledge, the presence of c-di-GMP regulatory signalling in B. bronchiseptica. PMID:23475948

  7. Structural Basis for c-di-GMP-Mediated Inside-Out Signaling Controlling Periplasmic Proteolysis

    PubMed Central

    Madden, Dean R.; O'Toole, George A.; Sondermann, Holger

    2011-01-01

    The bacterial second messenger bis-(3′–5′) cyclic dimeric guanosine monophosphate (c-di-GMP) has emerged as a central regulator for biofilm formation. Increased cellular c-di-GMP levels lead to stable cell attachment, which in Pseudomonas fluorescens requires the transmembrane receptor LapD. LapD exhibits a conserved and widely used modular architecture containing a HAMP domain and degenerate diguanylate cyclase and phosphodiesterase domains. c-di-GMP binding to the LapD degenerate phosphodiesterase domain is communicated via the HAMP relay to the periplasmic domain, triggering sequestration of the protease LapG, thus preventing cleavage of the surface adhesin LapA. Here, we elucidate the molecular mechanism of autoinhibition and activation of LapD based on structure–function analyses and crystal structures of the entire periplasmic domain and the intracellular signaling unit in two different states. In the absence of c-di-GMP, the intracellular module assumes an inactive conformation. Binding of c-di-GMP to the phosphodiesterase domain disrupts the inactive state, permitting the formation of a trans-subunit dimer interface between adjacent phosphodiesterase domains via interactions conserved in c-di-GMP-degrading enzymes. Efficient mechanical coupling of the conformational changes across the membrane is realized through an extensively domain-swapped, unique periplasmic fold. Our structural and functional analyses identified a conserved system for the regulation of periplasmic proteases in a wide variety of bacteria, including many free-living and pathogenic species. PMID:21304926

  8. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers

    PubMed Central

    Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2015-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

  9. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication.

    PubMed

    Lori, C; Ozaki, S; Steiner, S; Böhm, R; Abel, S; Dubey, B N; Schirmer, T; Hiller, S; Jenal, U

    2015-07-01

    Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division with cell fate decisions, equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.

  10. 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.

  11. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers.

    PubMed

    Hengge, Regine; Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2016-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany)brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i)c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology,with major impacts in research fields ranging from human health to microbial ecology.

  12. Identification of ligand analogues that control c-di-GMP riboswitches.

    PubMed

    Furukawa, Kazuhiro; Gu, Hongzhou; Sudarsan, Narasimhan; Hayakawa, Yoshihiro; Hyodo, Mamoru; Breaker, Ronald R

    2012-08-17

    Riboswitches for the bacterial second messenger c-di-GMP control the expression of genes involved in numerous cellular processes such as virulence, competence, biofilm formation, and flagella synthesis. Therefore, the two known c-di-GMP riboswitch classes represent promising targets for developing novel modulators of bacterial physiology. Here, we examine the binding characteristics of circular and linear c-di-GMP analogues for representatives of both class I and II c-di-GMP riboswitches derived from the pathogenic bacterium Vibrio choleae (class I) and Clostridium difficile (class II). Some compounds exhibit values for apparent dissociation constant (K(D)) below 1 μM and associate with riboswitch RNAs during transcription with a speed that is sufficient to influence riboswitch function. These findings are consistent with the published structural models for these riboswitches and suggest that large modifications at various positions on the ligand can be made to create novel compounds that target c-di-GMP riboswitches. Moreover, we demonstrate the potential of an engineered allosteric ribozyme for the rapid screening of chemical libraries for compounds that bind c-di-GMP riboswitches. PMID:22646696

  13. Cyclic-di-GMP signalling regulates motility and biofilm formation in Bordetella bronchiseptica.

    PubMed

    Sisti, Federico; Ha, Dae-Gon; O'Toole, George A; Hozbor, Daniela; Fernández, Julieta

    2013-05-01

    The signalling molecule bis-(3'-5')-cyclic-dimeric guanosine monophosphate (c-di-GMP) is a central regulator of diverse cellular functions, including motility, biofilm formation, cell cycle progression and virulence, in bacteria. Multiple diguanylate cyclase and phosphodiesterase-domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) modulate the levels of the second messenger c-di-GMP to transmit signals and obtain such specific cellular responses. In the genus Bordetella this c-di-GMP network is poorly studied. In this work, we evaluated the expression of two phenotypes in Bordetella bronchiseptica regulated by c-di-GMP, biofilm formation and motility, under the influence of ectopic expression of Pseudomonas aeruginosa proteins with EAL or GGDEF domains that regulates the c-di-GMP level. In agreement with previous reports for other bacteria, we observed that B. bronchiseptica is able to form biofilm and reduce its motility only when GGDEF domain protein is expressed. Moreover we identify a GGDEF domain protein (BB3576) with diguanylate cyclase activity that participates in motility and biofilm regulation in B. bronchiseptica. These results demonstrate for the first time, to our knowledge, the presence of c-di-GMP regulatory signalling in B. bronchiseptica.

  14. Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase.

    PubMed

    Kim, Hyo Jung; Kim, Jin Sook; Woo, Je-Tae; Lee, Ik-Soo; Cha, Byung-Yoon

    2015-07-01

    Methyl 3,5-di-caffeoylquinate (3,5-diCQM) has been used for the treatment of various diseases in oriental medicine, but its effect on melanogenesis has not been reported yet. In this study, the molecular mechanism of 3,5-diCQM-induced melanogenesis was investigated. It was found that 3,5-diCQM induced synthesis of melanin pigments in murine B16F10 melanoma cells in a concentration-dependent manner. Treatment of cells with 3,5-diCQM for 48 h increased extracellular and intracellular melanin production and tyrosinase activity. The expressions of tyrosinase, tyrosinase-related protein 1 (TRP1), and TRP2 were up-regulated in a dose-dependent manner 48 h after 3,5-diCQM treatment. Western blot analysis showed that 3,5-diCQM increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP responsive element binding as well as the expression of microphthalmia-associated transcription factor. In addition, 3,5-diCQM-stimulated cAMP production, and 3,5-diCQM-induced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results suggested that 3,5-diCQM-mediated activation of the p38 pathway may represent a novel approach for an effective therapy for vitiligo and hair graying. PMID:26018825

  15. An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence

    PubMed Central

    Huynh, TuAnh Ngoc; Luo, Shukun; Pensinger, Daniel; Sauer, John-Demian; Tong, Liang; Woodward, Joshua J.

    2015-01-01

    The nucleotide cyclic di-3′,5′- adenosine monophosphate (c-di-AMP) was recently identified as an essential and widespread second messenger in bacterial signaling. Among c-di-AMP–producing bacteria, altered nucleotide levels result in several physiological defects and attenuated virulence. Thus, a detailed molecular understanding of c-di-AMP metabolism is of both fundamental and practical interest. Currently, c-di-AMP degradation is recognized solely among DHH-DHHA1 domain-containing phosphodiesterases. Using chemical proteomics, we identified the Listeria monocytogenes protein PgpH as a molecular target of c-di-AMP. Biochemical and structural studies revealed that the PgpH His-Asp (HD) domain bound c-di-AMP with high affinity and specifically hydrolyzed this nucleotide to 5′-pApA. PgpH hydrolysis activity was inhibited by ppGpp, indicating a cross-talk between c-di-AMP signaling and the stringent response. Genetic analyses supported coordinated regulation of c-di-AMP levels in and out of the host. Intriguingly, a L. monocytogenes mutant that lacks c-di-AMP phosphodiesterases exhibited elevated c-di-AMP levels, hyperinduced a host type-I IFN response, and was significantly attenuated for infection. Furthermore, PgpH homologs, which belong to the 7TMR-HD family, are widespread among hundreds of c-di-AMP synthesizing microorganisms. Thus, PgpH represents a broadly conserved class of c-di-AMP phosphodiesterase with possibly other physiological functions in this crucial signaling network. PMID:25583510

  16. Francium sources at Laboratori Nazionali di Legnaro: Design and performance

    SciTech Connect

    Stancari, G.; Veronesi, S.; Corradi, L.; Atutov, S.N.; Calabrese, R.; Dainelli, A.; Mariotti, E.; Moi, L.; Sanguinetti, S.; Tomassetti, L.

    2006-03-15

    A facility for the production of radioactive francium is operating at the laboratories of the Istituto Nazionale di Fisica Nucleare (INFN) in Legnaro, Italy. The goal is to collect a cold sample of radioactive atoms in a magneto-optical trap for studies in atomic, nuclear, and particle physics. Production of francium is achieved via the fusion-evaporation reaction {sup 197}Au({sup 18}O,kn){sup 215-k}Fr generated by a {approx}100-MeV {sup 18}O{sup 6+} beam on a thick gold target. The production target is heated to {approx}1200 K and kept at a potential of +3 kV to enhance Fr diffusion and surface desorption. Average production rates are 0.7x10{sup 6} ions/s for {sup 210}Fr with a primary beam flux of 10{sup 12} particles/s, with peaks of 2x10{sup 6} ions/s. Details are given on the design and construction of the production targets and on the measurements that characterize their performance.

  17. A purple acidophilic di-ferric DNA ligase from Ferroplasma.

    PubMed

    Ferrer, Manuel; Golyshina, Olga V; Beloqui, Ana; Böttger, Lars H; Andreu, José M; Polaina, Julio; De Lacey, Antonio L; Trautwein, Alfred X; Timmis, Kenneth N; Golyshin, Peter N

    2008-07-01

    We describe here an extraordinary purple-colored DNA ligase, LigFa, from the acidophilic ferrous iron-oxidizing archaeon Ferroplasma acidiphilum, a di-ferric enzyme with an extremely low pH activity optimum. Unlike any other DNA ligase studied to date, LigFa contains two Fe(3+)-tyrosinate centers and lacks any requirement for either Mg(2+) or K(+) for activity. DNA ligases from closest phylogenetic and ecophysiological relatives have normal pH optima (6.0-7.5), lack iron, and require Mg(2+)/K(+) for activity. Ferric iron retention is pH-dependent, with release resulting in partial protein unfolding and loss of activity. Reduction of the Fe(3+) to Fe(2+) results in an 80% decrease in DNA substrate binding and an increase in the pH activity optimum to 5.0. DNA binding induces significant conformational change around the iron site(s), suggesting that the ferric irons of LigFa act both as structure organizing and stabilizing elements and as Lewis acids facilitating DNA binding at low pH.

  18. Francium sources at Laboratori Nazionali di Legnaro: Design and performance

    NASA Astrophysics Data System (ADS)

    Stancari, G.; Veronesi, S.; Corradi, L.; Atutov, S. N.; Calabrese, R.; Dainelli, A.; Mariotti, E.; Moi, L.; Sanguinetti, S.; Tomassetti, L.

    2006-03-01

    A facility for the production of radioactive francium is operating at the laboratories of the Istituto Nazionale di Fisica Nucleare (INFN) in Legnaro, Italy. The goal is to collect a cold sample of radioactive atoms in a magneto-optical trap for studies in atomic, nuclear, and particle physics. Production of francium is achieved via the fusion-evaporation reaction Au197(O18,kn)215-kFr generated by a ˜100-MeV O6+18 beam on a thick gold target. The production target is heated to ˜1200K and kept at a potential of +3kV to enhance Fr diffusion and surface desorption. Average production rates are 0.7×106ions/s for Fr210 with a primary beam flux of 1012particles/s, with peaks of 2×106ions/s. Details are given on the design and construction of the production targets and on the measurements that characterize their performance.

  19. Biotransformation of di(2-ethylhexyl)phthalate by rainbow trout

    SciTech Connect

    Barron, M.G.; Hayton, W.L.

    1995-05-01

    The biotransformation of di(2-ethylhexyl)phthalate (DEHP) was studied in rainbow trout (Oncorhynchus mykiss) following intravascular administration. Methyl-esterified metabolites were identified using rodent-derived standards and non-linear gradient elution HPLC; metabolites were confirmed by gas chromatography. Similarities between the biotransformation of DEHP by rainbow trout and mammalian species included (a) mono-ethylhexyl phthalate (MEHP) appeared to be the obligatory first step in DEHP metabolism; (b) the phthalate ring was not oxidized; (c) phthalic acid was a minor metabolite; and (d) several metabolites contained multiple oxidations of the 2-ethylhexyl moiety of MEHP. No metabolites unique to rainbow trout were identified. However, fewer oxidized metabolites were identified in rainbow trout than in mammalian species, possibly due to limited mitochondrial metabolism of MEHP in rainbow trout. The amount of biliary MEHP glucuronide after intravascular administration of DEHP was substantially less than reported in rainbow trout exposed to DEHP via the water. Results confirmed that DEHP metabolism in rainbow trout proceeds by initial rapid formation of MEHP, followed by excretion or extensive oxidation by microsomal P450.

  20. Di-electron and two-photon widths in charmonium

    SciTech Connect

    Badalian, A. M.; Danilkin, I. V.

    2009-07-15

    The vector and pseudoscalar decay constants are calculated in the framework of the Field Correlator Method. Di-electron widths: {Gamma}{sub ee}(J/{psi}) = 5.41 keV, {Gamma}{sub ee}({psi}'(3686)) = 2.47 keV, {Gamma}{sub ee}({psi}''(3770)) = 0.248 keV, in good agreement with experiment, are obtained with the same coupling, {alpha}{sub s} = 0.165, in the QCD radiative corrections. We show that the larger {alpha}{sub s} = 0.191 {+-} 0.004 is needed to reach agreement with experiment for {Gamma}{sub {gamma}{gamma}}({chi}c) = 7.22 keV, {Gamma}{sub {gamma}{gamma}}({chi}c({sup 3}P0)) = 3.3 keV, {Gamma}{sub {gamma}{gamma}}{chi}c({sup 3}P{sub 2}) = 0.54 keV, and also for {Gamma}(J/{psi} {yields} 3g) = 59.5 keV, {Gamma}(J/{psi} {yields} {gamma}2g) = 5.7 keV. Meanwhile, even larger {alpha}{sub s} = 0.238 gives rise to good description of {Gamma}({psi}' {yields} 3g) = 52.7 keV, {Gamma}({psi}' {yields} {gamma} 2g) = 3.5 keV, and provides correct ratio of the branching fractions: {Beta} (J/{psi} {yields} light hadrons)/{Beta} ({psi}' {yields} light hadrons) = 0.24.

  1. Forward di-jet production in dilute-dense collisions

    NASA Astrophysics Data System (ADS)

    Petreska, E.; Kotko, P.; Kutak, K.; Marquet, C.; Sapeta, S.; van Hameren, A.

    2016-03-01

    We derive a factorization formula for forward production of two jets in dilutedense collisions that is valid for an arbitrary value of the momentum imbalance of the jets, kt. This generalizes the transverse momentum dependent (TMD) factorization formula that has been derived before by Dominguez et al. Their formula is valid only for small values of the transverse momentum of the small-x gluon from the target; it has kt dependent TMD gluon distributions, but on-shell hard matrix elements. We extend the TMD formula to all ranges of kt by including off-shell matrix elements. We also add finite Nc corrections. The new formula encompasses both, the TMD factorization for small kt on the order of the saturation scale, and the High Energy Factorization (HEF) for large kt on the order of the momentum of the jets. The TMD and HEF factorizations can be derived from the Color Glass Condensate (CGC) formula for forward di-jet production in the appropriate limits. We show explicitly the equivalence of HEF and CGC in the dilute target approximation.

  2. Crystal structure of creatininium 5-(2,4-di-nitro-phen-yl)-1,3-di-methyl-barbiturate monohydrate: a potential anti-convulsant agent.

    PubMed

    Poornima Devi, Ponnusamy; Kalaivani, Doraisamyraja

    2016-05-01

    In the anion of the title hydrated mol-ecular salt, C4H8N3O(+)·C12H9N4O7 (-)·H2O [systematic name: 2-amino-1-methyl-4-oxo-4,5-di-hydro-1H-imidazol-3-ium 5-(2,4-di-nitro-phen-yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetra-hydro-pyrimidin-4-olate monohydrate], the 2,4-di-nitro-phenyl ring is inclined to the mean plane of the pyrimidine ring [r.m.s. deviation = 0.37 Å] by 43.24 (8)°. The five-membered ring of the creatininium cation (2-amino-1-methyl-4-oxo-4,5-di-hydro-1H-imidazol-3-ium) is essentially planar with an r.m.s. deviation of 0.015 Å. In the crystal, the anions and cations are linked via N-H⋯O hydrogen bonds, forming sheets parallel to the ab plane. The sheets are linked via O-H⋯O hydrogen bonds involving the water mol-ecule, forming a three-dimensional framework. Within the framework, there are C-H⋯O hydrogen bonds present. The title mol-ecular salt displays anti-convulsant and hypnotic activities. PMID:27308003

  3. 3,6-diHydroxyflavone/bovine serum albumin interaction in cyclodextrin medium: Absorption and emission monitoring

    NASA Astrophysics Data System (ADS)

    Voicescu, Mariana; Bandula, Rodica

    2015-03-01

    Photophysical properties of a bioactive flavonol which can be used as a model for polyhydroxylated natural flavonols, 3,6-diHydroxyflavone (3,6-diHF) in cyclodextrins (CDs)/bovine serum albumin (BSA) systems have been studied by absorption and fluorescence spectroscopy. The influence of CDs nature and of the different molar ratios BSA/CDs on the fluorescent characteristics of 3,6-diHF, and on the excited - state intramolecular proton transfer (ESIPT) process were studied. Quantitative information on the interaction between 3,6-diHF and BSA in CDs medium, were estimated. The influence of temperature (25-60 °C range) on the intrinsic fluorescence of BSA in 3,6-diHF/BSA/CDs systems, was investigated. The results are discussed with relevance to 3,6-diHF as a potential sensitive fluorescence probe in the systems of biological interest.

  4. [Relationship between geopolitical political structure and distribution of dao-di herbs in frontier provinces of China].

    PubMed

    Peng, Hua-Sheng; Hao, Jin-Da; Huang, Lu-Qi

    2013-09-01

    Dao-di herbs have both natural and humanistic attribute. Geopolitical political structure of Northeast, Mongolian, Xinjiang, Tibet, Yunnan and Guangxi provinces form frontier inland of China were summarized in this paper. The relationship between distribution of the Dao-di herbs and geopolitical political structure in above-mentioned provinces were described. In a strict sense, humanistic attribute of Dao-di herbs belonged to medical culture of Han Nationality. Distribution range of Dao-di herbs was determined by sphere of influence of central plains dynasty. Development of Dao-di herbs in the frontier inland area was unbalanced. The relationship between distribution of Dao-di herbs and geopolitical political structure proofed that natural attribute and humanistic attribute were inseparable. Recognition of this relationship is helpful to understand and develop genuine medicinal materials in frontier provinces.

  5. High Stabilities of Di(1-azulenyl)(4-hydroxyphenyl)methyl Hexafluorophosphates and Polarized Properties of alpha,alpha-Di(1-azulenyl)-1,4-benzoquinone Methides.

    PubMed

    Ito, Shunji; Kikuchi, Shigeru; Kobayashi, Hiroki; Morita, Noboru; Asao, Toyonobu

    1997-04-18

    Acid-catalyzed condensation of azulenes 8a-c with 4-hydroxy- and 3,5-di-tert-butyl-4-hydroxybenzaldehyde leads to substituted di(1-azulenyl)(4-hydroxy- and 3,5-di-tert-butyl-4-hydroxyphenyl)methanes 7a- f, which are easily converted into substituted di(1-azulenyl)(4-hydroxy- and 3,5-di-tert-butyl-4-hydroxyphenyl)methyl cations 5a-f by oxidation with DDQ. The spectroscopic data are consistent with the protonated cationic structures of 5a-f. The electrochemical reduction of 5a-f showed a reversible wave at -0.74 to -0.86 V (V vs Ag/Ag(+)) upon cyclic voltammetry (CV), although 5d and 5e showed an irreversible wave at -0.79 V. The relatively high reduction potentials of 5a-f, compared with those of di(1-azulenyl)phenylmethyl cations 2a-c, exhibit the stabilization by 4-hydroxy substituents on the phenyl groups. These salts (5a-f.PF(6)(-)) bearing 4-hydroxyl groups on the phenyl rings have been converted by treatment with bases to alpha,alpha-di(1-azulenyl)-1,4-benzoquinone methides 6a-f, which revert to 5a-f.PF(6)(-) upon reprotonation with HPF(6). These quinone methides (6a-f) are highly polarized by the extreme-electrodonating properties of 1-azulenyl groups. The highly polarized properties of 6a-f reflected to the high pK(a) values of their conjugate acids (5a-c, 6.5-7.1, and 5d-f, 3.4-3.8). The strong solvatochromic effects also provide strong evidence of a large contribution of dipolar forms (6') in the ground state. The relatively low oxidation potentials of 6a-f (+0.35 to +0.47 V vs Ag/Ag(+)) reflected facile formation of phenoxy radical cations, stabilized by two 1-azulenyl groups. PMID:11671576

  6. 6,8-Di-C-methyl-flavonoids with neuroprotective activities from Rhododendron fortunei.

    PubMed

    Lai, Yongji; Zeng, Hong; He, Meijun; Qian, Huiqin; Wu, Zhaodi; Luo, Zengwei; Xue, Yongbo; Yao, Guangmin; Zhang, Yonghui

    2016-07-01

    Six 6,8-di-C-methyl-flavonoids, (2R,3R)-6,8-di-C-methyl-5,7,4'-trihydroxyflavanonol 7-O-β-d-gluco-pyranoside (1), (2R,3R)-6,8-di-C-methyl-5,7,4'-trihydroxyflavanonol 7-O-β-d-xylopyranosyl(1→6)-β-d-glucopyranoside (2), 6,8-di-C-methylkaempferol 7-O-β-d-glucopyranoside (3), (2R)-farrerol (4a), (2R/2S)-farrerol 7-O-β-d-glucopyranoside (5), and (2R/2S)-farrerol 7-O-β-d-xylopyranosyl(1→6)-β-d-glucopyranoside (6), and four known analogues, farrerol (4b), (2R,3R)-6,8-di-C-methyldihydrokae-mpferol (7), 6,8-di-C-methylkaempferol 7-O-β-d-glucopyranoside (8), and 6,8-di-C-methylkaempferol (9), were isolated from the twigs and leaves of Rhododendron fortunei. The structures of compounds 1-9 were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and CD) and chemical methods. Compounds 1-9 were evaluated for their neuroprotective effects on the human neuroblastoma SH-SY5Y cells apoptosis induced by hydrogen peroxide (H2O2) and amyloid β peptide (Aβ), respectively. Compounds 1-3 and 5-9 exhibited significant neuroprotective effects against H2O2-induced SH-SY5Y cell apoptosis, and compound 8 exhibited the strongest activity with a improvement of cell viability by about 30% at the concentration of 10μM. Compounds 1-9 showed significant neuroprotective effects against Aβ-induced SH-SY5Y cell apoptosis. PMID:27345941

  7. Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

    PubMed Central

    Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2016-01-01

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

  8. DhhP, a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi, Is Essential for Cell Growth and Virulence

    PubMed Central

    Ye, Meiping; Zhang, Jun-Jie; Fang, Xin; Lawlis, Gavin B.; Troxell, Bryan; Zhou, Yan; Gomelsky, Mark

    2014-01-01

    Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn2+- or Mg2+-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP's functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σS factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence. PMID:24566626

  9. Boosted di-boson from a mixed heavy stop

    SciTech Connect

    Ghosh, Diptimoy

    2013-12-01

    The lighter mass eigenstate ($\\widetilde{t}_1$) of the two top squarks, the scalar superpartners of the top quark, is extremely difficult to discover if it is almost degenerate with the lightest neutralino ($\\widetilde{\\chi}_1^0$), the lightest and stable supersymmetric particle in the R-parity conserving supersymmetry. The current experimental bound on $\\widetilde{t}_1$ mass in this scenario stands only around 200 GeV. For such a light $\\widetilde{t}_1$, the heavier top squark ($\\widetilde{t}_2$) can also be around the TeV scale. Moreover, the high value of the higgs ($h$) mass prefers the left and right handed top squarks to be highly mixed allowing the possibility of a considerable branching ratio for $\\widetilde{t}_2 \\to \\widetilde{t}_1 h$ and $\\widetilde{t}_2 \\to \\widetilde{t}_1 Z$. In this paper, we explore the above possibility together with the pair production of $\\widetilde{t}_2$ $\\widetilde{t}_2^*$ giving rise to the spectacular di-boson + missing transverse energy final state. For an approximately 1 TeV $\\widetilde{t}_2$ and a few hundred GeV $\\widetilde{t}_1$ the final state particles can be moderately boosted which encourages us to propose a novel search strategy employing the jet substructure technique to tag the boosted $h$ and $Z$. The reconstruction of the $h$ and $Z$ momenta also allows us to construct the stransverse mass $M_{T2}$ providing an additional efficient handle to fight the backgrounds. We show that a 4--5$\\sigma$ signal can be observed at the 14 TeV LHC for $\\sim$ 1 TeV $\\widetilde{t}_2$ with 100 fb$^{-1}$ integrated luminosity.

  10. A minimalist biosensor: Quantitation of cyclic di-GMP using the conformational change of a riboswitch aptamer

    PubMed Central

    Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C

    2015-01-01

    Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA. PMID:26114964

  11. Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain

    PubMed Central

    Wang, Yu-Chuan; Chin, Ko-Hsin; Tu, Zhi-Le; He, Jin; Jones, Christopher J.; Sanchez, David Zamorano; Yildiz, Fitnat H.; Galperin, Michael Y.; Chou, Shan-Ho

    2016-01-01

    C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date. PMID:27578558

  12. Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.

    PubMed

    Wang, Yu-Chuan; Chin, Ko-Hsin; Tu, Zhi-Le; He, Jin; Jones, Christopher J; Sanchez, David Zamorano; Yildiz, Fitnat H; Galperin, Michael Y; Chou, Shan-Ho

    2016-01-01

    C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date. PMID:27578558

  13. Di-(2-ethylhexyl) adipate and 20 phthalates in composite food samples from the 2013 Canadian Total Diet Study.

    PubMed

    Cao, Xu-Liang; Zhao, Wendy; Dabeka, Robert

    2015-01-01

    A sensitive and selective GC-MS method was developed and used for simultaneous analysis of di-(2-ethylhexyl) adipate (DEHA) and 20 selected phthalates in the food samples from the 2013 Canadian Total Diet Study. At least one of the 21 target chemicals was detected in 141 of the 159 different food composite samples analysed. However, only seven of the 21 target chemicals were detected, with di-(2-ethylhexyl) phthalate (DEHP) and DEHA being detected most frequently, in 111 and 91 different food composite samples, respectively, followed by di-n-butyl phthalate (DBP) (n = 44), n-butyl benzyl phthalate (BBzP) (32), di-iso-butyl phthalate (DiBP) (27), di-ethyl phthalate (DEP) (3), and di-cyclohexyl phthalate (DCHP) (1). Levels of DEP (di-ethyl phthalate), DiBP, DBP, BBzP and DCHP were low, in general, with average concentrations of 9.63, 8.26, 23.2, 12.4 and 64.9 ng g(-1), respectively. Levels of DEHA and DEHP varied widely, ranging from 1.4 to 6010 ng g(-1) and from 14.4 to 714 ng g(-1), respectively. High levels of DEHA were found mainly in the composite samples where the individual food items used to prepare the composite were likely packaged in polyvinyl chloride (PVC) wrapping film, while the highest DEHP levels were found in the vegetable and fruit samples.

  14. Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.

    PubMed

    Wang, Yu-Chuan; Chin, Ko-Hsin; Tu, Zhi-Le; He, Jin; Jones, Christopher J; Sanchez, David Zamorano; Yildiz, Fitnat H; Galperin, Michael Y; Chou, Shan-Ho

    2016-01-01

    C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date.

  15. Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma.

    PubMed

    Nakamura, Takashi; Miyabe, Hiroko; Hyodo, Mamoru; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi

    2015-10-28

    Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC-I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated within YSK05-liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c-di-GMP/YSK05-Lip induces MHC-I non-restricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas.

  16. A minimalist biosensor: Quantitation of cyclic di-GMP using the conformational change of a riboswitch aptamer.

    PubMed

    Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C

    2015-01-01

    Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA.

  17. Diethyl 4-(2-meth-oxy-phen-yl)-2,6-di-methyl-1,4-di-hydro-pyridine-3,5-di-carboxyl-ate.

    PubMed

    Wang, Ke; Wang, Yifeng; Yao, Minjie; Xu, Danqian

    2013-05-01

    In the title compound, C20H25NO5, the di-hydro-pyridine ring adopts a flattened boat conformation. The meth-oxy-phenyl ring is almost perpendicular to the mean plane of the pyridine ring [dihedral angle = 88.42 (3)°]. The two carbonyl units adopt a synperiplanar conformation with respect to the double bonds in the di-hydro-pyridine ring. In the crystal, mol-ecules are connected by N-H⋯O hydrogen bonds into R 4 (4)(24) tetra-meric rings. A region of disordered electron density, located at the center of four adjacent mol-ecules, was treated with the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]. It is probably the result of traces of the solvent of crystallization and was not taken into account during the structure refinement. PMID:23723929

  18. 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

  19. 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

  20. 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.

  1. Cyclic di-GMP sensing via the innate immune signaling protein STING.

    PubMed

    Yin, Qian; Tian, Yuan; Kabaleeswaran, Venkataraman; Jiang, Xiaomo; Tu, Daqi; Eck, Michael J; Chen, Zhijian J; Wu, Hao

    2012-06-29

    Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an α + β fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.

  2. Indirect constraints on the scalar di-photon resonance at the LHC

    NASA Astrophysics Data System (ADS)

    Goertz, Florian; Kamenik, Jernej F.; Katz, Andrey; Nardecchia, Marco

    2016-05-01

    Motivated by the tantalizing excesses recently reported in the di-photon invariant mass spectrum at the LHC, we scrutinize some implications of scalar di-photon resonances in high energy proton-proton collisions. In particular, indications of a large width impose several challenges for model building. We show how calculability and unitarity considerations severely limit possible perturbative realizations of such a signal and propose a simple criterion that can be adapted to any renormalizable model. Furthermore, we discuss correlations between a di-photon excess and precision observables, including the anomalous magnetic and electric dipole moments of quarks and leptons, neutral meson oscillations and radiative flavor changing neutral current mediated decays of heavy leptons and hadrons. We find that existing searches and measurements significantly constrain the possibilities for a scalar resonance decaying into final states involving Standard Model fermions. We propose future search strategies which could elucidate some remaining currently unconstrained decay channels and discuss possible correlations between the di-photon excess and several recently reported flavor anomalies, showing that the latter can be addressed in a new incarnation of a gauged U(1)' model, with the di-photon resonance being the physical remnant of the U(1)'-breaking field.

  3. Structural Insight into the Mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.

    SciTech Connect

    Tchigvintsev, A.; Xu, X.; Singer, A.; Chang, C.; Brown, G.; Proudfoot, M.; Cui, H.; Flick, R.; Anderson, W.; Joachimiak, A.; Galperin, M.; Savchenko, A.; Yakunin, A.; Biosciences Division; Univ. of Toronto; Northwestern Univ.; NIH

    2010-08-01

    Cyclic diguanylate (or bis-(3'-5') cyclic dimeric guanosine monophosphate; c-di-GMP) is a ubiquitous second messenger that regulates diverse cellular functions, including motility, biofilm formation, cell cycle progression, and virulence in bacteria. In the cell, degradation of c-di-GMP is catalyzed by highly specific EAL domain phosphodiesterases whose catalytic mechanism is still unclear. Here, we purified 13 EAL domain proteins from various organisms and demonstrated that their catalytic activity is associated with the presence of 10 conserved EAL domain residues. The crystal structure of the TBD1265 EAL domain was determined in free state (1.8 {angstrom}) and in complex with c-di-GMP (2.35 {angstrom}), and unveiled the role of conserved residues in substrate binding and catalysis. The structure revealed the presence of two metal ions directly coordinated by six conserved residues, two oxygens of c-di-GMP phosphate, and potential catalytic water molecule. Our results support a two-metal-ion catalytic mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.

  4. Crystal and molecular structure of the sulfhydryl protease calotropin DI at 3.2 A resolution.

    PubMed

    Heinemann, U; Pal, G P; Hilgenfeld, R; Saenger, W

    1982-11-15

    The three-dimensional structure of the sulfhydryl protease calotropin DI from the madar plant, Calotropis gigantea, has been determined at 3.2 A resolution using the multiple isomorphous replacement method with five heavy atom derivatives. A Fourier synthesis based on protein phases with a mean figure of merit of 0.857 was used for model building. The polypeptide backbone of calotropin DI is folded to form two distinct lobes, one of which is comprised mainly of alpha-helices, while the other is characterized by a system of all antiparallel pleated sheets. The overall molecular architecture closely resembles those found in the sulfhydryl proteases papain and actinidin. Despite the unknown amino acid sequence of calotropin DI a number of residues around its active center could be identified. These amino acid side-chains were found in a similar arrangement as the corresponding ones in papain and actinidin. The polypeptide chain between residues 1 and 18 of calotropin DI folds in a unique manner, providing a possible explanation for the unusual inability of calotropin DI to hydrolyze those synthetic substrates that papain and actinidin act upon.

  5. NXT:1980Di immersion scanner for 7nm and 5nm production nodes

    NASA Astrophysics Data System (ADS)

    de Graaf, Roelof; Weichselbaum, Stefan; Droste, Richard; McLaren, Matthew; Koek, Bert; de Boeij, Wim

    2016-03-01

    Immersion scanners remain the critical lithography workhorses in semiconductor device manufacturing. When progressing towards the 7nm device node for logic and D18 device node for DRAM production, pattern-placement and layer-to-layer overlay requirements keep progressively scaling down and consequently require system improvements in immersion scanners. The on-product-overlay requirements are approaching levels of only a few nanometers, imposing stringent requirements on the scanner tool design in terms of reproducibility, accuracy and stability. In this paper we report on the performance of the NXT:1980Di immersion scanner. The NXT:1980Di builds upon the NXT:1970Ci, that is widely used for 16nm, 14nm and 10nm high-volume manufacturing. We will discuss the NXT:1980Di system- and sub-system/module enhancements that drive the scanner overlay, focus and productivity performance. Overlay, imaging, focus, productivity and defectivity data will be presented for multiple tools. To further reduce the on-product overlay system performance, alignment sensor contrast improvements as well as active reticle temperature conditioning are implemented on the NXT:1980Di. Reticle temperature conditioning will reduce reticle heating overlay and the higher contrast alignment sensor will improve alignment robustness for processed alignment targets. Due to an increased usage of multiple patterning techniques, an increased number of immersion exposures is required. NXT:1980Di scanner design modifications raised productivity levels from 250wph to 275wph. This productivity enhancement provides lower cost of ownership (CoO) for customers using immersion technology.

  6. Studying distributed cognition of simulation-based team training with DiCoT.

    PubMed

    Rybing, Jonas; Nilsson, Heléne; Jonson, Carl-Oscar; Bang, Magnus

    2016-03-01

    Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology's usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System® simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System®. We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design. PMID:26275026

  7. Temperature affects c-di-GMP signalling and biofilm formation in Vibrio cholerae.

    PubMed

    Townsley, Loni; Yildiz, Fitnat H

    2015-11-01

    Biofilm formation is crucial to the environmental survival and transmission of Vibrio cholerae, the facultative human pathogen responsible for the disease cholera. During its infectious cycle, V. cholerae experiences fluctuations in temperature within the aquatic environment and during the transition between human host and aquatic reservoirs. In this study, we report that biofilm formation is induced at low temperatures through increased levels of the signalling molecule, cyclic diguanylate (c-di-GMP). Strains harbouring in frame deletions of all V. cholerae genes that are predicted to encode diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) were screened for their involvement in low-temperature-induced biofilm formation and Vibrio polysaccharide gene expression. Of the 52 mutants tested, deletions of six DGCs and three PDEs were found to affect these phenotypes at low temperatures. Unlike wild type, a strain lacking all six DGCs did not exhibit a low-temperature-dependent increase in c-di-GMP, indicating that these DGCs are required for temperature modulation of c-di-GMP levels. We also show that temperature modulates c-di-GMP levels in a similar fashion in the Gram-negative pathogen Pseudomonas aeruginosa but not in the Gram-positive pathogen Listeria monocytogenes. This study uncovers the role of temperature in environmental regulation of biofilm formation and c-di-GMP signalling.

  8. ANALYSIS OF SPIN-ORBIT MISALIGNMENT IN THE ECLIPSING BINARY DI HERCULIS

    SciTech Connect

    Philippov, Alexander A.; Rafikov, Roman R.

    2013-05-10

    The eclipsing binary DI Herculis (DI Her) is known to exhibit anomalously slow apsidal precession below the rate predicted by general relativity. Recent measurements of the Rossiter-McLaughlin effect indicate that stellar spins in DI Her are almost orthogonal to the orbital angular momentum, which explains the anomalous precession in agreement with the earlier theoretical suggestion by Shakura. However, these measurements yield only projections of the spin-orbit angles onto the sky plane, leaving the spin projection onto our line of sight unconstrained. Here we describe a method for determining the full three-dimensional spin orientation of the binary components relying on the use of the gravity-darkening effect, which is significant for the rapidly rotating stars in DI Her. Gravity darkening gives rise to a nonuniform brightness distribution over the stellar surface, the pattern of which depends on the stellar spin orientation. Using archival photometric data obtained during multiple eclipses over several decades, we are able to constrain the unknown spin angles in DI Her with this method, finding that the spin axes of both stars lie close to the plane of the sky. Our procedure fully accounts for the precession of stellar spins over the long time span of observations.

  9. The c-di-GMP phosphodiesterase BifA regulates biofilm development in Pseudomonas putida.

    PubMed

    Jiménez-Fernández, Alicia; López-Sánchez, Aroa; Calero, Patricia; Govantes, Fernando

    2015-02-01

    We previously showed the isolation of biofilmpersistent Pseudomonas putida mutants that fail to undergo biofilm dispersal upon entry in stationary phase. Two such mutants were found to bear insertions in PP0914, encoding a GGDEF/EAL domain protein with high similarity to Pseudomon asaeruginosa BifA. Here we show the phenotypic characterization of a ΔbifA mutant in P. putida KT2442.This mutant displayed increased biofilm and pellicle formation, cell aggregation in liquid medium and decreased starvation-induced biofilm dispersal relative to the wild type. Unlike its P. aeruginosa counterpart, P. putida BifA did not affect swarming motility. The hyperadherent phenotype of the ΔbifA mutant correlates with a general increase in cyclic diguanylate (c-di-GMP) levels, Congo Red-binding exopolyaccharide production and transcription of the adhesin-encoding lapA gene. Integrity of the EAL motif and a modified GGDEF motif (altered to GGDQF)were crucial for BifA activity, and c-di-GMP depletion by overexpression of a heterologous c-di-GMP phosphodiesterase in the ΔbifA mutant restored wild-type biofilm dispersal and lapA expression.Our results indicate that BifA is a phosphodiesterase involved in the regulation of the c-di-GMP pool and required for the generation of the low c-di-GMP signal that triggers starvation-induced biofilm dispersal.

  10. Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING.

    PubMed

    Kobayashi, Hiroshi; Kobayashi, Chiharu I; Nakamura-Ishizu, Ayako; Karigane, Daiki; Haeno, Hiroshi; Yamamoto, Kimiyo N; Sato, Taku; Ohteki, Toshiaki; Hayakawa, Yoshihiro; Barber, Glen N; Kurokawa, Mineo; Suda, Toshio; Takubo, Keiyo

    2015-04-01

    Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs) migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns reportedly mediate HSPC activation, how HSPCs detect pathogen invasion in vivo remains elusive. Bacteria use the second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) for a variety of activities. Here, we report that c-di-GMP comprehensively regulated both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs while decreasing the number and repopulation capacity of long-term hematopoietic stem cells. Furthermore, we show that type I interferon acted as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while transforming growth factor-β was required for c-di-GMP-dependent splenic HSPC expansion. Our results define machinery underlying the dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling.

  11. Di-(2-ethylhexyl) phthalate and autism spectrum disorders

    PubMed Central

    Testa, Chiara; Nuti, Francesca; Hayek, Joussef; De Felice, Claudio; Chelli, Mario; Rovero, Paolo; Latini, Giuseppe; Papini, Anna Maria

    2012-01-01

    ASDs (autism spectrum disorders) are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors) suspected to interfere with neurodevelopment. Therefore they represent interesting candidate risk factors for ASD pathogenesis. The aim of this study was to evaluate the levels of the primary and secondary metabolites of DEHP [di-(2-ethylhexyl) phthalate] in children with ASD. A total of 48 children with ASD (male: 36, female: 12; mean age: 11±5 years) and age- and sex-comparable 45 HCs (healthy controls; male: 25, female: 20; mean age: 12±5 years) were enrolled. A diagnostic methodology, based on the determination of urinary concentrations of DEHP metabolites by HPLC-ESI-MS (HPLC electrospray ionization MS), was applied to urine spot samples. MEHP [mono-(2-ethylhexenyl) 1,2-benzenedicarboxylate], 6-OH-MEHP [mono-(2-ethyl-6-hydroxyhexyl) 1,2-benzenedicarboxylate], 5-OH-MEHP [mono-(2-ethyl-5-hydroxyhexyl) 1,2-benzenedicarboxylate] and 5-oxo-MEHP [mono-(2-ethyl-5-oxohexyl) 1,2-benzenedicarboxylate] were measured and compared with unequivocally characterized, pure synthetic compounds (>98%) taken as standard. In ASD patients, significant increase in 5-OH-MEHP (52.1%, median 0.18) and 5-oxo-MEHP (46.0%, median 0.096) urinary concentrations were detected, with a significant positive correlation between 5-OH-MEHP and 5-oxo-MEHP (rs = 0.668, P<0.0001). The fully oxidized form 5-oxo-MEHP showed 91.1% specificity in identifying patients with ASDs. Our findings demonstrate for the first time an association between phthalates exposure and ASDs, thus suggesting a previously unrecognized role for these

  12. Federico di Montefeltro's hyperkyphosis: a visual-historical case report

    PubMed Central

    D'Antoni, Anthony V; Terzulli, Stephanie L

    2008-01-01

    Introduction The literature contains several publications describing the use of visual arts to develop observational skills in medical students. Portraits of individuals of the Italian Renaissance can be used to enhance these skills and stimulate the development of differential diagnoses in medical students. The Duke of Urbino, Federico di Montefeltro (1422–1482), lost his right eye and nasal bridge during a jousting accident in 1450. Consequently, almost every profile of him in existence today depicts his face in a left lateral view. Although some authors have described the Duke's missing nasal bridge, none have described his prominent thoracic hyperkyphosis, which is clearly discernible in two paintings by Piero della Francesca. The purpose of this report is to describe the Duke's hyperkyphosis, develop relevant differential diagnoses, and suggest a possible etiology of the convexity. Case presentation We have examined two paintings of the Duke by Piero della Francesca – the diptych, The Duke and Duchess of Urbino (1465), and the Madonna of the Egg (1472). A MEDLINE search revealed 2 articles that were relevant to this study. This search was complemented by a search of the collection at the library of Seton Hall University, and the first author's experience studying at the University of Urbino. The historical data obtained from these searches were incorporated with the visual analysis to formulate a plausible etiology of the Duke's thoracic hyperkyphosis. Conclusion Differential diagnoses of the Duke's thoracic hyperkyphosis include Scheuermann disease, osteoporosis, and trauma-related spinal changes. Based on the available evidence, the Duke's thoracic hyperkyphosis could have been caused by repetitive trauma to the spine due to numerous hours on horseback with heavy armor. The role that osteoporosis played in the development of the hyperkyphosis is unclear, as is whether the Duke had the convexity during childhood. The hyperkyphosis as a stylistic variant

  13. Measurement of undisturbed di-nitrogen emissions from aquatic ecosystems

    NASA Astrophysics Data System (ADS)

    Qin, Shuping, Clough, Timothy, Lou, Jiafa; Hu, Chunsheng; Oenema, Oene; Wrage-Mönnig, Nicole; Zhang, Yuming

    2016-04-01

    Increased production of reactive nitrogen (Nr) from atmospheric di-nitrogen (N2) during the last century has greatly contributed to increased food production1-4. However, enriching the biosphere with Nr through N fertilizer production, combustion, and biological N2 fixation has also caused a series of negative effects on global ecosystems 5,6, especially aquatic ecosystems7. The main pathway converting Nr back into the atmospheric N2 pool is the last step of the denitrification process, i.e., the reduction of nitrous oxide (N2O) into N2 by micro-organisms7,8. Despite several attempts9,10, there is not yet an accurate, fast and direct method for measuring undisturbed N2 fluxes from denitrification in aquatic sediments at the field scale11-14. Such a method is essential to study the feedback of aquatic ecosystems to Nr inputs1,2,7. Here we show that the measurement of both N2O emission and its isotope signature can be used to infer the undisturbed N2 fluxes from aquatic ecosystems. The microbial reduction of N2O increases the natural abundance of 15N-N2O relative to 14N-N2O (δ15N-N2O). We observed linear relationships between δ15N-N2O and the logarithmic transformed N2O/(N2+N2O) emission ratios. Through independent measurements, we verified that the undisturbed N2 flux from aquatic ecosystems can be inferred from measurements of N2O emissions and the δ15N-N2O signature. Our method allows the determination of field-scale N2 fluxes from undisturbed aquatic ecosystems, and thereby allows model predictions of denitrification rates to be tested. The undisturbed N2 fluxes observed are almost one order of magnitude higher than those estimated by the traditional method, where perturbation of the system occurs, indicating that the ability of aquatic ecosystems to remove Nr may have been severely underestimated.

  14. Risk assessment of di(2-ethylhexyl) phthalate in the workplace

    PubMed Central

    2016-01-01

    Objectives A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. Methods Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. Results In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m3, as compared to the threshold exposure level of 5 mg/m3. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. Conclusions DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the

  15. Suspected acute hemolytic transfusion reaction mediated by anti-Di(a).

    PubMed

    Bennett, Ashwini; Boyapati, Ray K; Hong, Frank S

    2015-01-01

    Anti-Di(a) can mediate hemolytic disease of the fetus and newborn, but it is unclear if it can cause hemolytic transfusion reactions (HTRs). To date, there has only been one report of a possible immediate HTR attributed to anti-Di(a). Our case report details an immediate HTR due to anti-Di(a) in a patient with pre-existing liver failure. This reaction triggered multi-organ failure, and the patient subsequently died. This case also highlights the importance of considering HTRs even when routine antibody screening has been unremarkable, particularly when electronic crossmatch is used, because of the potential for an alloantibody against a low-prevalence antigen. PMID:27187197

  16. Supramolecular Hydrogels from Self-Assembly of di-Fmoc-L-lysine

    NASA Astrophysics Data System (ADS)

    Hashemnejad, Seyed Meysam; Naas, Kinsey; Kundu, Santanu

    Mechanical properties and nanostructure of a supramolecular hydrogel formed by self-assembly of di-fluorenylmethyloxycarbonyl-lysine (di-Fmoc-L-lysine) are reported here. Hydrogels were prepared by solvent switch technique in which water was added to a solution of di-Fmoc-L-lysine in dimethyl sulfoxide (DMSO). Mechanical properties of the gels were investigated using shear and cavitation rheology. The gels display strain-softening behavior at moderate strain values. Morphological investigations of the samples were conducted using FTIR and CD spectroscopy, electron microscopy, and atomic force microscopy (AFM). Self-assembled fibers with lateral dimensions ranging from 10 to 50 nm were captured in microscopy studies. FTIR results indicate β-sheet-like conformation of the peptides in the hydrogel.

  17. Cyclic (di)nucleotides: the common language shared by microbe and host.

    PubMed

    Gao, Juyi; Tao, Jianli; Liang, Weili; Jiang, Zhengfan

    2016-04-01

    Fluency in a common language allows individuals to convey information and carry out complex activities that otherwise would be difficult or even impossible without the benefit of shared communication. Cyclic (di)nucleotides have recently been recognized as such an accessible language understood by both microbe and the host, ever since remarkable progresses have revealed the molecular details of these nucleotide second messengers used in cellular communication systems. Though undergoing separate evolutionary pathways in prokaryotes and eukaryotes, cyclic (di)nucleotides enable microbes to influence host cells immediately and fiercely by modulating a variety of cellular activities. Here we highlight recent insights in cyclic (di)nucleotides and focus on the balancing of these indispensable signaling molecules by synthases and phosphodiesterases.

  18. First results with Mercedes-Benz DI diesel engines running on monoesters of vegetable oils

    SciTech Connect

    Ventura, L.M.; Nascimento, A.C.; Bandel, W.

    1982-01-01

    In their pure form the vegetable oils are not suitable for the use in modern DI diesel engines, due to the excessive carbon deposit on the injection nozzles and in the combustion chamber. Nevertheless, these oils are promising candidates as raw materials for alternative diesel fuels. Processes are being developed to transform the long vegetable oil molecules into smaller molecules in order to fulfill the fuel requirements of DI diesel engines. Methyl and ethyl esters of fatty acids e.g. obtained by transesterification of vegetable oils through their catalytic reaction with methanol and ethanol, have shown a typical diesel fuel behaviour in conventional DI engines without excessive deposit formation. Problems concerning lubricating oil contamiation, and possibile remedial measures to avoid it, are being examined. There are also problems to be solved in relation to white smoke formation and the odor of exhaust gases. 10 figures.

  19. Thyratron characteristics under high di/dt and high-repetition-rate operation

    SciTech Connect

    Ball, D.; Hill, J.; Kan, T.

    1981-05-11

    Power conditioning systems for high peak and average power, high repetition rate discharge excited lasers involve operation of modulator components in unconventional regimes. Reliable operation of switches and energy storage elements under high voltage and high di/dt conditions is a pacing item for laser development at the present time. To test and evaluate these components a Modulator Component Test Facility (MCTF) was constructed. The MCTF consists of a command charge system, energy storage capacitors, thyratron switch with inverse thyratron protection, and a resistive load. The modulator has initially been operated at voltages up to 60 kV at 600 Hz. Voltage, current, and calorimetric diagnostics are provided for major modulator components. Measurements of thyratron characteristics under high di/dt operation are presented. Commutation energy loss and di/dt have been measured as functions of the tube hydrogen pressure.

  20. Hooked on the nicotine addiction thesis: a response to DiFranza.

    PubMed

    Dar, Reuven; Frenk, Hanan

    2013-11-18

    DiFranza's rebuttal to our critique of the "Hooked on Nicotine" research program misconstrues our arguments beyond recognition. The grossest misrepresentation of our critique by DiFranza is that we devise (by thwarting science) to rescue "the conventional wisdom" of the "threshold model of nicotine addiction." In fact, the difference between our positions lies elsewhere: We believe that nicotine is not an addictive drug and that its contribution to the smoking habit is secondary; DiFranza believes that nicotine is so powerfully addictive that novice smokers can lose autonomy over their smoking behavior after one cigarette or even following a single puff. Our review aimed to critically examine the empirical basis of this extreme version of the nicotine "addiction" model. In this brief commentary we illustrate how the commitment to the nicotine "addiction" theory has biased the methodology and the interpretation of the data in "Hooked on Nicotine" research program.

  1. Di-neutrons in neutron matter within a Brueckner-Hartree-Fock approach

    NASA Astrophysics Data System (ADS)

    Isaule, Felipe; Arellano, H. F.; Rios, Arnau

    2016-09-01

    We investigate the appearance of di-neutron bound states in pure neutron matter within the Brueckner-Hartree-Fock approach at zero temperature. We consider the Argonne v18 and Paris bare interactions as well as chiral two- and three-nucleon forces. Self-consistent single-particle potentials are calculated by controlling explicitly singularities in the g matrix associated with bound states. Di-neutrons are loosely bound, with binding energies below 1 MeV, but are unambiguously present for Fermi momenta below 1 fm-1 for all interactions. Within the same framework we are able to calculate and characterize di-neutron bound states, obtaining mean radii as high as ˜110 fm. Implications of these findings are presented and discussed.

  2. The First Case Report in Italy of Di George Syndrome Detected by Noninvasive Prenatal Testing

    PubMed Central

    Rapacchia, Giuseppina; Lapucci, Cristina; Pittalis, Maria Carla; Youssef, Aly; Farina, Antonio

    2015-01-01

    Panorama Plus (Natera), a single-nucleotide polymorphism- (SNP-) based approach that relies on the identification of maternal and fetal allele distributions, allows the detection of common aneuploidies and also incorporates a panel of 5 microdeletions including Di George syndrome. We report here the first case of Di George syndrome detected by NIPT in Italy; blood was drawn at 12 weeks' gestation. The patient had an amniocentesis to confirm the diagnosis by MLPA (multiplex ligation-dependent probe amplification) and an ultrasound aimed to detect the features associated with the syndrome. A right aortic arch and suspect of thymus atrophy were detected, but not other severe malformations typical of the disease. The patient terminated the pregnancy at 17 weeks. NIPT allowed an early screening of Di George syndrome. As the patient was at low risk, it is likely that an ultrasound would have missed the condition. PMID:26346617

  3. Cyclic-di-GMP signaling in the Gram-positive pathogen Clostridium difficile.

    PubMed

    Bordeleau, Eric; Burrus, Vincent

    2015-11-01

    The anaerobic Gram-positive bacterium Clostridium difficile causes intestinal infections responsible for symptoms ranging from mild diarrhea to fulminant colitis. Like other bacteria, C. difficile needs to sense and integrate environmental signals in order to adapt to changes and thrive in its environment. The second messenger cyclic diguanosine monophosphate (c-di-GMP) was recently recognized as a quasi-ubiquitous phenotype coordinator in bacteria. Mostly known to be involved in the transition from motile to sessile and multicellular behaviors in Gammaproteobacteria, c-di-GMP is now known to regulate many other phenotypes from cell morphogenesis to virulence, in many Gram-negative and a few Gram-positive bacteria. Herein, we review recent advances in our understanding of c-di-GMP signaling in the lifecycle of C. difficile.

  4. Agar hydrogel with silver nanoparticles to prolong the shelf life of Fior di Latte cheese.

    PubMed

    Incoronato, A L; Conte, A; Buonocore, G G; Del Nobile, M A

    2011-04-01

    The objective of this work was to evaluate the effectiveness of an antimicrobial packaging system containing active nanoparticles on the quality deterioration of Fior di Latte cheese. To this aim, 3 concentrations of silver montmorillonite embedded in agar were used. The cell loads of spoilage and useful microorganisms were monitored during a refrigerated storage period. Moreover, cheese sensory quality (i.e., odor, color, consistency, and overall quality) was evaluated by means of a panel test. Results showed that the active packaging system markedly increased the shelf life of Fior di Latte cheese, due to the ability of silver cations to control microbial proliferation, without affecting the functional dairy microbiota and the sensory characteristics of the product. The active packaging system developed in this work could be used to prolong the shelf life of Fior di Latte and boost its distribution beyond local market borders.

  5. Propulsion Diagnostic Method Evaluation Strategy (ProDiMES) User's Guide

    NASA Technical Reports Server (NTRS)

    Simon, Donald L.

    2010-01-01

    This report is a User's Guide for the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES). ProDiMES is a standard benchmarking problem and a set of evaluation metrics to enable the comparison of candidate aircraft engine gas path diagnostic methods. This Matlab (The Mathworks, Inc.) based software tool enables users to independently develop and evaluate diagnostic methods. Additionally, a set of blind test case data is also distributed as part of the software. This will enable the side-by-side comparison of diagnostic approaches developed by multiple users. The Users Guide describes the various components of ProDiMES, and provides instructions for the installation and operation of the tool.

  6. c-di-GMP signalling and the regulation of developmental transitions in streptomycetes.

    PubMed

    Bush, Matthew J; Tschowri, Natalia; Schlimpert, Susan; Flärdh, Klas; Buttner, Mark J

    2015-12-01

    The complex life cycle of streptomycetes involves two distinct filamentous cell forms: the growing (or vegetative) hyphae and the reproductive (or aerial) hyphae, which differentiate into long chains of spores. Until recently, little was known about the signalling pathways that regulate the developmental transitions leading to sporulation. In this Review, we discuss important new insights into these pathways that have led to the emergence of a coherent regulatory network, focusing on the erection of aerial hyphae and the synchronous cell division event that produces dozens of unigenomic spores. In particular, we highlight the role of cyclic di-GMP (c-di-GMP) in controlling the initiation of development, and the role of the master regulator BldD in mediating c-di-GMP signalling.

  7. Quasi-two-dimensional metallic hydrogen inside di-phosphide at high pressure

    NASA Astrophysics Data System (ADS)

    Degtyarenko, N. N.; Mazur, E. A.

    2016-09-01

    The method of mathematical modelling was used for the calculation of the structural, electronic, phononic, and other characteristics of various normal phases of phosphorus hydrides with stoichiometry PHk. It was shown that the di-phosphine may form 2D lattice of the metallic hydrogen in it, stabilized by phosphorus atoms under high hydrostatic pressure. The resulting structure with the elements of H-P-H has a locally stable (or metastable) phonon spectrum. The properties of di-phosphine were compared with the properties of similar structures such as the sulphur hydrides.

  8. Synthesis, conformational and theoretical studies of 1,n-di(2-formyl-4-phenylazophenoxy)alkanes

    NASA Astrophysics Data System (ADS)

    Balachander, R.; Manimekalai, A.

    2016-01-01

    1,n-di(2-Formyl-4-phenylazophenoxy)alkanes 1 and 2 and 1,3-di(2-formyl-4-phenylazophenoxymethyl)benzene 3 were synthesis and characterized by FT-IR, UV-Vis, 1H, 13C NMR and mass spectral studies. The stable conformations of 1-3 were predicted theoretically and selected geometrical parameters were derived from optimized structures. The molecular parameters of HOMO-LUMO energies, polarizability, hyperpolarizability, natural bond orbital (NBO), atom in molecule (AIM) analysis and molecular electrostatic potential (MEP) surfaces were determined by the density functional theory (DFT) method and analysed.

  9. Stepwise aggregation of dimethyl-di-n-octylammonium chloride in aqueous solutions: from dimers to vesicles.

    PubMed

    Leclercq, Loïc; Nardello-Rataj, Véronique; Turmine, Mireille; Azaroual, Nathalie; Aubry, Jean-Marie

    2010-02-01

    The self-aggregation of dimethyl-di-n-octylammonium chloride, in diluted aqueous solutions, was studied with various experimental and theoretical techniques: zetametry, conductimetry, dimethyl-di-n-octylammonium and chloride-selective electrodes, tensiometry, NMR spectroscopy ((1)H and DOSY), and molecular modeling (PM3 and molecular dynamic). The combination of the data obtained by these techniques led us to propose a stepwise aggregation process with increasing concentration: dimers (0.2-10 mM), bilayers (10-30 mM), and finally vesicles (>30 mM).

  10. Superheavyweight missions SI versus DI: Ascent flight design options and recommendations

    NASA Technical Reports Server (NTRS)

    1990-01-01

    AFD has completed the trade study on Standard Insertion (SI) vs Direct Insertion (DI) for STS-50. RSOC Range Safety has developed acceptable DI targets from 130 n.mi. to 150 n.mi. and the corresponding performance assessment for these targets using STS-50 data has been completed. This mission has sufficient performance capability to perform this mission as a DI to 160 n.mi. A reduced OMS load corresponding to a DI mission is required for this option. The increase in altitude over the AFP baseline (SI to 145 n.mi.) is highly desirable for this mission. The orientation on orbit for the orbiter/USML-1 payload is such that orbital decay is maximized (maximum frontal cross-sectional area with vehicle normal to velocity vector). Increasing the operational altitude reduces the amount of vernier thruster firings necessary to maintain a constant gravity gradient. The results of this trade study can also be applied to other superheavyweight missions (EDO flights) and will allow for use of the DI technique for lower orbital altitudes, thereby eliminating the SI option for due east, low altitude missions. STSOC transmittal form no. 330-330-130, which documents the technical issues and assumptions used for this trade study effort in detail, should be referenced for further information. The main reason that a DI is desired for STS-50 and other superheavyweight flights (low altitude) is that ESMC range safety has expressed reservations about SI missions in general. The concern is that the current SI design underspeed exposes Africa and Madagascar to potential ET debris impact. In the past range safety has waived the requirement that these areas be protected in the event of an engine failure. With the advent of the pre-MECO OMS dump, the viability of DI and the high casualty expectations from the ACTA press to MECO hazard study, range safety has become more reluctant to approve SI flights. It is felt that to perform an SI mission there would have to be a large decrease in design

  11. [Determination of decomposition products of di-t-butyl peroxide by gas chromatography].

    PubMed

    Zhou, H; Liu, J; Wang, Y; Wu, Y

    1997-07-01

    In this work we found that there were five decomposition products of di-t-butyl peroxide at 320 degrees C by GC-MS. The peak area of acetone as a chief product in the thermal decomposition was related to di-t-butyl peroxide concentration in a linear manner. The range was from 22.91 to 114.93 microg (r=0.9997, n=4). By use of the calibration, we can possibly determine the content of the peroxide rapidly. The present method is more suitable for the determination of peroxide that is liable to decompose and difficult to be vaporized.

  12. Crystal structure of tris­(di­methyl­amido-κN)­bis­(di­methyl­amine-κN)­zirconium(IV) iodide

    PubMed Central

    Clark, Wesley D.; Akurathi, Gopalakrishna; Valle, Henry U.; Hollis, T. Keith

    2016-01-01

    Zirconium amides have become increasingly popular and useful due to their widespread use as precursors to other zirconium complexes and their use in the production of solid oxide fuel cells (SOFCs). Herein we report the mol­ecular structure of tris­(di­methyl­amido)­bis­(di­methyl­amine)­zirconium(IV) iodide, [Zr(C2H6N)3(C2H7N)2]I. The bond lengths and bond angles are consistent with a slightly distorted trigonal–bipyramidal coordination geometry around the metal atom. N⋯I contacts of 3.6153 (15) and 3.5922 (14) Å are consistent with the presence of N—H⋯I inter­actions. These N—H⋯I inter­actions link the complex cations and iodide anions into extended chains that propagate parallel to the a axis. PMID:26870590

  13. catena-Poly[[[tetra-aqua-magnesium]-trans-μ-[(piperazine-1,4-diium-1,4-di-yl)bis-(methyl-ene)]di-phospho-nato] hemihydrate].

    PubMed

    Schilling, Lars-Hendrik; Stock, Norbert

    2013-01-01

    The structure of the title polymer, }[Mg(C6H14N2O6P2)(H2O)4]·0.5H2O} n , is based on centrosymmetric MgO6 octahedra, which are linked by [(piperazine-1,4-diium-1,4-di-yl)bis-(methyl-ene)]di-phospho-nate ligands, forming chains parallel to [1-1-1]. These chains are connected via hydrogen bonds primarily formed between the phospho-nate groups and water mol-ecules. The latter constitute four of the corners of the MgO6 polyhedra and bind to the O atoms of the phospho-nate groups of neighbouring chains. The lattice water molecule is disordered around an inversion centre, exhibiting an occupancy of 0.25. PMID:24109276

  14. (Di­methyl­phosphor­yl)methanaminium iodide–(di­methyl­phosphor­yl)methan­amine (1/1)

    PubMed Central

    Reiss, Guido J.

    2013-01-01

    The asymmetric unit of the title structure, C3H11NOP+·I−·C3H10NOP, consists of one (di­methyl­phosphor­yl)methanamine (dpma) mol­ecule, one (di­methyl­phosphor­yl)methanaminium (dpmaH) ion and one iodide counter-anion. In the crystal, medium–strong to weak N—H⋯O and N—H⋯N hydrogen bonds connect dpmaH cations and dpma mol­ecules into strands along [001]. The iodide counter-anions form only very weak hydrogen bonds. The crystal used for the diffraction study was found to be an inversion twin with a ratio of 0.83 (2):0.17 (2). The title structure is isotypic to that of dpmaH[ClO4]·dpma [Buhl et al. (2013 ▶). Crystals 3, 350–362]. PMID:24109340

  15. Diethyl 4-(biphenyl-4-yl)-2,6-dimethyl-1,4-di­hydro­pyridine-3,5-di­carboxyl­ate

    PubMed Central

    Steiger, Scott A.; Monacelli, Anthony J.; Li, Chun; Hunting, Janet L.; Natale, Nicholas R.

    2014-01-01

    The title compound, C25H27NO4, has a flattened di­hydro­pyridine ring. The benzene and phenyl rings are synclinal to one another, forming a dihedral angle of 49.82 (8)°; the axis of the biphenyl rings makes an 81.05 (9)° angle to the plane of the di­hydro­pyridine ring. In the crystal, N—H⋯O hydrogen bonds link the mol­ecules into chain motifs running along the a-axis direction. The chains are cross-linked by C—H⋯O inter­actions, forming sheet motifs running slightly off the (110) plane, together with an intermolecular interaction between head-to tail biphenyl groups, thus making the whole crystal packing a three-dimensional network. Intra­molecular C—H⋯O hydrogen bonds are also observed. PMID:25161575

  16. [Valutare le esperienze positive e negative: la validazione di una nuova misura del benessere in una popolazione italiana].

    PubMed

    Corno, Giulia; Molinari, Guadalupe; Baños, Rosa Maria

    2016-01-01

    RIASSUNTO. Lo scopo del presente studio è quello di esplorare le proprietà psicometriche di uno strumento di misurazione dell'affetto, la Scala di Esperienze Positive e Negative (SPANE), all'interno di una popolazione italiana. Gli esiti dell'analisi fattoriale confermativa comprovano l'attesa struttura a due fattori, sentimenti positivi e negativi. Le correlazioni con altre dimensioni (per es., ansia, depressione, affetto, aspettative future) confermano i risultati ottenuti con le precedenti versioni della scala: affetto negativo, ansia, depressione e aspettative future negative correlano positivamente con la subscala di esperienze negative e negativamente con la subscala di esperienze positive dello SPANE. In conclusione, i risultati del nostro studio dimostrano che la versione italiana dello SPANE presenta caratteristiche psicometriche simili a quelle mostrate dalla versione orginale e da successive validazioni dello strumento in altre lingue. La scala presenta, inoltre, affidabilità e validità fattoriale. Lo SPANE è un indice utile dal punto di vista clinico che può fornire informazioni rilevanti circa l'esperienza emotiva e il benessere della persona. Nonostante ulteriori studi siano necessari per confermare le caratteristiche psicometriche della scala, la presente validazione della versione italiana dello SPANE può contribuire ad ampliare la ricerca nell'ambito del benessere in una popolazione Italiana. PMID:27362822

  17. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development (HUD). 644.336 Section 644.336... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban...

  18. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development... of Education property suitable for educational purposes or to protect the public health, and to HUD... 32 National Defense 4 2014-07-01 2013-07-01 true Notices to Departments of Interior (DI);...

  19. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development... of Education property suitable for educational purposes or to protect the public health, and to HUD... 32 National Defense 4 2013-07-01 2013-07-01 false Notices to Departments of Interior (DI);...

  20. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development... of Education property suitable for educational purposes or to protect the public health, and to HUD... 32 National Defense 4 2012-07-01 2011-07-01 true Notices to Departments of Interior (DI);...

  1. PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

    The plasticizer Di (2-ethylhexyl) phtha...

  2. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development (HUD). 644.336 Section 644.336... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban...

  3. [Valutare le esperienze positive e negative: la validazione di una nuova misura del benessere in una popolazione italiana].

    PubMed

    Corno, Giulia; Molinari, Guadalupe; Baños, Rosa Maria

    2016-01-01

    RIASSUNTO. Lo scopo del presente studio è quello di esplorare le proprietà psicometriche di uno strumento di misurazione dell'affetto, la Scala di Esperienze Positive e Negative (SPANE), all'interno di una popolazione italiana. Gli esiti dell'analisi fattoriale confermativa comprovano l'attesa struttura a due fattori, sentimenti positivi e negativi. Le correlazioni con altre dimensioni (per es., ansia, depressione, affetto, aspettative future) confermano i risultati ottenuti con le precedenti versioni della scala: affetto negativo, ansia, depressione e aspettative future negative correlano positivamente con la subscala di esperienze negative e negativamente con la subscala di esperienze positive dello SPANE. In conclusione, i risultati del nostro studio dimostrano che la versione italiana dello SPANE presenta caratteristiche psicometriche simili a quelle mostrate dalla versione orginale e da successive validazioni dello strumento in altre lingue. La scala presenta, inoltre, affidabilità e validità fattoriale. Lo SPANE è un indice utile dal punto di vista clinico che può fornire informazioni rilevanti circa l'esperienza emotiva e il benessere della persona. Nonostante ulteriori studi siano necessari per confermare le caratteristiche psicometriche della scala, la presente validazione della versione italiana dello SPANE può contribuire ad ampliare la ricerca nell'ambito del benessere in una popolazione Italiana.

  4. 40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... vinyl, hydroxy-terminated, reaction products with -modified silica. 721.10483 Section 721.10483... Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with -modified silica. (a... Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with -modified silica (PMN...

  5. 40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... vinyl, hydroxy-terminated, reaction products with silica. 721.10482 Section 721.10482 Protection of... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and..., di-Me, Me vinyl, hydroxy-terminated, reaction products with silica (PMN P-04-430; CAS No....

  6. 40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... vinyl, hydroxy-terminated, reaction products with -modified silica. 721.10483 Section 721.10483... Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with -modified silica. (a... Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with -modified silica (PMN...

  7. 40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... vinyl, hydroxy-terminated, reaction products with silica. 721.10482 Section 721.10482 Protection of... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and..., di-Me, Me vinyl, hydroxy-terminated, reaction products with silica (PMN P-04-430; CAS No....

  8. Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5

    ERIC Educational Resources Information Center

    Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C.; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin

    2016-01-01

    The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical…

  9. Morphology Control of Cadmium Selenide Nanocrystals: Insights into the Roles of Di-n-octylphosphine Oxide (DOPO) and Di-n-octylphosphinic Acid (DOPA)

    PubMed Central

    2012-01-01

    Di-n-octylphosphine oxide (DOPO) and di-n-octylphosphinic acid (DOPA), as two of impurities found in commercial tri-n-octylphosphine oxide (TOPO), generate significant differences in the outcomes of CdSe-nanocrystal (NC) syntheses. Using n-tetradecylphosphonic acid (TDPA) as the primary acid additive, quantum dots (QDs) are grown with DOPO added, whereas quantum rods (QRs) are grown in the presence of DOPA. While using oleic acid (OA) as the primary acid additive, QDs are generated and the QDs produced with DOPA exhibit larger sizes and size distributions than those produced with DOPO. 31P NMR analyses of the reaction mixtures reveal that the majority of the DOPO has been converted into DOPA and di-n-octylphosphine (DOP) with DOP being removed via evacuation over the course of Cd-precursor preparation. The origin of the puzzling differences in the shape control of CdSe NCs in the presence of DOPO and DOPA is elucidated to be the small quantity of DOPO present, which liberates DOP during NC synthesis. In the presence of DOP, regardless of DOPA, the precursor-conversion kinetics and thus the nucleation kinetics are dramatically accelerated, generating a large number of nuclei by consuming a significant amount of CdSe nutrients, favoring QD growth. Similarly, QD growth is favored by the fast nucleation kinetics in the presence of OA, and the broader size distributions of QDs with DOPA are due to a second nucleation event initiated by the more stable Cd-di-n-octylphosphinate component. In contrast, a slow nucleation event results in the growth of QRs in the case of using DOPA and TDPA, where no DOPO or DOP is present. The results thus demonstrate the important role of precursor-conversion kinetics in the control of NC morphologies. PMID:22369500

  10. Di- and triphenylacetate complexes of yttrium and europium.

    PubMed

    Minyaev, Mikhail E; Vinogradov, Alexandr A; Roitershtein, Dmitrii M; Lyssenko, Konstantin A; Ananyev, Ivan V; Nifant'ev, Ilya E

    2016-07-01

    The significant variety in the crystal structures of rare-earth carboxylate complexes is due to both the large coordination numbers of the rare-earth cations and the ability of the carboxylate anions to form several types of bridges between rare-earth metal atoms. Therefore, these complexes are represented by mono-, di- and polynuclear complexes, and by coordination polymers. The interaction of LnCl3(thf)x (Ln = Eu or Y; thf is tetrahydrofuran) with sodium or diethylammonium diphenylacetate in methanol followed by recrystallization from a DME/THF/hexane solvent mixture (DME is 1,2-dimethoxyethane) leads to crystals of the non-isomorphic dinuclear complexes tetrakis(μ-2,2-diphenylacetato)-κ(4)O:O';κ(3)O,O':O';κ(3)O:O,O'-bis[(1,2-dimethoxyethane-κ(2)O,O')(2,2-diphenylacetato-κ(2)O,O')europium(III)], [Eu(C14H11O2)6(C4H10O2)2], (I), and tetrakis(μ-2,2-diphenylacetato)-κ(4)O:O';κ(3)O,O':O';κ(3)O:O,O'-bis[(1,2-dimethoxyethane-κ(2)O,O')(2,2-diphenylacetato-κ(2)O,O')yttrium(III)], [Y(C14H11O2)6(C4H10O2)2], (II), possessing monoclinic (P21/c) symmetry. The [Ln(Ph2CHCOO)3(dme)]2 molecule (Ln = Eu or Y) lies on an inversion centre and exhibits three different coordination modes of the diphenylacetate ligands, namely bidentate κ(2)O,O'-terminal, bidentate μ2-κ(1)O:κ(1)O'-bridging and tridentate μ2-κ(1)O:κ(2)O,O'-semibridging. The terminal and bridging ligands in (I) are disordered over two positions, with an occupancy ratio of 0.806 (2):0.194 (2). The interaction of EuCl3(thf)2 with Na[Ph3CCOO] in methanol followed by crystallization from hot methanol produces crystals of tetrakis(methanol-κO)tris(2,2,2-triphenylacetato)-κ(4)O:O';κO-europium(III) methanol disolvate, [Eu(C19H15O2)3(CH3OH)4]·2CH3OH, (III)·2MeOH, with triclinic (P-1) symmetry. The molecule of (III) contains two O,O'-bidentate and one O-monodentate terminal triphenylacetate ligand. (III)·2MeOH possesses one intramolecular and four intermolecular hydrogen bonds, forming a [(III)·2Me

  11. Regulation of biofilm formation and cellular buoyancy through modulating intracellular cyclic di-GMP levels in engineered cyanobacteria.

    PubMed

    Agostoni, Marco; Waters, Christopher M; Montgomery, Beronda L

    2016-02-01

    The second messenger cyclic dimeric (3'→5') GMP (cyclic di-GMP or c-di-GMP) has been implicated in the transition between motile and sessile lifestyles in bacteria. In this study, we demonstrate that biofilm formation, cellular aggregation or flocculation, and cellular buoyancy are under the control of c-di-GMP in Synechocystis sp. PCC 6803 (Synechocystis) and Fremyella diplosiphon. Synechocystis is a unicellular cyanobacterium and displays lower levels of c-di-GMP; F. diplosiphon is filamentous and displays higher intracellular c-di-GMP levels. We transformed Synechocystis and F. diplosiphon with a plasmid for constitutive expression of genes encoding diguanylate cylase (DGC) and phosphodiesterase (PDE) proteins from Vibrio cholerae or Escherichia coli, respectively. These engineered strains allowed us to modulate intracellular c-di-GMP levels. Biofilm formation and cellular deposition were induced in the DGC-expressing Synechocystis strain which exhibited high intracellular levels of c-di-GMP; whereas strains expressing PDE in Synechocystis and F. diplosiphon to drive low intracellular levels of c-di-GMP exhibited enhanced cellular buoyancy. In addition, the PDE-expressing F. diplosiphon strain showed elevated chlorophyll levels. These results imply roles for coordinating c-di-GMP homeostasis in regulating native cyanobacterial phenotypes. Engineering exogenous DGC or PDE proteins to regulate intracellular c-di-GMP levels represents an effective tool for uncovering cryptic phenotypes or modulating phenotypes in cyanobacteria for practical applications in biotechnology applicable in photobioreactors and in green biotechnologies, such as energy-efficient harvesting of cellular biomass or the treatment of metal-containing wastewaters.

  12. Systematic analysis of cyclic di-GMP signaling enzymes and their role in biofilm formation and virulence in Yersinia pestis

    PubMed Central

    Bobrov, Alexander G.; Kirillina, Olga; Ryjenkov, Dmitri A.; Waters, Christopher M.; Price, Paul A.; Fetherston, Jacqueline D.; Mack, Dietrich; Goldman, William E.; Gomelsky, Mark; Perry, Robert D.

    2011-01-01

    Cyclic di-GMP (c-di-GMP) is a signaling molecule that governs the transition between planktonic and biofilm states. Previously we showed that the diguanylate cyclase HmsT and the putative c-di-GMP phosphodiesterase HmsP inversely regulate biofilm formation through control of HmsHFRS-dependent poly-β-1,6-N-acetylglucosamine synthesis. Here, we systematically examine the functionality of the genes encoding putative c-di-GMP metabolic enzymes in Yersinia pestis. We determine that, in addition to hmsT and hmsP, only the gene y3730 encodes a functional enzyme capable of synthesizing c-di-GMP. The seven remaining genes are pseudogenes or encode proteins that do not function catalytically or are not expressed. Furthermore, we show that HmsP has c-di-GMP-specific phosphodiesterase activity. We report that a mutant incapable of c-di-GMP synthesis is unaffected in virulence in plague mouse models. Conversely, an hmsP mutant, unable to degrade c-di-GMP, is defective in virulence by a subcutaneous route of infection due to poly-β-1,6-N-acetylglucosamine overproduction. This suggests that c-di-GMP signaling is not only dispensable but deleterious for Y. pestis virulence. Our results show that a key event in the evolution of Y. pestis from the ancestral Yersinia pseudotuberculosis was a significant reduction in the complexity of its c-di-GMP signaling network likely resulting from the different disease cycles of these human pathogens. PMID:21219468

  13. Bi-modal Distribution of the Second Messenger c-di-GMP Controls Cell Fate and Asymmetry during the Caulobacter Cell Cycle

    PubMed Central

    Abel, Sören; Hug, Isabelle; Kaever, Volkhard; Abel zur Wiesch, Pia; Jenal, Urs

    2013-01-01

    Many bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP. Behavioral transitions result from the coordination of complex cellular processes such as motility, surface adherence or the production of virulence factors and toxins. While the regulatory mechanisms responsible for these processes have been elucidated in some cases, the global pleiotropic effects of c-di-GMP are poorly understood, primarily because c-di-GMP networks are inherently complex in most bacteria. Moreover, the quantitative relationships between cellular c-di-GMP levels and c-di-GMP dependent phenotypes are largely unknown. Here, we dissect the c-di-GMP network of Caulobacter crescentus to establish a global and quantitative view of c-di-GMP dependent processes in this organism. A genetic approach that gradually reduced the number of diguanylate cyclases identified novel c-di-GMP dependent cellular processes and unraveled c-di-GMP as an essential component of C. crescentus cell polarity and its bimodal life cycle. By varying cellular c-di-GMP concentrations, we determined dose response curves for individual c-di-GMP-dependent processes. Relating these values to c-di-GMP levels modeled for single cells progressing through the cell cycle sets a quantitative frame for the successive activation of c-di-GMP dependent processes during the C. crescentus life cycle. By reconstructing a simplified c-di-GMP network in a strain devoid of c-di-GMP we defined the minimal requirements for the oscillation of c-di-GMP levels during the C. crescentus cell cycle. Finally, we show that although all c-di-GMP dependent cellular processes were qualitatively restored by artificially adjusting c-di-GMP levels with a heterologous diguanylate cyclase, much higher levels of the second messenger are required under these conditions as compared to the contribution of homologous c-di-GMP metabolizing enzymes. These experiments suggest that a common c-di-GMP pool cannot fully

  14. DEVELOPMENTAL EXPOSURE TO DI-N-BUTYLTIN DICHLORIDE (DBTC): IMMUNOTOXIC AND NEUROTOXIC EVALUATION

    EPA Science Inventory

    Organotins are incorporated as stabilizers in PVC water supply pipe. Particularly when new, mono- and di-substituted methyl- and butyltins leach from the pipe and are thus of regulatory concern to EPA. These contaminants have adverse effects on both the immune and nervous systems...

  15. MECHANISTIC CONSIDERATIONS FOR HUMAN RELEVANCE OF CANCER HAZARD OF DI(2-ETHYLHEXYL) PHTHALATE

    EPA Science Inventory

    Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and enviro...

  16. Genetic Modifiers of the Physical Malformations in Velo-Cardio-Facial Syndrome/DiGeorge Syndrome

    ERIC Educational Resources Information Center

    Aggarwal, Vimla S.; Morrow, Bernice E.

    2008-01-01

    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid, and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that "Tbx1", a…

  17. Dose Reconstruction of Di-2-Ethylhexyl Phthalate Using a Simple Pharmacokinetic Model [Manuscript

    EPA Science Inventory

    Background In 2005, eight adults provided full volumes and times of urine voids during one normal work week. These samples were analyzed for four di-2-ethylhexyl phthalate (DEHP) metabolites. Participants also provided diary information on their diet, driving, and out¬door a...

  18. VITELLOGENIN GENE EXPRESSION IN MALE FATHEAD MINNOWS EXPOSED TO DI(2-ETHYLHEXYL)PHTHALATE

    EPA Science Inventory

    Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used extensively in the plastics industry. DEHP has been shown to be ubiquitous in the environment and has been detected in ground and surface waters, sediment sludge and at several Superfund sites. Previous studies using rats ...

  19. Endoplasmic reticulum stress as a novel cellular response to di (2-ethylhexyl) phthalate exposure.

    PubMed

    Peropadre, Ana; Fernández Freire, Paloma; Pérez Martín, José Manuel; Herrero, Óscar; Hazen, María José

    2015-12-25

    Di (2-ethylhexyl) phthalate is a high-production chemical widely used as a plasticizer for polyvinyl chloride products. Due to its ubiquitous presence in environmental compartments and the constant exposure of the general population through ingestion, inhalation, and dermal absorption, this compound has been subjected to extensive in vivo and in vitro toxicological studies. Despite the available information, research on the cytotoxicity of di (2-ethylhexyl) phthalate in mammalian cells is relatively limited.In this paper, an in vitro multi-parametric approach was used to provide further mechanistic data on the toxic activity of this chemical in Vero and HaCaT cells. Our results reveal that a 24 h exposure to di (2-ethylhexyl) phthalate causes, in both cell lines, an inhibition of cell proliferation that was linked to cell cycle delay at the G1 phase. Concomitantly, the tested compound induces mild endoplasmic reticulum stress which leads to an adaptive rather than a pro-apoptotic response in mammalian cells. These findings demonstrate that there are multiple potential cellular targets of di (2-ethylhexyl) phthalate-induced toxicity and the need to develop further experimental studies for the risk assessment of this ubiquitous plasticizer.

  20. Comparative studies on calotropins DI and DII from the latex of Calotropis gigantea.

    PubMed

    Sengupta, A; Bhattacharya, D; Pal, G; Sinha, N K

    1984-07-01

    Autodigestion of two cysteine proteinases, calotropins DI and DII isolated from the latex of Calotropis gigantea, has been studied at pH 7.5 and 37 degrees C in the presence of an activating agent. Calotropin DI is more susceptible to autodigestion than calotropin DII. During autodigestion no interconversion of one calotropin to another has occurred, as verified by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. Immunologically, both calotropins are closely related, but they differ from papain and ficin. Both calotropins have blocked N-terminal amino acid residues. Their C-terminal amino acid sequences, determined by treatment with carboxypeptidase Y, are -(Pro, Ala)-Ala-Val-Tyr for calotropin DI and -(Ala, Val)-Ala-Pro-Tyr for calotropin DII. The tryptic peptide maps of their reduced and S-carboxymethylated derivatives suggest that both calotropins share a high proportion of common regions in their amino acid sequences. Calotropins DI and DII are two distinct proteinases, and they do not appear to be produced by autodigestion of a single precursor. Although they are inert to the common synthetic substrates of papain and ficin, their specificities toward oxidized insulin B chain are comparable to those of papain and ficin.

  1. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity.

    PubMed

    Osbourne, Devon O; Soo, Valerie W C; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease.

  2. B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly

    PubMed Central

    Ramos, J.; Lopez-Laso, E.; Ruiz-Contreras, J.; Giancaspro, E.; Madero, S.

    1999-01-01

    The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.

 PMID:10519724

  3. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes.

    PubMed

    Nowosinski, Karol; von Krbek, Larissa K S; Traulsen, Nora L; Schalley, Christoph A

    2015-10-16

    A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

  4. Production technology and characterization of Fior di latte cheeses made from sheep and goat milks.

    PubMed

    Faccia, M; Trani, A; Gambacorta, G; Loizzo, P; Cassone, A; Caponio, F

    2015-03-01

    Innovation in the small ruminant dairy sector faces structural challenges because dairies are often involved in breeding and produce cheeses that appeal essentially to local markets using traditional technologies and facilities. An investigation was carried out to produce Fior di latte, a traditional, soft pasta filata cheese, from sheep and goat milks at the farm level. Fior di latte is an Italian high-moisture, round mozzarella currently produced from cow and water buffalo milks; it is very popular in Europe. Cheesemaking trials were performed and the most appropriate technology proved to be a combination of direct acidification and lactic fermentation, with some modifications to the milk coagulation phase. The gross composition of the experimental cheeses was similar to that of bovine Fior di latte, and the overall hygienic quality was satisfactory even though the milk had not been pasteurized. The new cheeses were similar in appearance to the bovine type, but some specific features were detected. Besides the typical "goaty" and "sheepy" flavors, some novel and distinctive descriptors of odor, flavor, and texture were noted. Our experiment showed that good quality Fior di latte cheese that complies with microbiological requirements of the European legislation can be obtained from sheep and goat milks by appropriately modifying the cheesemaking technology.

  5. H.p.l.c. analysis of di- and tri-carboxylic porphyrins in porphyric patients.

    PubMed Central

    Jackson, A H; Rao, K R; Smith, S G; Lash, T D

    1985-01-01

    New h.p.l.c. methods have been developed for the quantitative determination of di- and tri-carboxylic porphyrin methyl esters, and applied to the analysis of faecal extracts from patients with four different types of porphyria. PMID:3994688

  6. Pyrosequencing with di-base addition for single nucleotide polymorphism genotyping.

    PubMed

    Pu, Dan; Mao, Chengguang; Cui, Lunbiao; Shi, Zhiyang; Xiao, Pengfeng

    2016-05-01

    We develop color code-based pyrosequencing with di-base addition for analysis of single nucleotide polymorphisms (SNPs). When a di-base is added into the polymerization, one or several two-color code(s) containing the type and the number of incorporated nucleotides will be produced. The code information obtained in a single run is useful to genotype SNPs as each allelic variant will give a specific pattern compared to the two other variants. Special care has to be taken while designing the di-base dispensation order. Here, we present a detailed protocol for establishing sequence-specific di-base addition to avoid nonsynchronous extension at the SNP sites. By using this technology, as few as 50 copies of DNA templates were accurately sequenced. Higher signals were produced and thus a relatively lower sample amount was required. Furthermore, the read length of per flow was increased, making simultaneous identification of multiple SNPs in a single sequencing run possible. Validation of the method was performed by using templates with two SNPs covering 37 bp and with three SNPs covering 58 bp as well as 82 bp. These SNPs were successfully genotyped by using only a sequencing primer in a single PCR/sequencing run. Our results demonstrated that this technology could be potentially developed into a powerful methodology to accurately determine SNPs so as to diagnose clinical settings.

  7. MODULATION OF RAT LEYDIG CELL STEROIDOGENIC FUNCTION BY DI(2-ETHYLHEXYL)PHTHALATE

    EPA Science Inventory

    Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate.

    Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, Zirkin BR, Hardy MP.

    Center for Biomedical Research, Population Council, New York, New York 10021, USA. benson@popcbr...

  8. Pyrosequencing with di-base addition for single nucleotide polymorphism genotyping.

    PubMed

    Pu, Dan; Mao, Chengguang; Cui, Lunbiao; Shi, Zhiyang; Xiao, Pengfeng

    2016-05-01

    We develop color code-based pyrosequencing with di-base addition for analysis of single nucleotide polymorphisms (SNPs). When a di-base is added into the polymerization, one or several two-color code(s) containing the type and the number of incorporated nucleotides will be produced. The code information obtained in a single run is useful to genotype SNPs as each allelic variant will give a specific pattern compared to the two other variants. Special care has to be taken while designing the di-base dispensation order. Here, we present a detailed protocol for establishing sequence-specific di-base addition to avoid nonsynchronous extension at the SNP sites. By using this technology, as few as 50 copies of DNA templates were accurately sequenced. Higher signals were produced and thus a relatively lower sample amount was required. Furthermore, the read length of per flow was increased, making simultaneous identification of multiple SNPs in a single sequencing run possible. Validation of the method was performed by using templates with two SNPs covering 37 bp and with three SNPs covering 58 bp as well as 82 bp. These SNPs were successfully genotyped by using only a sequencing primer in a single PCR/sequencing run. Our results demonstrated that this technology could be potentially developed into a powerful methodology to accurately determine SNPs so as to diagnose clinical settings. PMID:26935928

  9. Endoplasmic reticulum stress as a novel cellular response to di (2-ethylhexyl) phthalate exposure.

    PubMed

    Peropadre, Ana; Fernández Freire, Paloma; Pérez Martín, José Manuel; Herrero, Óscar; Hazen, María José

    2015-12-25

    Di (2-ethylhexyl) phthalate is a high-production chemical widely used as a plasticizer for polyvinyl chloride products. Due to its ubiquitous presence in environmental compartments and the constant exposure of the general population through ingestion, inhalation, and dermal absorption, this compound has been subjected to extensive in vivo and in vitro toxicological studies. Despite the available information, research on the cytotoxicity of di (2-ethylhexyl) phthalate in mammalian cells is relatively limited.In this paper, an in vitro multi-parametric approach was used to provide further mechanistic data on the toxic activity of this chemical in Vero and HaCaT cells. Our results reveal that a 24 h exposure to di (2-ethylhexyl) phthalate causes, in both cell lines, an inhibition of cell proliferation that was linked to cell cycle delay at the G1 phase. Concomitantly, the tested compound induces mild endoplasmic reticulum stress which leads to an adaptive rather than a pro-apoptotic response in mammalian cells. These findings demonstrate that there are multiple potential cellular targets of di (2-ethylhexyl) phthalate-induced toxicity and the need to develop further experimental studies for the risk assessment of this ubiquitous plasticizer. PMID:26514933

  10. Di(phenylpropylamino)gossypol: a derivative of the dimeric natural product gossypol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Di(phenylpropylamino)gossypol [2,2'-bis(1,6-dihydroxy,-5-isopropyl,-8-methineaminopropylbenzene-3-methyl)-naphthylene-7-one, C48H52N2O6] is formed by reaction of the dimeric natural product gossypol with 3-phenyl-1-propylamine. When crystallized from diethyl ether, the compound has monoclinic (P21/c...

  11. Synthesis and characterization of DI-[3-(trimethylsilyl)-1-propylene] alkylenediphosphonic acids.

    SciTech Connect

    Griffith-Dzielawa, J. A.; Barrans, R. E., Jr.; McAlister, D. R.; Dietz, M. L.; Herlinger, A. W.; Chemistry; Loyola Univ. of Chicago

    2000-01-01

    A homologous series of alkylenediphosphonic acids was successfully esterified with 3-(trimethylsilyl)-1-propanol to the symmetrically-substituted diesters. The procedure, which has general applicability for incorporating silicon heteroatoms into diphosphonic acids, utilizes the esterification reagent dicyclohexyl-carbodiimide (DCC) to activate the acid. The aggregation properties of the di-[3-(trimethylsilyl)-1-propylene] alkylenediphosphonic acids were measured in toluene and 1-decanol.

  12. Stabilization and detection of hydrophylloquinone as di-O-methyl derivative.

    PubMed

    Sussmann, Rodrigo A C; de Moraes, Marcilio M; Cebrián-Torrejón, Gerardo; Porta, Exequiel O; Doménech-Carbó, Antonio; Yamaguchi, Lydia F; Katzin, Alejandro M; Kato, Massuo J

    2016-10-15

    Phylloquinone is a redox active naphthoquinone involved in electron transport in plants. The function of this reduced form remains unclear due to its instability, which has precluded detection. Herein, a simple method that permits the stabilization of the reduced form of phylloquinone by di-O-methylation and HPLC detection is described.

  13. Draft Genome Sequence of the Xylella fastidiosa CoDiRO Strain.

    PubMed

    Giampetruzzi, Annalisa; Chiumenti, Michela; Saponari, Maria; Donvito, Giacinto; Italiano, Alessandro; Loconsole, Giuliana; Boscia, Donato; Cariddi, Corrado; Martelli, Giovanni Paolo; Saldarelli, Pasquale

    2015-01-01

    We determined the draft genome sequence of the Xylella fastidiosa CoDiRO strain, which has been isolated from olive plants in southern Italy (Apulia). It is associated with olive quick decline syndrome (OQDS) and characterized by extensive scorching and desiccation of leaves and twigs. PMID:25676759

  14. Draft Genome Sequence of Sphingobium yanoikuyae TJ, a Halotolerant Di-n-Butyl-Phthalate-Degrading Bacterium

    PubMed Central

    Jin, Decai; Zhu, Ying; Wang, Xinxin; Kong, Xiao; Liu, Huijun; Wang, Yafeng

    2016-01-01

    Sphingobium yanoikuyae TJ is a halotolerant di-n-butyl-phthalate-degrading bacterium, isolated from the Haihe estuary in Bohai Bay, Tianjin, China. Here, we report the 5.1-Mb draft genome sequence of this strain, which will provide insights into the diversity of Sphingobium spp. and the mechanism of phthalate ester degradation in the estuary. PMID:27313307

  15. The Theory behind the Theory in DCT and SCDT: A Response to Rigazio-DiGilio.

    ERIC Educational Resources Information Center

    Terry, Linda L.

    1994-01-01

    Responds to previous article by Rigazio-DiGilio on Developmental Counseling and Therapy and Systemic Cognitive-Developmental Therapy as two integrative models that unify individual, family, and network treatment within coconstructive-developmental framework. Discusses hidden complexities in cognitive-developmental ecosystemic integration and…

  16. The phosphatidylethanolamine derivative diDCP-LA-PE mimics intracellular insulin signaling.

    PubMed

    Nishizaki, Tomoyuki; Gotoh, Akinobu; Shimizu, Tadashi; Tanaka, Akito

    2016-06-02

    Insulin facilitates glucose uptake into cells by translocating the glucose transporter GLUT4 towards the cell surface through a pathway along an insulin receptor (IR)/IR substrate 1 (IRS-1)/phosphatidylinositol 3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis. The newly synthesized phosphatidylethanolamine derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE) has the potential to inhibit protein tyrosine phosphatase 1B (PTP1B) and to directly activate PKCζ, an atypical isozyme, and PKCε, a novel isozyme. PTP1B inhibition enhanced insulin signaling cascades downstream IR/IRS-1 by preventing tyrosine dephosphorylation. PKCζ and PKCε directly activated Akt2 by phosphorylating at Thr309 and Ser474, respectively. diDCP-LA-PE increased cell surface localization of GLUT4 and stimulated glucose uptake into differentiated 3T3-L1 adipocytes, still with knocking-down IR or in the absence of insulin. Moreover, diDCP-LA-PE effectively reduced serum glucose levels in type 1 diabetes (DM) model mice. diDCP-LA-PE, thus, may enable type 1 DM therapy without insulin injection.

  17. The phosphatidylethanolamine derivative diDCP-LA-PE mimics intracellular insulin signaling

    PubMed Central

    Nishizaki, Tomoyuki; Gotoh, Akinobu; Shimizu, Tadashi; Tanaka, Akito

    2016-01-01

    Insulin facilitates glucose uptake into cells by translocating the glucose transporter GLUT4 towards the cell surface through a pathway along an insulin receptor (IR)/IR substrate 1 (IRS-1)/phosphatidylinositol 3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis. The newly synthesized phosphatidylethanolamine derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE) has the potential to inhibit protein tyrosine phosphatase 1B (PTP1B) and to directly activate PKCζ, an atypical isozyme, and PKCε, a novel isozyme. PTP1B inhibition enhanced insulin signaling cascades downstream IR/IRS-1 by preventing tyrosine dephosphorylation. PKCζ and PKCε directly activated Akt2 by phosphorylating at Thr309 and Ser474, respectively. diDCP-LA-PE increased cell surface localization of GLUT4 and stimulated glucose uptake into differentiated 3T3-L1 adipocytes, still with knocking-down IR or in the absence of insulin. Moreover, diDCP-LA-PE effectively reduced serum glucose levels in type 1 diabetes (DM) model mice. diDCP-LA-PE, thus, may enable type 1 DM therapy without insulin injection. PMID:27251941

  18. A thermal lensing study of a photolysis of di- t-butyl peroxide

    NASA Astrophysics Data System (ADS)

    Fuke, K.; Hasegawa, A.; Ueda, M.; Itoh, M.

    1981-11-01

    A photolysis of di- t-butyl peroxide (BOOB) was studied by using a thermal lensing technique. This technique is found to be applicable to the determination Of the rate Constants of the decay of t-butoxy radical (BO ) and the hydrogen abstraction reaction.

  19. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity

    PubMed Central

    Osbourne, Devon O; Soo, Valerie WC; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease. PMID:24874800

  20. Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

    SciTech Connect

    Friedmann, P.S.; Wren, F.E.; Matthews, J.N. )

    1990-02-01

    Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C.

  1. DiMeX: A Text Mining System for Mutation-Disease Association Extraction

    PubMed Central

    Mahmood, A. S. M. Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K.

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases. PMID:27073839

  2. Gel-electrophoretic identification of hen brain neurotoxic esterase, labelled with tritiated di-isopropyl phosphorofluoridate.

    PubMed Central

    Williams, D G; Johnson, M K

    1981-01-01

    The particulate fraction from hen brain was labelled with [3H]di-isopropyl phosphorofluoridate (DiPF) and separated by polyacrylamide-gel electrophoresis. Four radioactive protein bands (1--4) of molecular weights 155000, 92000, 60000, and 30000 were resolved. Most of the labelling of bands 2, 3 and 4 was inhibited by preincubation with Paraoxon. The residue in band 4 was sensitive to pH 5.2. Successive treatments with Paraoxon and pH 5.2 resulted in the abolition of bands 3 and 4. Bands 1 and 2 contained one and two polypeptides respectively, whose labelling was sensitive to Mipafox, but one, in band 2, was sensitive to higher concentrations of Paraoxon. The concentrations of the other two polypeptides were 6.7 and 1.95 pmol of DiPF bound/g of brain in bands 1 and 2 respectively. Both were as sensitive to Mipafox as neurotoxic esterase and were also sensitive to phenyl benzylcarbamate. 4-Nitrophenyl di-n-pentylphosphinate given in vivo inhibited neurotoxic esterase and the labelling of the band-1 polypeptide by 82% and 84% respectively, but inhibited the labelling of the band 2 polypeptide by 51%. The phosphinate in vitro produced 98% inhibition of the labelling of the band-1 polypeptide, with only 26% inhibition of the band-2 polypeptide, under conditions sufficient to inhibit neurotoxic esterase totally. Both neurotoxic esterase and the band-1 polypeptide were found in the forebrain at 1.74-fold their concentration in the rest of the brain, whereas the band-2 polypeptide was uniformly distributed. The evidence indicates that the Mipafox-sensitive polypeptide in band 1 is the [3H]DiPF-labelled active-site subunit of neurotoxic esterase. The catalytic-centre activity of the enzyme for phenyl valerate hydrolysis was found to be 2.6 x 10(5) min-1. PMID:7340807

  3. Microphase separation in thin films of lamellar forming polydisperse di-block copolymers

    SciTech Connect

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.; Chen, Jihua; Heller, William T.; Ankner, John F.; Browning, James F.; Kilbey, II, S. Michael; Sumpter, Bobby G.

    2015-02-03

    Despite the ubiquity of polydispersity in chain lengths of di-block copolymers, its effects on microphase separation in thin films have eluded a clear understanding. In this paper, we have studied effects of polydispersity on the microphase separation in thin films of lamellar forming di-block copolymers using self-consistent field theory (SCFT) and neutron reflectivity experiments. Di-block copolymers containing a polydisperse block of poly(glycidylmethacrylate) (PGMA) connected to a near-monodisperse block poly(2-vinyl-4,4-dimethyl-d6 azlactone) (PVDMA-d6) are considered in this work. Effects of chain length polydispersity, film thickness, substrate–monomer and monomer–monomer interactions on the microphase segregation are studied using SCFT. The theoretical study reveals that in comparison to a film created with monodisperse di-block copolymers, an increase in polydispersity tends to decrease the number of lamellar strata that can be packed in a film of given thickness. This is a direct consequence of an increase in lamellar domain spacing with an increase in polydispersity index. Furthermore, it is shown that polydispersity induces conformational asymmetry and an increase in the polydispersity index leads to an increase in the effective Kuhn segment length of the polydisperse blocks. It is shown that the conformational asymmetry effects, which are entropic in origin and of increasing importance as film thickness decreases, drive the polydisperse blocks to the middle of the films despite favorable substrate interactions. These predictions are verified by results from neutron reflectivity experiments on thin films made from moderately polydisperse PGMA-PVDMA-d6 di-block copolymer deposited on silicon substrates. In conclusion, results from SCFT are used to predict neutron reflectivity profiles, providing a facile and robust route to obtain useful physical insights into the structure of polydisperse diblock copolymers at

  4. DiMeX: A Text Mining System for Mutation-Disease Association Extraction.

    PubMed

    Mahmood, A S M Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases.

  5. Microphase separation in thin films of lamellar forming polydisperse di-block copolymers

    DOE PAGESBeta

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.; Chen, Jihua; Heller, William T.; Ankner, John F.; Browning, James F.; Kilbey, II, S. Michael; Sumpter, Bobby G.

    2015-02-03

    Despite the ubiquity of polydispersity in chain lengths of di-block copolymers, its effects on microphase separation in thin films have eluded a clear understanding. In this paper, we have studied effects of polydispersity on the microphase separation in thin films of lamellar forming di-block copolymers using self-consistent field theory (SCFT) and neutron reflectivity experiments. Di-block copolymers containing a polydisperse block of poly(glycidylmethacrylate) (PGMA) connected to a near-monodisperse block poly(2-vinyl-4,4-dimethyl-d6 azlactone) (PVDMA-d6) are considered in this work. Effects of chain length polydispersity, film thickness, substrate–monomer and monomer–monomer interactions on the microphase segregation are studied using SCFT. The theoretical study reveals thatmore » in comparison to a film created with monodisperse di-block copolymers, an increase in polydispersity tends to decrease the number of lamellar strata that can be packed in a film of given thickness. This is a direct consequence of an increase in lamellar domain spacing with an increase in polydispersity index. Furthermore, it is shown that polydispersity induces conformational asymmetry and an increase in the polydispersity index leads to an increase in the effective Kuhn segment length of the polydisperse blocks. It is shown that the conformational asymmetry effects, which are entropic in origin and of increasing importance as film thickness decreases, drive the polydisperse blocks to the middle of the films despite favorable substrate interactions. These predictions are verified by results from neutron reflectivity experiments on thin films made from moderately polydisperse PGMA-PVDMA-d6 di-block copolymer deposited on silicon substrates. In conclusion, results from SCFT are used to predict neutron reflectivity profiles, providing a facile and robust route to obtain useful physical insights into the structure of polydisperse diblock copolymers at interfaces.« less

  6. DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

    PubMed Central

    Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

    2014-01-01

    Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

  7. 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.

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

    DOE PAGESBeta

    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 PilZmore » 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.« less

  9. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine

    PubMed Central

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  10. 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.

  11. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine.

    PubMed

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  12. 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

  13. Cyclic di-AMP Is Critical for Listeria monocytogenes Growth, Cell Wall Homeostasis, and Establishment of Infection

    PubMed Central

    Witte, Chelsea E.; Whiteley, Aaron T.; Burke, Thomas P.; Sauer, John-Demian; Portnoy, Daniel A.; Woodward, Joshua J.

    2013-01-01

    ABSTRACT Listeria monocytogenes infection leads to robust induction of an innate immune signaling pathway referred to as the cytosolic surveillance pathway (CSP), characterized by expression of beta interferon (IFN-β) and coregulated genes. We previously identified the IFN-β stimulatory ligand as secreted cyclic di-AMP. Synthesis of c-di-AMP in L. monocytogenes is catalyzed by the diadenylate cyclase DacA, and multidrug resistance transporters are necessary for secretion. To identify additional bacterial factors involved in L. monocytogenes detection by the CSP, we performed a forward genetic screen for mutants that induced altered levels of IFN-β. One mutant that stimulated elevated levels of IFN-β harbored a transposon insertion in the gene lmo0052. Lmo0052, renamed here PdeA, has homology to a cyclic di-AMP phosphodiesterase, GdpP (formerly YybT), of Bacillus subtilis and is able to degrade c-di-AMP to the linear dinucleotide pApA. Reduction of c-di-AMP levels by conditional depletion of the di-adenylate cyclase DacA or overexpression of PdeA led to marked decreases in growth rates, both in vitro and in macrophages. Additionally, mutants with altered levels of c-di-AMP had different susceptibilities to peptidoglycan-targeting antibiotics, suggesting that the molecule may be involved in regulating cell wall homeostasis. During intracellular infection, increases in c-di-AMP production led to hyperactivation of the CSP. Conditional depletion of dacA also led to increased IFN-β expression and a concomitant increase in host cell pyroptosis, a result of increased bacteriolysis and subsequent bacterial DNA release. These data suggest that c-di-AMP coordinates bacterial growth, cell wall stability, and responses to stress and plays a crucial role in the establishment of bacterial infection. PMID:23716572

  14. ASSOCIATION OF EXPOSURE TO DI-2-ETHYLHEXYLPHTHALATE (DEHP) REPLACEMENTS WITH INCREASED BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS

    PubMed Central

    Trasande, Leonardo; Attina, Teresa M.

    2015-01-01

    Phthalates are environmental chemicals widely used in consumer and personal care products. In this study we examined associations of urinary phthalates with blood pressure, triglycerides and lipoproteins in children and adolescents, performing a cross-sectional analysis of a subsample of US children 6–19 years of age who participated in the National Health and Nutrition Examination Survey between the years 2009–2012. We quantified exposure to common environmental phthalates, with a focus on the dietary contaminant di-2-ethylhexylphthalate and two increasingly used replacements, di-isononyl phthalate and di-isodecyl phthalate, based on micromolar concentration of urinary metabolites. We assessed descriptive, univariate and multivariable associations with blood pressure and lipids. Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass, metabolites of di-2-ethylhexylphthalate , di-isononyl phthalate and di-isodecyl phthalate were associated with higher age-, gender- and height-standardized blood pressure. For each log unit increase in di-isodecyl phthalate metabolites, a 0.105 standard deviation unit increase in systolic blood pressure z score was identified (p=0.004); for di-isononyl phthalate metabolites, a 0.113 standard deviation unit increment was identified (p=0.008). For di-2-ethylhexylphthalate metabolites, a 0.103 standard deviation unit increment (p=0.013) was detected. Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products showed an association with blood pressure (≥90th percentile) in univariate analysis, but this was no longer significant in our full multivariable model, suggesting specificity. Phthalate metabolites were not associated with triglycerides or high-density lipoproteins. Further, longitudinal studies are needed to confirm these associations, and to assess opportunities for intervention. PMID:26156503

  15. Identification of a cyclic-di-GMP-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium.

    PubMed

    Rajeev, Lara; Luning, Eric G; Altenburg, Sara; Zane, Grant M; Baidoo, Edward E K; Catena, Michela; Keasling, Jay D; Wall, Judy D; Fields, Matthew W; Mukhopadhyay, Aindrila

    2014-01-01

    We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs) in Desulfovibrio vulgaris Hildenborough that are predicted to function via two-component signaling. Using purified proteins, we examined cyclic-di-GMP (c-di-GMP) production or turnover in vitro of all eight proteins. The two RRs containing only GGDEF domains (DVU2067, DVU0636) demonstrated c-di-GMP production activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains (DVU0722, DVUA0086, and DVU2933) were confirmed to be Mn(2+)-dependent phosphodiesterases (PDEs) in vitro and converted c-di-GMP to its linear form, pGpG. DVU0408, containing both c-di-GMP production (GGDEF) and degradation domains (EAL), showed c-di-GMP turnover activity in vitro also with production of pGpG. No c-di-GMP related activity could be assigned to the RR DVU0330, containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic-di-GMP-modulating RRs in the heterologous host E. coli and led to the identification of one RR, DVU0636, with increased cellulose production. Evaluation of a transposon mutant in DVU0636 indicated that the strain was impaired in biofilm formation and demonstrated an altered carbohydrate:protein ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment relative to the wild-type strain. Among the eight candidates, only the transposon disruption mutant in the DVU2067 RR presented a growth defect in liquid culture. Our results indicate that, of the two diguanylate cyclases (DGCs) that function as part of two-component signaling, DVU0636 plays an important role in biofilm formation while the function of DVU2067 has pertinence in planktonic growth.

  16. Identification of a cyclic-di-GMP-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium

    PubMed Central

    Rajeev, Lara; Luning, Eric G.; Altenburg, Sara; Zane, Grant M.; Baidoo, Edward E. K.; Catena, Michela; Keasling, Jay D.; Wall, Judy D.; Fields, Matthew W.; Mukhopadhyay, Aindrila

    2014-01-01

    We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs) in Desulfovibrio vulgaris Hildenborough that are predicted to function via two-component signaling. Using purified proteins, we examined cyclic-di-GMP (c-di-GMP) production or turnover in vitro of all eight proteins. The two RRs containing only GGDEF domains (DVU2067, DVU0636) demonstrated c-di-GMP production activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains (DVU0722, DVUA0086, and DVU2933) were confirmed to be Mn2+-dependent phosphodiesterases (PDEs) in vitro and converted c-di-GMP to its linear form, pGpG. DVU0408, containing both c-di-GMP production (GGDEF) and degradation domains (EAL), showed c-di-GMP turnover activity in vitro also with production of pGpG. No c-di-GMP related activity could be assigned to the RR DVU0330, containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic-di-GMP-modulating RRs in the heterologous host E. coli and led to the identification of one RR, DVU0636, with increased cellulose production. Evaluation of a transposon mutant in DVU0636 indicated that the strain was impaired in biofilm formation and demonstrated an altered carbohydrate:protein ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment relative to the wild-type strain. Among the eight candidates, only the transposon disruption mutant in the DVU2067 RR presented a growth defect in liquid culture. Our results indicate that, of the two diguanylate cyclases (DGCs) that function as part of two-component signaling, DVU0636 plays an important role in biofilm formation while the function of DVU2067 has pertinence in planktonic growth. PMID:25120537

  17. A direct screen for c-di-GMP modulators reveals a Salmonella Typhimurium periplasmic ʟ-arginine-sensing pathway.

    PubMed

    Mills, Erez; Petersen, Erik; Kulasekara, Bridget R; Miller, Samuel I

    2015-06-01

    Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and applied a high-throughput, real-time flow cytometry method that uses a fluorescence resonance energy transfer (FRET)-based biosensor of free c-di-GMP to screen for signals that modulate its concentration within Salmonella Typhimurium. We identified multiple compounds, including glucose, N-acetyl-d-glucosamine, salicylic acid, and ʟ-arginine, that modulated the FRET signal and therefore the free c-di-GMP concentration. By screening a library of mutants, we identified proteins required for the c-di-GMP response to each compound. Furthermore, low micromolar concentrations of ʟ-arginine induced a rapid translation-independent increase in c-di-GMP concentrations and c-di-GMP-dependent cellulose synthesis, responses that required the regulatory periplasmic domain of the diguanylate cyclase STM1987. ʟ-Arginine signaling also required the periplasmic putative ʟ-arginine-binding protein ArtI, implying that ʟ-arginine sensing occurred in the periplasm. Among the 20 commonly used amino acids, S. Typhimurium specifically responded to ʟ-arginine with an increase in c-di-GMP, suggesting that ʟ-arginine may serve as a signal during S. Typhimurium infection. Our results demonstrate that a second-messenger biosensor can be used to identify environmental signals and define pathways that alter microbial behavior.

  18. Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

    PubMed

    Miner, Kyle D; Kurtz, Donald M

    2016-02-16

    HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

  19. Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP).

    PubMed

    Kim, Henna; Youn, Suk-Jun; Kim, Seong Ok; Ko, Junsang; Lee, Jie-Oh; Choi, Byong-Seok

    2015-06-26

    Although it was only recently identified as a second messenger, c-di-AMP was found to have fundamental importance in numerous bacterial functions such as ion transport. The potassium transporter protein, KtrA, was identified as a c-di-AMP receptor. However, the co-crystallization of c-di-AMP with the protein has not been studied. Here, we determined the crystal structure of the KtrA RCK_C domain in complex with c-di-AMP. The c-di-AMP nucleotide, which adopts a U-shaped conformation, is bound at the dimer interface of RCK_C close to helices α3 and α4. c-di-AMP interacts with KtrA RCK_C mainly by forming hydrogen bonds and hydrophobic interactions. c-di-AMP binding induces the contraction of the dimer, bringing the two monomers of KtrA RCK_C into close proximity. The KtrA RCK_C was able to interact with only c-di-AMP, but not with c-di-GMP, 3',3-cGAMP, ATP, and ADP. The structure of the KtrA RCK_C domain and c-di-AMP complex would expand our understanding about the mechanism of inactivation in Ktr transporters governed by c-di-AMP.

  20. [Funzioni esecutive metacognitive ed emozionali/motivazionali nel disturbo dello spettro dell'autismo e nel disturbo da deficit di attenzione con iperattività: risultati preliminari].

    PubMed

    Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Catania, Valentina; Genitori D'Arrigo, Valentina; Di Giorgio, Rosa; Zingale, Marinella; Trubia, Grazia; Torrisi, Anna; Elia, Maurizio

    2016-01-01

    RIASSUNTO. Scopo. I deficit delle funzioni esecutive (FE) sono frequentemente osservati nei disturbi dello spettro dell'autismo (ASD) e nel disturbo da deficit di attenzione con iperattività (ADHD). Lo scopo di questo studio è quello di valutare e confrontare le funzioni esecutive metacognitive ed emozionali/motivazionali di bambini con ASD e ADHD, sia fra di loro che con un gruppo di controllo. Metodi. Il campione è costituito da un totale di 58 soggetti, di cui 17 con ASD senza disabilità intellettiva, 18 con ADHD-manifestazione combinata e 23 con sviluppo tipico, abbinati per genere, età cronologica e livello intellettivo. Le valutazioni hanno riguardato alcune aree del funzionamento esecutivo, nello specifico pianificazione, flessibilità mentale, generatività e inibizione della risposta, che rappresentano sia le funzioni esecutive metacognitive sia quelle emozionali/motivazionali. Risultati. I risultati hanno rilevato un'ampia sovrapposizione delle disfunzioni esecutive nei due gruppi clinici con ASD e ADHD, e non sono stati indicativi della presenza di due profili realmente distinti del funzionamento esecutivo. Tuttavia, nell'ADHD è stato trovato un deficit più severo nell'inibizione della risposta prepotente (funzione emozionale/motivazionale). Conclusioni. I risultati del nostro studio sono parzialmente in accordo con quelli della letteratura. Ulteriori ricerche con gruppi più numerosi potranno chiarire più approfonditamente quali punti di forza e debolezza, nell'ampio spettro delle funzioni esecutive, differenzino fra loro le prestazioni di persone con ASD e ADHD. PMID:27362821

  1. [Funzioni esecutive metacognitive ed emozionali/motivazionali nel disturbo dello spettro dell'autismo e nel disturbo da deficit di attenzione con iperattività: risultati preliminari].

    PubMed

    Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Catania, Valentina; Genitori D'Arrigo, Valentina; Di Giorgio, Rosa; Zingale, Marinella; Trubia, Grazia; Torrisi, Anna; Elia, Maurizio

    2016-01-01

    RIASSUNTO. Scopo. I deficit delle funzioni esecutive (FE) sono frequentemente osservati nei disturbi dello spettro dell'autismo (ASD) e nel disturbo da deficit di attenzione con iperattività (ADHD). Lo scopo di questo studio è quello di valutare e confrontare le funzioni esecutive metacognitive ed emozionali/motivazionali di bambini con ASD e ADHD, sia fra di loro che con un gruppo di controllo. Metodi. Il campione è costituito da un totale di 58 soggetti, di cui 17 con ASD senza disabilità intellettiva, 18 con ADHD-manifestazione combinata e 23 con sviluppo tipico, abbinati per genere, età cronologica e livello intellettivo. Le valutazioni hanno riguardato alcune aree del funzionamento esecutivo, nello specifico pianificazione, flessibilità mentale, generatività e inibizione della risposta, che rappresentano sia le funzioni esecutive metacognitive sia quelle emozionali/motivazionali. Risultati. I risultati hanno rilevato un'ampia sovrapposizione delle disfunzioni esecutive nei due gruppi clinici con ASD e ADHD, e non sono stati indicativi della presenza di due profili realmente distinti del funzionamento esecutivo. Tuttavia, nell'ADHD è stato trovato un deficit più severo nell'inibizione della risposta prepotente (funzione emozionale/motivazionale). Conclusioni. I risultati del nostro studio sono parzialmente in accordo con quelli della letteratura. Ulteriori ricerche con gruppi più numerosi potranno chiarire più approfonditamente quali punti di forza e debolezza, nell'ampio spettro delle funzioni esecutive, differenzino fra loro le prestazioni di persone con ASD e ADHD.

  2. The soybean GmDi19-5 interacts with GmLEA3.1 and increases sensitivity of transgenic plants to abiotic stresses

    PubMed Central

    Feng, Zhi-Juan; Cui, Xiao-Yu; Cui, Xi-Yan; Chen, Ming; Yang, Guang-Xiao; Ma, You-Zhi; He, Guang-Yuan; Xu, Zhao-Shi

    2015-01-01

    Drought-induced (Di19) proteins played important roles in plant growth, development, and abiotic stress responses. In the present study, a total of seven Di19 genes were identified in soybean. Each soybean Di19 gene showed specific responses to salt, drought, oxidative, and ABA stresses based on expression profiles. With a relatively higher transcript level among Di19 members under four stress treatments, GmDi19-5 was selected for detailed analysis. Inhibitor assays revealed that ABA inhibitor (Fluridone) or H2O2 inhibitor (DMTU) was involved in the drought- or salt-induced transcription of GmDi19-5. The GUS activity driven by the GmDi19-5 promoter was induced by salt, PEG, ABA, and MV treatments and tended to be accumulated in the vascular bundles and young leaves. A subcellular localization assay showed that GmDi19-5 protein localized in the nucleus. Further investigation showed that GmDi19-5 protein was involved in the interaction with GmLEA3.1. Overexpression of GmDi19-5 increased sensitivity of transgenic Arabidopsis plants to salt, drought, oxidative, and ABA stresses and regulated expression of several ABA/stress-associated genes. This present investigation showed that GmDi19-5 functioned as a negative factor under abiotic stresses and was involved in ABA and SOS signaling pathway by altering transcription of stress-associated genes. PMID:25852726

  3. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system.

    PubMed

    Shu, Chang; Yi, Guanghui; Watts, Tylan; Kao, C Cheng; Li, Pingwei

    2012-06-24

    STING (stimulator of interferon genes) is an innate immune sensor of cyclic dinucleotides that regulates the induction of type I interferons. STING's C-terminal domain forms a V-shaped dimer and binds a cyclic diguanylate monophosphate (c-di-GMP) at the dimer interface by both direct and solvent-mediated hydrogen bonds. Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling.

  4. A cytotoxic principle of Tamarindus indica, di-n-butyl malate and the structure-activity relationship of its analogues.

    PubMed

    Kobayashi, A; Adenan, M I; Kajiyama, S; Kanzaki, H; Kawazu, K

    1996-01-01

    Bioassay-guided fractionation of the methanolic extract of Tamarindus indica fruits led to the isolation of L-(-)-di-n-butyl malate which exhibited a pronounced cytotoxic activity against sea urchin embryo cells. In order to study structure-activity relationships, close-structure relatives of di-n-butyl malate were synthesized using D-(+)- and L-(-)-malic acid as starting materials, and their cytotoxic activities were examined for the sea urchin embryo assay. L-(-)-Di-n-pentyl malate was the most effective inhibitor to the development of the fertilized eggs. Significant inhibitory activity was not seen in the esters of D-(-)-isomer.

  5. THE STATE OF MANGANESE IN THE PHOTOSYNTHETIC APPARATUS. I. EXAFS STUDIES ON CHLOROPLASTS AND di-u-oxo BRIDGED di-MANGANESE MODEL COMPOUNDS

    SciTech Connect

    Kirby, J. A.; Robertson, A. S.; Smith, J. P.; Thompson, A. C.; Thompson, A. C.; Klein, M. P.

    1980-11-01

    Extended X-ray Absorption Fine Structure (EXAFS) studies on the manganese contained in spinach chloroplasts and on certain di-u-oxo bridged manganese dimers of the form (X{sub 2}Mn)O{sub 2}(MnX{sub 2} (X=2,2'-bypyridine and 1,10-phenanthroline) are reported. From these studies, the manganese associated with photosynthetic oxygen evolution is suggested to occur as a bridged transition metal dimer with most likely another manganese. Extensive details on the analysis are included.

  6. Atomistic Study of the Migration of Di- and Tri-Interstitials in Silicon

    SciTech Connect

    Posselt, Matthias; Gao, Fei; Zwicker, D

    2005-06-22

    A comprehensive study on the migration of di- and tri-interstitials in silicon is performed using classical molecular dynamics simulations with a Stillinger-Weber potential. At first the structures and energetics of the di- and the tri-interstitial are investigated, and the accuracy of the interatomic potential is tested by comparing the results with literature data obtained by tight-binding and density-functional-theory calculations. Then the migration is investigated for temperatures between 800 and 1600 K. Very long simulation times, large computational cells and different initial conditions are considered. The defect diffusivity, the self-diffusion coefficient per defect and the corresponding effective migration barriers are calculated. Compared to a mono-interstitial, the di-interstitial migrates faster, whereas the tri-interstitial diffuses slower. The mobility of the di- and the mono-interstitial is higher than the mobility of the lattice atoms during the diffusion of these defects. On the other hand, the tri-interstitial mobility is lower than the corresponding atomic mobility. The migration mechanism of the di-interstitial shows a pronounced dependence on the temperature. At low temperature a high mobility on zigzag-like lines along a <110> axis within a {l_brace}110{r_brace} plane is found, whereas the change between equivalent <110> directions or equivalent {l_brace}110{r_brace} planes occurs seldomly and requires a long simulation time, but the rate of directional change increases with increasing temperature. During the diffusion within {l_brace}110{r_brace} planes the di-interstitial moves like a wave packet so that the atomic mobility is lower than that of the defect. On the other hand, the change between equivalent {l_brace}110{r_brace} migration planes is characterized by frequent atomic rearrangements. The visual analysis of the tri-interstitial diffusion reveals complex migration mechanisms and a high atomic mobility. The diffusivities and

  7. Crystal structure of tri-aqua-(2,6-di-methyl-pyrazine-κN (4))bis-(thio-cyanato-κN)manganese(II) 2,5-di-methyl-pyrazine disolvate.

    PubMed

    Suckert, Stefan; Wöhlert, Susanne; Jess, Inke; Näther, Christian

    2015-12-01

    In the crystal structure of the title complex, [Mn(NCS)2(C6H8N2)(H2O)3]·2C6H8N2, the Mn(II) cation is coordinated by two terminally N-bonded thio-cyanate anions, three water mol-ecules and one 2,6-di-methyl-pyrazine ligand within a slightly distorted N3O3 octa-hedral geometry; the entire complex mol-ecule is generated by the application of a twofold rotation axis. The asymmetric unit also contains an uncoordinating 2,5-di-methyl-pyrazine ligand in a general position. Obviously, the coordination to the 2,6-di-methyl-pyrazine ligand is preferred because coordination to the 2,5-di-methyl-pyrazine is hindered due to the bulky methyl group proximate to the N atom. The discrete complexes are linked by water-O-H⋯N(2,6-di-methyl-pyzazine/2,5-di-methyl-pyza-zine) hydrogen bonding, forming a three-dimensional network. In the crystal, mol-ecules are arranged in a way that cavities are formed in which unspecified, disordered solvent molecules reside. These were modelled employing the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The composition of the unit cell does not take into account the presence of the unspecified solvent.

  8. Crystal structure of tri-aqua-(2,6-di-methyl-pyrazine-κN (4))bis-(thio-cyanato-κN)manganese(II) 2,5-di-methyl-pyrazine disolvate.

    PubMed

    Suckert, Stefan; Wöhlert, Susanne; Jess, Inke; Näther, Christian

    2015-12-01

    In the crystal structure of the title complex, [Mn(NCS)2(C6H8N2)(H2O)3]·2C6H8N2, the Mn(II) cation is coordinated by two terminally N-bonded thio-cyanate anions, three water mol-ecules and one 2,6-di-methyl-pyrazine ligand within a slightly distorted N3O3 octa-hedral geometry; the entire complex mol-ecule is generated by the application of a twofold rotation axis. The asymmetric unit also contains an uncoordinating 2,5-di-methyl-pyrazine ligand in a general position. Obviously, the coordination to the 2,6-di-methyl-pyrazine ligand is preferred because coordination to the 2,5-di-methyl-pyrazine is hindered due to the bulky methyl group proximate to the N atom. The discrete complexes are linked by water-O-H⋯N(2,6-di-methyl-pyzazine/2,5-di-methyl-pyza-zine) hydrogen bonding, forming a three-dimensional network. In the crystal, mol-ecules are arranged in a way that cavities are formed in which unspecified, disordered solvent molecules reside. These were modelled employing the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The composition of the unit cell does not take into account the presence of the unspecified solvent. PMID:26870435

  9. Vibrio cholerae VpsT Regulates Matrix Production and Motility by Directly Sensing Cyclic di-GMP

    SciTech Connect

    Krasteva, P.; Fong, J; Shikuma, N; Beyhan, S; Navarro, M; Yildiz, F; Sondermann, H

    2010-01-01

    Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerization on c-di-GMP binding.

  10. A Versatile Room-Temperature Route to Di- and Trisubstituted Allenes Using Flow-Generated Diazo Compounds.

    PubMed

    Poh, Jian-Siang; Tran, Duc N; Battilocchio, Claudio; Hawkins, Joel M; Ley, Steven V

    2015-06-26

    A copper-catalyzed coupling reaction between flow-generated unstabilized diazo compounds and terminal alkynes provides di- and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups.

  11. Bromine Incorporation in Regulated and Emerging DBPs and the Relative Predominance of Mono, Di and Trihalogenated DBPs - SLIDES

    EPA Science Inventory

    Examination of bromine incorporation in emerging DBPs vs that of regulated DBPs Study of predominance of di- vs trihalogenated species in different DBP classes Better understand and characterize exposure to DBPs of health concern

  12. [Networks involving quorum sensing, cyclic-di-GMP and nitric oxide on biofilm production in bacteria].

    PubMed

    Ramírez-Mata, Alberto; Fernández-Domínguez, Ileana J; Nuñez-Reza, Karen J; Xiqui-Vázquez, María L; Baca, Beatriz E

    2014-01-01

    Bacterial biofilms are ubiquitous in nature, and their flexibility is derived in part from a complex extracellular matrix that can be made-to-order to cope with environmental demand. Although common developmental stages leading to biofilm formation have been described, an in-depth knowledge of genetic and signaling is required to understand biofilm formation. Bacteria detect changes in population density by quorum sensing and particular environmental conditions, using signals such as cyclic di-GMP or nitric oxide. The significance of understanding these signaling pathways lies in that they control a broad variety of functions such as biofilm formation, and motility, providing benefits to bacteria as regards host colonization, defense against competitors, and adaptation to changing environments. Due to the importance of these features, we here review the signaling network and regulatory connections among quorum sensing, c-di-GMP and nitric oxide involving biofilm formation.

  13. Preparation and structural elucidation of (-)-tetrahydroberberine-(+)-2,3-di( p-toluyl) tartaric acid complex

    NASA Astrophysics Data System (ADS)

    Gao, Jin-Ming; Liu, Wei-Tao; Li, Man-Lin; Liu, Han-Wei; Zhang, Xing-Chang; Li, Zong-Xiao

    2008-12-01

    A new (2:1) complex of (-)-13a S-tetrahydroberberine [(-)-13a S-THB] with (+)-2,3-di( p-toluyl) tartaric acid (DTTA), i.e. 5,8,13,13a-tetrahydro-9,10-dimethoxy-2,3-methylenedioxy- 6H dibenzo[a,g] quinolizine·2,3-di( p-toluyl) tartaric acid [2C 20H 20NO 4·C 20H 18O 8], as well as its optical active component (-)-THB, has been obtained from the resolution process of (±)-THB in methanol. The structures of this complex and an enantiomer (-)-13a S-THB have been characterized by CD, IR and NMR spectroscopy as well as by X-ray single crystal diffraction.

  14. Simulating water, solute, and heat transport in the subsurface with the VS2DI software package

    USGS Publications Warehouse

    Healy, R.W.

    2008-01-01

    The software package VS2DI was developed by the U.S. Geological Survey for simulating water, solute, and heat transport in variably saturated porous media. The package consists of a graphical preprocessor to facilitate construction of a simulation, a postprocessor for visualizing simulation results, and two numerical models that solve for flow and solute transport (VS2DT) and flow and heat transport (VS2DH). The finite-difference method is used to solve the Richards equation for flow and the advection-dispersion equation for solute or heat transport. This study presents a brief description of the VS2DI package, an overview of the various types of problems that have been addressed with the package, and an analysis of the advantages and limitations of the package. A review of other models and modeling approaches for studying water, solute, and heat transport also is provided. ?? Soil Science Society of America. All rights reserved.

  15. Carbon Nanofiber Incorporated Silica Based Aerogels with Di-Isocyanate Cross-Linking

    NASA Technical Reports Server (NTRS)

    Vivod, Stephanie L.; Meador, Mary Ann B.; Capadona, Lynn A.; Sullivan, Roy M.; Ghosn, Louis J.; Clark, Nicholas; McCorkle, Linda

    2008-01-01

    Lightweight materials with excellent thermal insulating properties are highly sought after for a variety of aerospace and aeronautic applications. (1) Silica based aerogels with their high surface area and low relative densities are ideal for applications in extreme environments such as insulators for the Mars Rover battery. (2) However, the fragile nature of aerogel monoliths prevents their widespread use in more down to earth applications. We have shown that the fragile aerogel network can be cross-linked with a di-isocyanate via amine decorated surfaces to form a conformal coating. (3) This coating reinforces the neck regions between secondary silica particles and significantly strengthens the aerogels with only a small effect on density or porosity. Scheme 1 depicts the cross-linking reaction with the di-isocyanate and exhibits the stages that result in polymer cross-linked aerogel monoliths.

  16. Introducing DVM: DiVersity Matters (an Association of American Veterinary Medical Colleges Initiative).

    PubMed

    Greenhill, Lisa M

    2007-01-01

    Now more than ever, colleges of veterinary medicine (CVMs) are challenged to improve the educational experience, build environments that support long-term student and faculty success, and create a diverse and competitive workforce. Additionally, the nation's fast-evolving racial and ethnic demographics demand that the veterinary medical profession be responsive to the emerging needs of this changing population. In March 2005, during the 15th Iverson Bell Symposium, the Association of American Veterinary Medical Colleges (AAVMC) unveiled its DiVersity Matters (DVM) initiative, designed to bring the CVMs closer to achieving these goals. Several key objectives of the initiative and their possible long-term significance to success of the DiVersity Matters initiative are explored here, and CVMs are encouraged to expand efforts to increase racial and ethnic diversity in academic veterinary medicine.

  17. Deubiquitinating Enzyme Specificity for Ubiquitin Chain Topology Profiled by Di-Ubiquitin Activity Probes

    PubMed Central

    McGouran, Joanna F.; Gaertner, Selina R.; Altun, Mikael; Kramer, Holger B.; Kessler, Benedikt M.

    2013-01-01

    Summary Posttranslational modification with ubiquitin (Ub) controls many cellular processes, and aberrant ubiquitination can contribute to cancer, immunopathology, and neurodegeneration. The versatility arises from the ability of Ub to form polymer chains with eight distinct linkages via lysine side chains and the N terminus. In this study, we engineered Di-Ub probes mimicking all eight different poly-Ub linkages and profiled the deubiquitinating enzyme (DUB) selectivity for recognizing Di-Ub moieties in cellular extracts. Mass spectrometric profiling revealed that most DUBs examined have broad selectivity, whereas a subset displays a clear preference for recognizing noncanonical over K48/K63 Ub linkages. Our results expand knowledge of Ub processing enzyme functions in cellular contexts that currently depends largely on using recombinant enzymes and substrates. PMID:24290882

  18. On-line process analysis innovation: DiComp (tm) shunting dielectric sensor technology

    NASA Technical Reports Server (NTRS)

    Davis, Craig R.; Waldman, Frank A.

    1993-01-01

    The DiComp Shunting Dielectric Sensor (SDS) is a new patent-pending technology developed under the Small Business Innovation Research Program (SBIR) for NASA's Kennedy Space Center. The incorporation of a shunt electrode into a conventional fringing field dielectric sensor makes the SDS uniquely sensitive to changes in material dielectric properties in the KHz to MHz range which were previously detectable only at GHz measurement frequencies. The initial NASA application of the SDS for Nutrient Delivery Control has demonstrated SDS capabilities for thickness and concentration measurement of Hoagland nutrient solutions. The commercial introduction of DiComp SDS technology for concentration and percent solids measurements in dispersions, emulsions and solutions represents a new technology for process measurements for liquids in a variety of industries.

  19. Contribution of di-SIA to mass transport in Fe-Cr alloys

    NASA Astrophysics Data System (ADS)

    Ryabov, V. A.; Pechenkin, V. A.; Molodtsov, V. L.; Terentyev, D.

    2016-04-01

    Molecular dynamics simulations have been performed to study the diffusion characteristics of di-self interstitial atom (di-SIA) in BCC Fe-Cr alloys and corresponding mass transport of Fe and Cratoms in the temperature range 600-1000 K in the alloys with Cr content 5-25 at%, which is relevant for ferritic/martensitic steels. An original treatment is proposed in this work to account for a mixed migration mode composed of the diffusion of the cluster itself and break-up into a pair of independent SIAs. The ratio of self-diffusion coefficients of Cr and Fe is found to exceed unity in Fe-5Cr and Fe-10Cr alloys, which implies that under cascade-producing damage, 3D-migrating small SIA clusters will effectively contribute to the segregation of Cr to neutral and SIA-preferential sinks, eventually causing radiation induced segregation.

  20. Traceability of 'Limone di Siracusa PGI' by a multidisciplinary analytical and chemometric approach.

    PubMed

    Amenta, M; Fabroni, S; Costa, C; Rapisarda, P

    2016-11-15

    Food traceability is increasingly relevant with respect to safety, quality and typicality issues. Lemon fruits grown in a typical lemon-growing area of southern Italy (Siracusa), have been awarded the PGI (Protected Geographical Indication) recognition as 'Limone di Siracusa'. Due to its peculiarity, consumers have an increasing interest about this product. The detection of potential fraud could be improved by using the tools linking the composition of this production to its typical features. This study used a wide range of analytical techniques, including conventional techniques and analytical approaches, such as spectral (NIR spectra), multi-elemental (Fe, Zn, Mn, Cu, Li, Sr) and isotopic ((13)C/(12)C, (18)O/(16)O) marker investigations, joined with multivariate statistical analysis, such as PLS-DA (Partial Least Squares Discriminant Analysis) and LDA (Linear Discriminant Analysis), to implement a traceability system to verify the authenticity of 'Limone di Siracusa' production. The results demonstrated a very good geographical discrimination rate. PMID:27283690

  1. Di-Higgs decay of stoponium at a future photon-photon collider

    NASA Astrophysics Data System (ADS)

    Ito, Hayato; Moroi, Takeo; Takaesu, Yoshitaro

    2016-05-01

    We study the detectability of the stoponium in the di-Higgs decay mode at the photon-photon collider option of the International e+e- Linear Collider, the center-of-mass energy of which is planned to reach ˜1 TeV . We find that 5 σ detection of the di-Higgs decay mode is possible with the integrated electron-beam luminosity of 1 ab-1 if the signal cross section, σ (γ γ →σt˜1→h h ) , of O (0.1 ) fb is realized for the stoponium mass smaller than ˜800 GeV at 1 TeV ILC. Such a value of the cross section can be realized in the minimal supersymmetric standard model with relatively large trilinear stop-stop-Higgs coupling constant. The implication of the stoponium cross section measurement for the minimal supersymmetric standard model stop sector is also discussed.

  2. Adsorption of di-l-alanine on Cu(110) investigated with scanning tunneling microscopy [rapid communication

    NASA Astrophysics Data System (ADS)

    Stensgaard, I.

    2003-11-01

    Sub-monolayer growth of a small chiral peptide, di- L-alanine, on Cu(1 1 0) was investigated by variable temperature scanning tunneling microscopy (STM). At low coverage and for temperatures above ≈-220 K the molecules nucleate along the [ 3¯ 3 2] direction to form short, mainly one-dimensional islands. An increase in coverage leads to the formation of [ 3¯ 3 2]-directed, elongated islands. Images with sub-molecular resolution reveal that the orientation of the molecules within one particular island depends on the deposition temperature. At higher coverage, up to one monolayer, the islands coalesce, giving rise to phase boundaries between domains of opposite orientation. An atomic-scale model for di- L-alanine on Cu(1 1 0) is presented.

  3. Synthesis and DFT calculation of a novel 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene.

    PubMed

    Bayrakdar, A; Kart, H H; Elcin, S; Deligoz, H; Karabacak, M

    2015-02-01

    In this study, 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene has been synthesized from 2-aminoantracene and 25,27-dihydroxy-26,28-diethylacetate calix[4]arene. In order to identify the molecular structure and vibrational features of the prepared azocalix[4]arene, FT-IR and (1)H NMR spectral data have been used. FT-IR spectrum of the studied molecule is recorded in the region 4000-400 cm(-1). (1)H NMR spectrum is recorded for 0.1-0.2 M solutions in DMSO-d6 solution. The molecular geometry, infrared spectrum are calculated by the density functional method employing B3LYP level with different basis sets, including 6-31G(d) and LanL2DZ. The chemical shifts calculation for (1)H NMR of the title molecule is calculated by using by Gauge-Invariant Atomic Orbital method by utilizing the same basis sets. The total density of state, the partial density of state and the overlap population density of state diagram analysis are done via GaussSum 3.0 program. Frontier molecular orbital (HOMO-LUMO) and molecular electrostatic potential surface on the title molecule are carried out for various intramolecular interactions that are responsible for the stabilization of the molecule. The experimental results and theoretical calculations have been compared, and they are found to be in good agreement. PMID:25448961

  4. Assessing differences in toxicity and teratogenicity of three phthalates, Diethyl phthalate, Di-n-propyl phthalate, and Di-n-butyl phthalate, using Xenopus laevis embryos.

    PubMed

    Gardner, Steven T; Wood, Andrew T; Lester, Rachel; Onkst, Paitra E; Burnham, Nathaniel; Perygin, Donna H; Rayburn, James

    2016-01-01

    Phthalates, compounds used to add flexibility to plastics, are ubiquitous in the environment. In particular, the diethyl (DEP), di-n-propyl (DnPP), and di-n-butyl (DBP) phthalates were found to exert detrimental effects in both mammalian and non-mammalian studies, with toxic effects varying according to alkyl chain length. Embryos of Xenopus laevis, the African clawed frog, have been used to assess toxicity and teratogenicity of several compounds and serves as a model for assessing adverse and teratogenic effects of ortho-phthalate esters. The purpose of this study was to develop a model for comparison of developmentally toxic effects of ortho-phthalate esters using Xenopus embryos. In this study developing Xenopus laevis embryos were exposed to increasing concentrations of DEP, DnPP, and DBP using the 96-h Frog Embryo Teratogenesis Assay-Xenopus (FETAX), with 96-h lethal concentrations, effective concentrations to induce malformations, teratogenic indices, and concentrations to inhibit growth determined. DEP, DnPP, and DBP showed enhanced toxicity with increasing ester length. Developing Xenopus laevis exposed to DEP, DnPP, and DBP showed similar malformations that also occurred at lower concentrations with increasing alkyl chain length. Teratogenic risk did not change markedly with alkyl chain length, with data showing only DBP to be teratogenic.

  5. N-[(2,6-Di­ethyl­phen­yl)carbamo­thio­yl]-2,2-di­phenyl­acetamide

    PubMed Central

    Yusof, Mohd Sukeri Mohd; Razali, Nur Rafikah; Arshad, Suhana; Rahman, Azhar Abdul; Razak, Ibrahim Abdul

    2013-01-01

    In the title compound, C25H26N2OS, the diethyl-substituted benzene ring forms dihedral angles of 67.38 (9) and 55.32 (9)° with the terminal benzene rings. The mol­ecule adopts a trans–cis conformation with respect to the orientations of the di­phenyl­methane and 1,3-di­ethyl­benzene groups with respect to the S atom across the C—N bonds. This conformation is stabilized by an intra­molecular N—H⋯O hydrogen bond, which generates an S(6) ring. In the crystal, pairs of N—H⋯S hydrogen bonds link the mol­ecules into inversion dimers, forming R 2 2(6) loops. The dimer linkage is reinforced by a pair of C—H⋯S hydrogen bonds, which generate R 2 2(8) loops. Weak C—H⋯π and π–π [centroid–centroid seperation = 3.8821 (10) Å] inter­actions also occur in the crystal structure. PMID:23795124

  6. Pharmacokinetic Study of Di-Phenyl-Di-(2,4-Difluobenzohydroxamato)Tin(IV): Novel Metal-Based Complex with Promising Antitumor Potential.

    PubMed

    Li, Yunlan; Gao, Zhuyan; Guo, Pu; Li, Qingshan

    2012-01-01

    Di-phenyl-di-(2,4-difluobenzohydroxamato)tin(IV)(DPDFT), a new metal-based arylhydroxamate antitumor complex, showed high in vivo and in vitro antitumor activity with relative low toxicity, but no data was reported regarding its pharmacokinetics and dependent toxicity. In this paper, a rapid, sensitive, and reproducible HPLC method in vivo using Diamonsil ODS column with a mixture of methanol and phosphoric acid in water (30 : 70, V/V, pH 3.0) as mobile phase was developed and validated for the determination of DPDFT. The plasma was deproteinized with methanol that contained acetanilide as the internal standard (I.S.). The photodiode array detector was set at a wavelength of 228 nm at room temperature and a linear curve over the concentration range 0.1~25 μg·mL(-1) (r = 0.9993) was obtained. The method was used to determine the concentration-time profiles for DPDFT in the plasma after single intravenous administration with doses of 5, 10, 15 mg·kg(-1) to rats. The pharmacokinetics parameter calculations and modeling were carried out using the 3p97 software. The results showed that the concentration-time curves of DPDFT in rat plasma could be fitted to two-compartment model. PMID:22400014

  7. Synthesis and DFT calculation of a novel 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene.

    PubMed

    Bayrakdar, A; Kart, H H; Elcin, S; Deligoz, H; Karabacak, M

    2015-02-01

    In this study, 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene has been synthesized from 2-aminoantracene and 25,27-dihydroxy-26,28-diethylacetate calix[4]arene. In order to identify the molecular structure and vibrational features of the prepared azocalix[4]arene, FT-IR and (1)H NMR spectral data have been used. FT-IR spectrum of the studied molecule is recorded in the region 4000-400 cm(-1). (1)H NMR spectrum is recorded for 0.1-0.2 M solutions in DMSO-d6 solution. The molecular geometry, infrared spectrum are calculated by the density functional method employing B3LYP level with different basis sets, including 6-31G(d) and LanL2DZ. The chemical shifts calculation for (1)H NMR of the title molecule is calculated by using by Gauge-Invariant Atomic Orbital method by utilizing the same basis sets. The total density of state, the partial density of state and the overlap population density of state diagram analysis are done via GaussSum 3.0 program. Frontier molecular orbital (HOMO-LUMO) and molecular electrostatic potential surface on the title molecule are carried out for various intramolecular interactions that are responsible for the stabilization of the molecule. The experimental results and theoretical calculations have been compared, and they are found to be in good agreement.

  8. Synthesis and DFT calculation of a novel 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene

    NASA Astrophysics Data System (ADS)

    Bayrakdar, A.; Kart, H. H.; Elcin, S.; Deligoz, H.; Karabacak, M.

    2015-02-01

    In this study, 5,17-di(2-antracenylazo)-25,27-di(ethoxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene has been synthesized from 2-aminoantracene and 25,27-dihydroxy-26,28-diethylacetate calix[4]arene. In order to identify the molecular structure and vibrational features of the prepared azocalix[4]arene, FT-IR and 1H NMR spectral data have been used. FT-IR spectrum of the studied molecule is recorded in the region 4000-400 cm-1. 1H NMR spectrum is recorded for 0.1-0.2 M solutions in DMSO-d6 solution. The molecular geometry, infrared spectrum are calculated by the density functional method employing B3LYP level with different basis sets, including 6-31G(d) and LanL2DZ. The chemical shifts calculation for 1H NMR of the title molecule is calculated by using by Gauge-Invariant Atomic Orbital method by utilizing the same basis sets. The total density of state, the partial density of state and the overlap population density of state diagram analysis are done via GaussSum 3.0 program. Frontier molecular orbital (HOMO-LUMO) and molecular electrostatic potential surface on the title molecule are carried out for various intramolecular interactions that are responsible for the stabilization of the molecule. The experimental results and theoretical calculations have been compared, and they are found to be in good agreement.

  9. Comparison of hepatic peroxisome proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate with a hypolipidemic drug.

    PubMed Central

    Reddy, J K; Reddy, M K; Usman, M I; Lalwani, N D; Rao, M S

    1986-01-01

    Peroxisome proliferation is inducible in hepatocytes of rodent and nonrodent species by structurally dissimilar hypolipidemic drugs and certain phthalate ester plasticizers. The induction of peroxisome proliferation appears to be a tissue specific response limited largely to the hepatocyte. Peroxisome proliferation is associated with increases in the activity of the H2O2-generating peroxisomal fatty acid beta-oxidation system and in the amount of peroxisome proliferation-associated 80,000 MW polypeptide (PPA-80). Chronic administration of these non-DNA damaging and nonmutagenic peroxisome proliferators to rats and mice results in the development of hepatocellular carcinomas. Comparative morphometric and biochemical data from rats treated with varying dose levels of ciprofibrate, a hypolipidemic drug, and di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate, the widely used plasticizers, indicate that the hepatocarcinogenic potency of these agents is correlatable with their ability to induce peroxisome proliferation, peroxisomal beta-oxidation and PPA-80. Available evidence strongly favors the role of peroxisome proliferation-associated oxidative stress in the induction of liver tumors by peroxisome proliferators. Images FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 7. FIGURE 10. A FIGURE 10. B PMID:3709457

  10. A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

    PubMed Central

    Skotnicka, Dorota; Trampari, Eleftheria; Liang, Jennifer; Kaever, Volkhard; Malone, Jacob G.; Singer, Mitchell; Søgaard-Andersen, Lotte

    2016-01-01

    Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-di-GMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus. PMID:27214040

  11. 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

  12. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    PubMed Central

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; Harwood, Caroline S.; Sondermann, Holger; Navarro, Marcos V. A. S.

    2016-01-01

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs. PMID:26712005

  13. Motor and dorsal root ganglion axons serve as choice points for the ipsilateral turning of dI3 axons.

    PubMed

    Avraham, Oshri; Hadas, Yoav; Vald, Lilach; Hong, Seulgi; Song, Mi-Ryoung; Klar, Avihu

    2010-11-17

    The axons of the spinal intersegmental interneurons are projected longitudinally along various funiculi arrayed along the dorsal-ventral axis of the spinal cord. The roof plate and the floor plate have a profound role in patterning their initial axonal trajectory. However, other positional cues may guide the final architecture of interneuron tracks in the spinal cord. To gain more insight into the organization of specific axonal tracks in the spinal cord, we focused on the trajectory pattern of a genetically defined neuronal population, dI3 neurons, in the chick spinal cord. Exploitation of newly characterized enhancer elements allowed specific labeling of dI3 neurons and axons. dI3 axons are projected ipsilaterally along two longitudinal fascicules at the ventral lateral funiculus (VLF) and the dorsal funiculus (DF). dI3 axons change their trajectory plane from the transverse to the longitudinal axis at two novel checkpoints. The axons that elongate at the DF turn at the dorsal root entry zone, along the axons of the dorsal root ganglion (DRG) neurons, and the axons that elongate at the VLF turn along the axons of motor neurons. Loss and gain of function of the Lim-HD protein Isl1 demonstrate that Isl1 is not required for dI3 cell fate. However, Isl1 is sufficient to impose ipsilateral turning along the motor axons when expressed ectopically in the commissural dI1 neurons. The axonal patterning of dI3 neurons, revealed in this study, highlights the role of established axonal cues-the DRG and motor axons-as intermediate guidepost cues for dI3 axons.

  14. A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

    PubMed

    Skotnicka, Dorota; Smaldone, Gregory T; Petters, Tobias; Trampari, Eleftheria; Liang, Jennifer; Kaever, Volkhard; Malone, Jacob G; Singer, Mitchell; Søgaard-Andersen, Lotte

    2016-05-01

    Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-di-GMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be-at least partially-functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus.

  15. Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa.

    PubMed

    Matsuyama, Bruno Y; Krasteva, Petya V; Baraquet, Claudine; Harwood, Caroline S; Sondermann, Holger; Navarro, Marcos V A S

    2016-01-12

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ(54)-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ's AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP-complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.

  16. Gas chromatographic analysis of synthetic glycidol esters, mono-, di- and triglycerides.

    PubMed

    Engbersen, J A; van Stijn, F

    1976-03-01

    The gas chromatographic analysis of glycidol esters and mono-, di-,and triglycerides of palmitic-, stearic-, and oleic acid mixtures is described. The composition of the products was determined by gas chromatography on OV-17 after trimethylsilylation. Base-line separations between 1- and 2-monoglycerides and between 1,2- and 1,3-diglycerides were obtained. Isomerisation of the trimethylsilyl ethers of monoglycerides was not observed, contrary to published work.

  17. Photochemistry of amorphous 1,2-di-(α-naphthyl)ethylene

    NASA Astrophysics Data System (ADS)

    Rachinsky, A. G.; Razumov, V. F.

    1994-03-01

    Photochemical reactions of the amorphous cis- and trans-1,2-di-(α-naphthyl)ethylenes (DαNE) in hydrosols were studied. Besides the cis—trans-photoisomerization and photocyclization taking place in solution, the amorphous DαNE was found to undergo dimerization, in this case the dimer is formed only from trans-DαNE. Efficient electronic excitation transfer from the trans- to the cis-isomer was found to occur.

  18. ParaDiS on BlueGene/L: scalable line dynamics

    SciTech Connect

    Bulatov, V; Cai, W; Fier, J; Hiratani, M; Pierce, T; Tang, M; Rhee, M; Yates, R K; Arsenlis, A

    2004-04-29

    We describe an innovative highly parallel application program, ParaDiS, which computes the plastic strength of materials by tracing the evolution of dislocation lines over time. We discuss the issues of scaling the code to tens of thousands of processors, and present early scaling results of the code run on a prototype of the BlueGene/L supercomputer being developed by IBM in partnership with the US DOE's ASC program.

  19. The antioxidant methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

    PubMed

    Li, Xiang; Wang, Zhi-Gang; Chen, Hou-He; Liu, Sheng-Gao

    2014-11-01

    The title compound, C18H28O3, was prepared by the reaction of 2,6-di-tert-butylphenol with methyl acrylate under basic conditions using dimethyl sulfoxide as the promoter. The structure of this antioxidant indicates significant strain between the ortho tert-butyl substituents and the phenolic OH group. In spite of the steric crowding of the OH group, it participates in intermolecular hydrogen bonding with the ester carbonyl O atom. PMID:25370105

  20. [Adalberto Pazzini and the origins of the Istituto di Storia della Medicina].

    PubMed

    Conforti, Maria

    2006-01-01

    The first part of the paper deals with the Italian tradition of medical history in the 1930s, when Adalberto Pazzini became the most successful medical historian in Italy. Its second part deals with the founding and renovation (1938 and 1954 respectively) of the Istituto di Storia della Medicina at Rome University, with a description of the innovative--and largely utopian--planning of the Library and of the Museum and didactic collections by Pazzini.

  1. Strength and nature of hydrogen bonding interactions in mono- and di-hydrated formamide complexes.

    PubMed

    Angelina, Emilio L; Peruchena, Nélida M

    2011-05-12

    In this work, mono- and di-hydrated complexes of the formamide were studied. The calculations were performed at the MP2/6-311++G(d,p) level of approximation. The atoms in molecules theory (AIM), based on the topological properties of the electronic density distribution, was used to characterize the different types of bonds. The analysis of the hydrogen bonds (H-bonds) in the most stable mono- and di-hydrated formamide complexes shows a mutual reinforcement of the interactions, and some of these complexes can be considered as "bifunctional hydrogen bonding hydration complexes". In addition, we analyzed how the strength and the nature of the interactions, in mono-hydrated complexes, are modified by the presence of a second water molecule in di-hydrated formamide complexes. Structural changes, cooperativity, and electron density redistributions demonstrate that the H-bonds are stronger in the di-hydrated complexes than in the corresponding mono-hydrated complexes, wherein the σ- and π-electron delocalization were found. To explain the nature of such interactions, we carried out the atoms in molecules theory in conjunction with reduced variational space self-consistent field (RVS) decomposition analysis. On the basis of the local Virial theorem, the characteristics of the local electron energy density components at the bond critical points (BCPs) (the 1/4∇ (2)ρ(b) component of electron energy density and the kinetic energy density) were analyzed. These parameters were used in conjunction with the electron density and the Laplacian of the electron density to analyze the characteristics of the interactions. The analysis of the interaction energy components for the systems considered indicates that the strengthening of the hydrogen bonds is manifested by an increased contribution of the electrostatic energy component represented by the kinetic energy density at the BCP. PMID:21506592

  2. DiPerna-Lions Flow for Relativistic Particles in an Electromagnetic Field

    NASA Astrophysics Data System (ADS)

    Jabin, P.-E.; Masmoudi, N.

    2015-09-01

    We show the existence and uniqueness of a DiPerna-Lions flow for relativistic particles subject to a Lorentz force in an electromagnetic field. The electric and magnetic fields solve the linear Maxwell system in the vacuum but for singular initial conditions which are only in the physical energy space. As the corresponding force field is only in L 2, we have to perform a careful analysis of the cancellations over a trajectory.

  3. Manufacture of Fior di Latte cheese by incorporation of probiotic lactobacilli.

    PubMed

    Minervini, F; Siragusa, S; Faccia, M; Dal Bello, F; Gobbetti, M; De Angelis, M

    2012-02-01

    This work aimed to select heat-resistant probiotic lactobacilli to be added to Fior di Latte (high-moisture cow milk Mozzarella) cheese. First, 18 probiotic strains belonging to Lactobacillus casei, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri were screened. Resistance to heating (65 or 55°C for 10 min) varied markedly between strains. Adaptation at 42°C for 10 min increased the heat resistance at 55°C for 10 min of all probiotic lactobacilli. Heat-adapted L. delbrueckii ssp. bulgaricus SP5 (decimal reduction time at 55°C of 227.4 min) and L. paracasei BGP1 (decimal reduction time at 55°C of 40.8 min) showed the highest survival under heat conditions that mimicked the stretching of the curd and were used for the manufacture of Fior di Latte cheese. Two technology options were chosen: chemical (addition of lactic acid to milk) or biological (Streptococcus thermophilus as starter culture) acidification with or without addition of probiotics. As determined by random amplified polymorphic DNA-PCR and 16S rRNA gene analyses, the cell density of L. delbrueckii ssp. bulgaricus SP5 and L. paracasei BGP1 in chemically or biologically acidified Fior di Latte cheese was approximately 8.0 log(10)cfu/g. Microbiological, compositional, biochemical, and sensory analyses (panel test by 30 untrained judges) showed that the use of L. delbrueckii ssp. bulgaricus SP5 and L. paracasei BGP1 enhanced flavor formation and shelf-life of Fior di Latte cheeses.

  4. The antioxidant methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

    PubMed

    Li, Xiang; Wang, Zhi-Gang; Chen, Hou-He; Liu, Sheng-Gao

    2014-11-01

    The title compound, C18H28O3, was prepared by the reaction of 2,6-di-tert-butylphenol with methyl acrylate under basic conditions using dimethyl sulfoxide as the promoter. The structure of this antioxidant indicates significant strain between the ortho tert-butyl substituents and the phenolic OH group. In spite of the steric crowding of the OH group, it participates in intermolecular hydrogen bonding with the ester carbonyl O atom.

  5. ParaDiS on Blue Gene/L: stepping up to the challenge

    SciTech Connect

    Hommes, G; Arsenlis, A; Bulatov, V; Cai, W; Cook, R; Hiratani, M; Oppestrup, T; Rhee, M; Tang, M

    2006-06-09

    This paper reports on the efforts to enable fully scalable simulations of Dislocation Line Dynamics (DLD) for direct calculations of strength of crystalline materials. DLD simulations are challenging and do not lend themselves naturally to parallel computing. Through a combinations of novel physical approaches, mathematical algorithms and computational science developments, a new DLD code ParaDiS is shown to take meaningful advantage of BG/L and, by doing so, to enable discovery class science by computation.

  6. Strength and nature of hydrogen bonding interactions in mono- and di-hydrated formamide complexes.

    PubMed

    Angelina, Emilio L; Peruchena, Nélida M

    2011-05-12

    In this work, mono- and di-hydrated complexes of the formamide were studied. The calculations were performed at the MP2/6-311++G(d,p) level of approximation. The atoms in molecules theory (AIM), based on the topological properties of the electronic density distribution, was used to characterize the different types of bonds. The analysis of the hydrogen bonds (H-bonds) in the most stable mono- and di-hydrated formamide complexes shows a mutual reinforcement of the interactions, and some of these complexes can be considered as "bifunctional hydrogen bonding hydration complexes". In addition, we analyzed how the strength and the nature of the interactions, in mono-hydrated complexes, are modified by the presence of a second water molecule in di-hydrated formamide complexes. Structural changes, cooperativity, and electron density redistributions demonstrate that the H-bonds are stronger in the di-hydrated complexes than in the corresponding mono-hydrated complexes, wherein the σ- and π-electron delocalization were found. To explain the nature of such interactions, we carried out the atoms in molecules theory in conjunction with reduced variational space self-consistent field (RVS) decomposition analysis. On the basis of the local Virial theorem, the characteristics of the local electron energy density components at the bond critical points (BCPs) (the 1/4∇ (2)ρ(b) component of electron energy density and the kinetic energy density) were analyzed. These parameters were used in conjunction with the electron density and the Laplacian of the electron density to analyze the characteristics of the interactions. The analysis of the interaction energy components for the systems considered indicates that the strengthening of the hydrogen bonds is manifested by an increased contribution of the electrostatic energy component represented by the kinetic energy density at the BCP.

  7. Development and evaluation of systems for controlling parallel high di/dt thyratrons

    SciTech Connect

    Litton. A.; McDuff, G.

    1982-01-01

    Increasing numbers of high power, high repetition rate applications dictate the use or thyratrons in multiple of hard parallel configurations to achieve the required rate of current rise, di/dt. This in turn demands the development of systems to control parallel thyratron commutation with nanosecond accuracy. Such systems must be capable of real-time, fully-automated control in multi-kilohertz applications while still remaining cost effective. This paper describes the evolution of such a control methodology and system.

  8. USSAERO version D computer program development using ANSI standard FORTRAN 77 and DI-3000 graphics

    NASA Technical Reports Server (NTRS)

    Wiese, M. R.

    1986-01-01

    The D version of the Unified Subsonic Supersonic Aerodynamic Analysis (USSAERO) program is the result of numerous modifications and enhancements to the B01 version. These changes include conversion to ANSI standard FORTRAN 77; use of the DI-3000 graphics package; removal of the overlay structure; a revised input format; the addition of an input data analysis routine; and increasing the number of aeronautical components allowed.

  9. Mono-, di-, and tri- tert-butyl ethers of glycerol . A molecular spectroscopic study

    NASA Astrophysics Data System (ADS)

    Jamróz, Małgorzata E.; Jarosz, Małgorzata; Witowska-Jarosz, Janina; Bednarek, Elżbieta; Tęcza, Witold; Jamróz, Michał H.; Dobrowolski, Jan Cz.; Kijeński, Jacek

    2007-07-01

    MS, NMR, IR and Raman molecular spectroscopy techniques were applied to characterize 3- tert-butoxy-propane-1,2-diol, 1,3-di- tert-butoxy-propan-2-ol, and 1,2,3-tri- tert-butoxy-propane. These ethers are the main products of glycerol etherification reaction and are excellent oxygen additives for diesel fuel. Computational DFT/ B3LYP/6-31G ** studies were performed to support and rationalize both vibrational spectroscopy analysis and the isomer ratio.

  10. High-resolution enabled 12-plex DiLeu isobaric tags for quantitative proteomics.

    PubMed

    Frost, Dustin C; Greer, Tyler; Li, Lingjun

    2015-02-01

    Multiplex isobaric tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ)) are a valuable tool for high-throughput mass spectrometry based quantitative proteomics. We have developed our own multiplex isobaric tags, DiLeu, that feature quantitative performance on par with commercial offerings but can be readily synthesized in-house as a cost-effective alternative. In this work, we achieve a 3-fold increase in the multiplexing capacity of the DiLeu reagent without increasing structural complexity by exploiting mass defects that arise from selective incorporation of (13)C, (15)N, and (2)H stable isotopes in the reporter group. The inclusion of eight new reporter isotopologues that differ in mass from the existing four reporters by intervals of 6 mDa yields a 12-plex isobaric set that preserves the synthetic simplicity and quantitative performance of the original implementation. We show that the new reporter variants can be baseline-resolved in high-resolution higher-energy C-trap dissociation (HCD) spectra, and we demonstrate accurate 12-plex quantitation of a DiLeu-labeled Saccharomyces cerevisiae lysate digest via high-resolution nano liquid chromatography-tandem mass spectrometry (nanoLC-MS(2)) analysis on an Orbitrap Elite mass spectrometer. PMID:25405479

  11. High-Resolution Enabled 12-Plex DiLeu Isobaric Tags for Quantitative Proteomics

    PubMed Central

    2015-01-01

    Multiplex isobaric tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ)) are a valuable tool for high-throughput mass spectrometry based quantitative proteomics. We have developed our own multiplex isobaric tags, DiLeu, that feature quantitative performance on par with commercial offerings but can be readily synthesized in-house as a cost-effective alternative. In this work, we achieve a 3-fold increase in the multiplexing capacity of the DiLeu reagent without increasing structural complexity by exploiting mass defects that arise from selective incorporation of 13C, 15N, and 2H stable isotopes in the reporter group. The inclusion of eight new reporter isotopologues that differ in mass from the existing four reporters by intervals of 6 mDa yields a 12-plex isobaric set that preserves the synthetic simplicity and quantitative performance of the original implementation. We show that the new reporter variants can be baseline-resolved in high-resolution higher-energy C-trap dissociation (HCD) spectra, and we demonstrate accurate 12-plex quantitation of a DiLeu-labeled Saccharomyces cerevisiae lysate digest via high-resolution nano liquid chromatography–tandem mass spectrometry (nanoLC–MS2) analysis on an Orbitrap Elite mass spectrometer. PMID:25405479

  12. Biodegradation of Di-n-Butyl Phthalate by a Newly Isolated Halotolerant Sphingobium sp.

    PubMed Central

    Jin, Decai; Kong, Xiao; Cui, Bingjian; Bai, Zhihui; Zhang, Hongxun

    2013-01-01

    A Gram-negative strain (TJ) capable of growing aerobically on mixed phthalate esters (PAEs) as the sole carbon and energy source was isolated from the Haihe estuary, Tianjin, China. It was identified as belonging to the Sphingobium genus on the basis of morphological and physiological characteristics and 16S rRNA and gyrb gene sequencing. The batch tests for biodegradation of di-n-butyl phthalate (DBP) by the Sphingobium sp. TJ showed that the optimum conditions were 30 °C, pH 7.0, and the absence of NaCl. Stain TJ could tolerate up to 4% NaCl in minimal salt medium supplemented with DBP, although the DBP degradation rates slowed as NaCl concentration increased. In addition, substrate tests showed that strain TJ could utilize shorter side-chained PAEs, such as dimethyl phthalate and diethyl phthalate, but could not metabolize long-chained PAEs, such as di-n-octyl phthalate, diisooctyl phthalate, and di-(2-ethyl-hexyl) phthalate. To our knowledge, this is the first report on the biodegradation characteristics of DBP by a member of the Sphingobium genus. PMID:24336064

  13. Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.

    PubMed

    Jonas, Kristina; Edwards, Adrianne N; Ahmad, Irfan; Romeo, Tony; Römling, Ute; Melefors, Ojar

    2010-02-01

    Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.

  14. Automatic mechanism generation for pyrolysis of di-tert-butyl sulfide.

    PubMed

    Class, Caleb A; Liu, Mengjie; Vandeputte, Aäron G; Green, William H

    2016-08-01

    The automated Reaction Mechanism Generator (RMG), using rate parameters derived from ab initio CCSD(T) calculations, is used to build reaction networks for the thermal decomposition of di-tert-butyl sulfide. Simulation results were compared with data from pyrolysis experiments with and without the addition of a cyclohexene inhibitor. Purely free-radical chemistry did not properly explain the reactivity of di-tert-butyl sulfide, as the previous experimental work showed that the sulfide decomposed via first-order kinetics in the presence and absence of the radical inhibitor. The concerted unimolecular decomposition of di-tert-butyl sulfide to form isobutene and tert-butyl thiol was found to be a key reaction in both cases, as it explained the first-order sulfide decomposition. The computer-generated kinetic model predictions quantitatively match most of the experimental data, but the model is apparently missing pathways for radical-induced decomposition of thiols to form elemental sulfur. Cyclohexene has a significant effect on the composition of the radical pool, and this led to dramatic changes in the resulting product distribution. PMID:27431650

  15. Ab-initio study of germanium di-interstitial using a hybrid functional (HSE)

    NASA Astrophysics Data System (ADS)

    Igumbor, E.; Ouma, C. N. M.; Webb, G.; Meyer, W. E.

    2016-01-01

    In this work, we present ab-initio calculation results of Ge di-interstitials (I2(Ge)) in the framework of the density functional theory (DFT) using the Heyd, Scuseria, and Ernzerhof (HSE) hybrid functional. The formation energy, transition levels and minimum energy configurations were obtained for I2(Ge) -2, -1, 0, +1 and +2 charge states. The calculated formation energies show that for all charge states of I2(Ge), the double tetrahedral (T) configuration formed the most stable defect with a binding energy of 1.24 eV in the neutral state. We found the (+2/+1) charge state transition level for the T lying below the conduction band minimum and (+2/+1) for the split[110]-tetrahedral configuration lying deep at 0.41 eV above the valence band maximum. The di-interstitials in Ge exhibited the properties of both shallow and deep donor levels at (+2/+1) within the band gap and depending on the configurations. I2(Ge) gave rise to negative-U, with effective-U values of -0.61 and -1.6 eV in different configurations. We have compared our results with calculations of di-interstitials in silicon and available experimental data.

  16. Novel mono-, di-, and trimethylornithine membrane lipids in northern wetland planctomycetes.

    PubMed

    Moore, Eli K; Hopmans, Ellen C; Rijpstra, W Irene C; Villanueva, Laura; Dedysh, Svetlana N; Kulichevskaya, Irina S; Wienk, Hans; Schoutsen, Frans; Sinninghe Damsté, Jaap S

    2013-11-01

    Northern peatlands represent a significant global carbon store and commonly originate from Sphagnum moss-dominated wetlands. These ombrotrophic ecosystems are rain fed, resulting in nutrient-poor, acidic conditions. Members of the bacterial phylum Planctomycetes are highly abundant and appear to play an important role in the decomposition of Sphagnum-derived litter in these ecosystems. High-performance liquid chromatography coupled to high-resolution accurate-mass mass spectrometry (HPLC-HRAM/MS) analysis of lipid extracts of four isolated planctomycetes from wetlands of European north Russia revealed novel ornithine membrane lipids (OLs) that are mono-, di-, and trimethylated at the ε-nitrogen position of the ornithine head group. Nuclear magnetic resonance (NMR) analysis of the isolated trimethylornithine lipid confirmed the structural identification. Similar fatty acid distributions between mono-, di-, and trimethylornithine lipids suggest that the three lipid classes are biosynthetically linked, as in the sequential methylation of the terminal nitrogen in phosphatidylethanolamine to produce phosphatidylcholine. The mono-, di-, and trimethylornithine lipids described here represent the first report of methylation of the ornithine head groups in biological membranes. Various bacteria are known to produce OLs under phosphorus limitation or fatty-acid-hydroxylated OLs under thermal or acid stress. The sequential methylation of OLs, leading to a charged choline-like moiety in the trimethylornithine lipid head group, may be an adaptation to provide membrane stability under acidic conditions without the use of scarce phosphate in nutrient-poor ombrotrophic wetlands.

  17. Characterization of novel di- and tricarboxylic acids in fine tropical aerosols.

    PubMed

    Zdráhal, Z; Vermeylen, R; Claeys, M; Maenhaut, W; Guyon, P; Artaxo, P

    2001-04-01

    Three unknown di- and tricarboxylic acids were characterized in the fine size fraction of aerosols which were collected during the wet season in the Amazon basin (Rondonia, Brazil). For the structural characterization of the methyl esters of these unknown compounds, mass spectrometry with electron ionization (EI) and tandem mass spectral techniques combined with gas chromatographic (GC) separation were employed. Fragment and parent ion spectra were recorded during elution of the GC peaks by linked scanning of the B and E sectors in combination with high-energy collision-induced dissociation. The fragmentation patterns of significant ions in the first-order EI spectra were also obtained for nonanedioic acid, which was examined as a model compound. The compounds were tentatively identified as 4-acetyloxyheptanedioic acid and cis and trans isomers of 5-hexene-1,1,6-tricarboxylic acid. Since there were indications of biomass burning during the aerosol sampling the di- and tricarboxylic acids characterized in the present work could be markers for biomass burning. Furthermore, the characterization of di- and tricarboxylic acids in the fine size fraction of atmospheric aerosols may be important for assessing the effects of organic aerosols in cloud formation.

  18. Hooked on the nicotine addiction thesis: a response to DiFranza

    PubMed Central

    2013-01-01

    DiFranza’s rebuttal to our critique of the “Hooked on Nicotine” research program misconstrues our arguments beyond recognition. The grossest misrepresentation of our critique by DiFranza is that we devise (by thwarting science) to rescue “the conventional wisdom” of the “threshold model of nicotine addiction.” In fact, the difference between our positions lies elsewhere: We believe that nicotine is not an addictive drug and that its contribution to the smoking habit is secondary; DiFranza believes that nicotine is so powerfully addictive that novice smokers can lose autonomy over their smoking behavior after one cigarette or even following a single puff. Our review aimed to critically examine the empirical basis of this extreme version of the nicotine “addiction” model. In this brief commentary we illustrate how the commitment to the nicotine “addiction” theory has biased the methodology and the interpretation of the data in “Hooked on Nicotine” research program. PMID:24246023

  19. Understanding of pictograms from the United States Pharmacopeia Dispensing Information (USP-DI) among elderly Brazilians

    PubMed Central

    Barros, Izadora MC; Alcântara, Thaciana S; Mesquita, Alessandra R; Bispo, Monica L; Rocha, Chiara E; Moreira, Vagner Porto; Lyra Junior, Divaldo P

    2014-01-01

    Objective To assess the understanding and cultural acceptability of the United States Pharmacopeia Dispensing Information (USP-DI) in a group of elderly Brazilians. Methods The study participants were individuals between 60 and 90 years old, of both sexes, with different levels of education and income. Fifteen of 81 pictograms from the USP-DI were presented to the elderly subjects, individually, without subtitles and in random order, so that the participants’ understanding of the pictograms could be evaluated. Results The study included 116 participants. Only one of the selected pictograms reached the comprehension criterion established by the International Organization for Standardization 3864. With regard to the relationship between understanding and sociodemographic characteristics, age, wage income, and level of education were all found to be significantly associated with participants’ understanding of some of the pictograms. Conclusion Most of the USP-DI pictograms evaluated were not well understood by the elderly Brazilians. This finding indicates that such pictograms need to be culturally adapted for the Brazilian context if they are to serve their purpose effectively in this country. PMID:25378914

  20. C-di-GMP Synthesis: Structural Aspects of Evolution, Catalysis and Regulation.

    PubMed

    Schirmer, Tilman

    2016-09-25

    Cellular levels of the second messenger cyclic di-guanosine monophosphate (c-di-GMP) are determined by the antagonistic activities of diguanylate cyclases and specific phosphodiesterases. In a given bacterial organism, there are often multiple variants of the two enzymes, which are tightly regulated by a variety of external and internal cues due to the presence of specialized sensory or regulatory domains. Dependent on the second messenger level, specific c-di-GMP receptors then control fundamental cellular processes, such as bacterial life style, biofilm formation, and cell cycle control. Here, I review the large body of data on structure-function relationships in diguanylate cyclases. Although the catalytic GGDEF domain is related to the respective domain of adenylate cyclases, the catalyzed intermolecular condensation reaction of two GTP molecules requires the formation of a competent GGDEF dimer with the two substrate molecules juxtaposed. This prerequisite appears to constitute the basis for GGDEF regulation with signal-induced changes within the homotypic dimer of the input domain (PAS, GAF, HAMP, etc.), which are structurally coupled with the arrangement of the GGDEF domains via a rigid coiled-coil linker. Alternatively, phosphorylation of a Rec input domain can drive GGDEF dimerization. Both mechanisms allow modular combination of input and output function that appears advantageous for evolution and rationalizes the striking similarities in domain architecture found in diguanylate cyclases and histidine kinases. PMID:27498163

  1. Novel Mono-, Di-, and Trimethylornithine Membrane Lipids in Northern Wetland Planctomycetes

    PubMed Central

    Hopmans, Ellen C.; Rijpstra, W. Irene C.; Villanueva, Laura; Dedysh, Svetlana N.; Kulichevskaya, Irina S.; Wienk, Hans; Schoutsen, Frans; Sinninghe Damsté, Jaap S.

    2013-01-01

    Northern peatlands represent a significant global carbon store and commonly originate from Sphagnum moss-dominated wetlands. These ombrotrophic ecosystems are rain fed, resulting in nutrient-poor, acidic conditions. Members of the bacterial phylum Planctomycetes are highly abundant and appear to play an important role in the decomposition of Sphagnum-derived litter in these ecosystems. High-performance liquid chromatography coupled to high-resolution accurate-mass mass spectrometry (HPLC-HRAM/MS) analysis of lipid extracts of four isolated planctomycetes from wetlands of European north Russia revealed novel ornithine membrane lipids (OLs) that are mono-, di-, and trimethylated at the ε-nitrogen position of the ornithine head group. Nuclear magnetic resonance (NMR) analysis of the isolated trimethylornithine lipid confirmed the structural identification. Similar fatty acid distributions between mono-, di-, and trimethylornithine lipids suggest that the three lipid classes are biosynthetically linked, as in the sequential methylation of the terminal nitrogen in phosphatidylethanolamine to produce phosphatidylcholine. The mono-, di-, and trimethylornithine lipids described here represent the first report of methylation of the ornithine head groups in biological membranes. Various bacteria are known to produce OLs under phosphorus limitation or fatty-acid-hydroxylated OLs under thermal or acid stress. The sequential methylation of OLs, leading to a charged choline-like moiety in the trimethylornithine lipid head group, may be an adaptation to provide membrane stability under acidic conditions without the use of scarce phosphate in nutrient-poor ombrotrophic wetlands. PMID:23995937

  2. Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

    NASA Astrophysics Data System (ADS)

    Kohnen, Math E. l.; Sinninghe Damsté, Jaap S.; Kock-van Dalen, A. c.; Jan, W. De Leeuw

    1991-05-01

    Three types of sulphur-rich high-molecular-weight material in the alkylsulphide, the polar, and the asphaltene fractions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised using Raney Ni and were treated with MeLi/MeI, a chemical degradation method which cleaves selectively and quantitatively di- or polysulphide linkages. The products formed were characterised by gas chromatography-mass spectrometry. Raney Ni desulphurisation revealed that these S-rich macromolecules are in substantial part composed of sulphur-linked biomarkers with linear, branched, isoprenoid, steroid, hopanoid, and carotenoid carbon skeletons. MeLi/Mel treatment provided evidence that a major part of the total amount of macromolecularly bound biomarkers are linked via di- or polysulphide moieties to the macromolecular network. Since the di- or polysulphide linkages are attached at specific positions of the bound biomarkers it is proposed that they are formed by intermolecular incorporation reactions of HS x- into low-molecular-weight functionalised biological lipids during early diagenesis. The different properties (solubility and molecular weight) of the sulphur-rich macromolecules in the alkylsulphide, the resin, and the asphaltene fractions can be explained simply by differences in degree of sulphur cross-linking.

  3. Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking.

    PubMed

    Dubey, Badri N; Lori, Christian; Ozaki, Shogo; Fucile, Geoffrey; Plaza-Menacho, Ivan; Jenal, Urs; Schirmer, Tilman

    2016-09-01

    Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling. PMID:27652341

  4. C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth

    PubMed Central

    Chua, Song Lin; Sivakumar, Krishnakumar; Rybtke, Morten; Yuan, Mingjun; Andersen, Jens Bo; Nielsen, Thomas E.; Givskov, Michael; Tolker-Nielsen, Tim; Cao, Bin; Kjelleberg, Staffan; Yang, Liang

    2015-01-01

    Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO32–) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO32– further increased P. aeruginosa biofilm formation and resistance to TeO32–. P. aeruginosa ΔsadCΔsiaD and PAO1/plac-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO32– exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO32–. Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth. PMID:25992876

  5. C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth.

    PubMed

    Chua, Song Lin; Sivakumar, Krishnakumar; Rybtke, Morten; Yuan, Mingjun; Andersen, Jens Bo; Nielsen, Thomas E; Givskov, Michael; Tolker-Nielsen, Tim; Cao, Bin; Kjelleberg, Staffan; Yang, Liang

    2015-01-01

    Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO3(2-)) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO3(2-) further increased P. aeruginosa biofilm formation and resistance to TeO3(2-). P. aeruginosa ΔsadCΔsiaD and PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO3(2-) exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO3(2-). Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth.

  6. 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.

  7. Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking.

    PubMed

    Dubey, Badri N; Lori, Christian; Ozaki, Shogo; Fucile, Geoffrey; Plaza-Menacho, Ivan; Jenal, Urs; Schirmer, Tilman

    2016-09-01

    Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling.

  8. 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

  9. Elevated level of the second messenger c-di-GMP in Comamonas testosteroni enhances biofilm formation and biofilm-based biodegradation of 3-chloroaniline.

    PubMed

    Wu, Yichao; Ding, Yuanzhao; Cohen, Yehuda; Cao, Bin

    2015-02-01

    The bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous second messenger that determines bacterial lifestyle between the planktonic and biofilm modes of life. Although the role of c-di-GMP signaling in biofilm development and dispersal has been extensively studied, how c-di-GMP signaling influences environmental bioprocess activities such as biodegradation remains unexplored. To elucidate the impacts of elevating c-di-GMP level on environmental bioprocesses, we constructed a Comamonas testosteroni strain constitutively expressing a c-di-GMP synthase YedQ from Escherichia coli and examined its capability in biofilm formation and biodegradation of 3-chloroaniline (3-CA). The high c-di-GMP strain exhibited an increased binding to Congo red dye, a decreased motility, and an enhanced biofilm formation capability. In planktonic cultures, the strain with an elevated c-di-GMP concentration and the wild type could degrade 3-CA comparably well. However, under batch growth conditions with a high surface to volume ratio, an elevated c-di-GMP concentration in C. testosteroni significantly increased the contribution of biofilms in 3-CA biodegradation. In continuous submerged biofilm reactors, C. testosteroni with an elevated c-di-GMP level exhibited an enhanced 3-CA biodegradation and a decreased cell detachment rate. Taken together, this study provides a novel strategy to enhance biofilm-based biodegradation of toxic xenobiotic compounds through manipulating bacterial c-di-GMP signaling.

  10. DiOC6 staining reveals organelle structure and dynamics in living yeast cells.

    PubMed

    Koning, A J; Lum, P Y; Williams, J M; Wright, R

    1993-01-01

    When present at low concentrations, the fluorescent lipophilic dye, DiOC6, stains mitochondria in living yeast cells [Pringle et al.: Methods in Cell Biol. 31:357-435, 1989; Weisman et al.: Proc. Natl. Acad. Sci. U.S.A. 87:1076-1080, 1990]. However, we found that the nuclear envelope and endoplasmic reticulum were specifically stained if the dye concentration was increased or if certain respiratory-deficient yeast strains were examined. The quality of nuclear envelope staining with DiOC6 was sufficiently sensitive to reveal alterations in the nuclear envelope known as karmellae. These membranes were previously apparent only by electron microscopy. At the high dye concentrations required to stain the nuclear envelope, wild-type cells could no longer grow on non-fermentable carbon sources. In spite of this effect on mitochondrial function, the presence of high dye concentration did not adversely affect cell viability or general growth characteristics when strains were grown under standard conditions on glucose. Consequently, time-lapse confocal microscopy was used to examine organelle dynamics in living yeast cells stained with DiOC6. These in vivo observations correlated very well with previous electron microscopic studies, including analyses of mitochondria, karmellae, and mitosis. For example, cycles of mitochondrial fusion and division, as well as the changes in nuclear shape and position that occur during mitosis, were readily imaged in time-lapse studies of living DiOC6-stained cells. This technique also revealed new aspects of nuclear disposition and interactions with other organelles. For example, the nucleus and vacuole appeared to form a structurally coupled unit that could undergo coordinated movements. Furthermore, unlike the general view that nuclear movements occur only in association with division, the nucleus/vacuole underwent dramatic migrations around the cell periphery as cells exited from stationary phase. In addition to the large migrations or

  11. Calibrazioni a terra e prestazioni in volo di spettrometri ad immagine nel visibile e nel vicino infrarosso per l'esplorazione planetaria

    NASA Astrophysics Data System (ADS)

    Filacchione, Gianrico

    2006-10-01

    Nel corso dell’ultimo decennio l’esplorazione planetaria ha potuto beneficiare dei dati prodotti dagli spettrometri ad immagine: grazie a questa nuova classe di strumenti, realizzati per l’osservazione in remoto di superfici ed atmosfere planetarie, è possibile acquisire dati iperspettrali con elevati poteri risolutivi spaziali e spettrali. Il principale vantaggio offerto dagli spettrometri ad immagine, rispetto alle camere ed agli spettrometri puntuali, è rappresentato dalla capacità di misurare, identificare e mappare le unità composizionali delle superfici planetarie; queste informazioni permettono di investigare sia l’evoluzione geochimica delle superfici sia la dinamica e la composizione delle atmosfere. Sebbene i primi spettrometri ad immagine siano stati francesi (Phobos/ISM, Imaging Spectrometer for Mars) e statunitensi (Galileo/NIMS, Near Infrared Mapping Spectrometer), il nostro paese nel corso degli ultimi anni è stato in grado di proporre alla com unità spaziale internazionale degli strumenti dalle elevate prestazioni che sono stati infatti accettati come payload scientifici su diverse missioni interplanetarie: dai canali visibili di VIMS (Visual and Infrared Mapping Spectrometer) su Cassini (Nasa, JPL, ESA, ASI) e di OMEGA (Observatoire pour la Minéralogie, l’Eau, les Glacies et l’Activitè de Mars) su MarsExpress (ESA) ai due VIRTIS (Visible and Infrared Thermal Imaging Spectrometer) su Rosetta (ESA) e VenusExpress (ESA) fino a VIR-MS (Visible and Infrared Mapping Spectrometer) su Dawn (Nasa). In questo momento inoltre altri due spettrometri sono in avanzata fase di studio: JIRAM (Jovian InfraRed Auroral Mapper) su Juno (missione New Discovery Nasa) e VIHI (Visible and Infrared Hyperspectral Imager) integrato nel payload italiano di remote sensing SIMBIO-SYS di BepiColombo (missione cornerstone ESA). La realizzazione di uno spettrometro ad immagini da utilizzare su una missione interplanetaria richiede un’accurata analisi in fase

  12. 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.

  13. Analysis of the selective advantage conferred by a C-E1 fusion protein synthesized by rubella virus DI RNAs

    SciTech Connect

    Claus, Claudia; Tzeng, W.-P.; Liebert, Uwe Gerd; Frey, Teryl K.

    2007-12-05

    During serial passaging of rubella virus (RUB) in cell culture, the dominant species of defective-interfering RNA (DI) generated contains an in-frame deletion between the capsid protein (C) gene and E1 glycoprotein gene resulting in production of a C-E1 fusion protein that is necessary for the maintenance of the DI [Tzeng, W.P., Frey, T.K. (2006). C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage. Virology 356 198-207.]. A BHK cell line stably expressing the RUB structural proteins was established which was used to package DIs into virus particles following transfection with in vitro transcripts from DI infectious cDNA constructs. Packaging of a DI encoding an in-frame C-GFP-E1 reporter fusion protein corresponding to the C-E1 fusion protein expressed in a native DI was only marginally more efficient than packaging of a DI encoding GFP, indicating that the C-E1 fusion protein did not function by enhancing packaging. However, infection with the DI encoding the C-GFP-E1 fusion protein (in the absence of wt RUB helper virus) resulted in formation of clusters of GFP-positive cells and the percentage of GFP-positive cells in the culture following infection remained relatively constant. In contrast, a DI encoding GFP did not form GFP-positive clusters and the percentage of GFP-positive cells declined by roughly half from 2 to 4 days post-infection. Cluster formation and sustaining the percentage of infected (GFP-positive) cells required the C part of the fusion protein, including the downstream but not the upstream of two arginine clusters (both of which are associated with RNA binding and association with mitochondrial p32 protein) and the E1 part through the transmembrane sequence, but not the C-terminal cytoplasmic tail. Among a collection of mutant DI constructs, cluster formation and sustaining infected cell percentage correlated with maintenance during serial passage with wt RUB. We hypothesize that cluster formation and

  14. Crystal structure of di­chlorido­bis­(N,N′-di­methyl­thio­urea-κS)mercury(II)

    PubMed Central

    Shaheen, Muhammad Ashraf; Munawar, Aisha; Sadaf, Haseeba; Tahir, Muhammad Nawaz; Isab, Anvarhusein A.; Ahmad, Saeed

    2015-01-01

    The mol­ecular structure of the title compound, [HgCl2(C3H8N2S)2], has point group symmetry 2, with the twofold rotation axis passing through the HgII atom. The latter is coordinated by two Cl atoms and two N,N′-di­methyl­thio­urea (Dmtu) ligands through their S atoms, defining a distorted tetra­hedral coordination sphere with bond angles in the range 102.47 (4)–118.32 (4)°. Intra- and inter­molecular hydrogen bonds of the type N—H⋯Cl with S(6) and R 2 2(12) ring motifs are present. The inter­molecular contacts make up polymeric chains extending parallel to [101]. PMID:26396848

  15. Study on the interaction of Co (III) DiAmsar with serum albumins: Spectroscopic and molecular docking methods

    NASA Astrophysics Data System (ADS)

    Farahani, Bahman Vasheghani; Bardajee, Ghasem Rezanejade; Rajabi, Farzaneh Hosseinpour; Hooshyar, Zari

    2015-01-01

    This study was designed to examine the interaction of cobalt-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (Co(III) DiAmsar) as a hexadentate ligand with human serum albumin (HSA) and bovine serum albumin (BSA) under physiological conditions in Tris-HCl buffer solution at pH 7.4. To this aim, at first, Co (III) DiAmsar was synthesized and characterized by nuclear magnetic resonance (NMR), and mass spectroscopy and then its interaction with HSA and BSA was investigated by means of various spectroscopic methods (Fourier transform infrared (FT-IR), UV-visible (UV-vis), fluorescence, and cyclic voltammetry (CV)) and molecular docking technique. The results of fluorescence titration revealed that the Co (III) DiAmsar strongly quench the intrinsic fluorescence of HSA and BSA through a static quenching procedure. Binding constants (Ka) and the number of binding sites (n ∼ 1) were calculated using Stern-Volmer equations. The ΔG parameters at different temperatures were calculated. Subsequently, the values of ΔH and ΔS were also calculated, which revealed that the van der Waals and hydrogen bonding interaction splay a major role in Co (III) DiAmsar-HSA and Co (III) DiAmsar-BSA associations. The distance r between donor (HSA and BSA) and acceptor (Co (III) DiAmsar) was obtained according to fluorescence resonance energy transfer. The data obtained by the molecular modeling study revealed the surrounding residues of HSA and BSA around Co (III) DiAmsar.

  16. Development and characterization of novel 8-plex DiLeu isobaric labels for quantitative proteomics and peptidomics

    PubMed Central

    Frost, Dustin C.; Greer, Tyler; Xiang, Feng; Liang, Zhidan; Li, Lingjun

    2015-01-01

    Rationale Relative quantification of proteins via their enzymatically digested peptide products determines disease biomarker candidate lists in discovery studies. Isobaric label-based strategies using TMT and iTRAQ allow for up to 10 samples to be multiplexed in one experiment, but their expense limits their use. The demand for cost-effective tagging reagents capable of multiplexing many samples led us to develop an 8-plex version of our isobaric labeling reagent, DiLeu. Methods The original 4-plex DiLeu reagent was extended to an 8-plex set by coupling isotopic variants of dimethylated leucine to an alanine balance group designed to offset the increasing mass of the label’s reporter group. Tryptic peptides from a single protein digest, a protein mixture digest, and Saccharomyces cerevisiae lysate digest were labeled with 8-plex DiLeu and analyzed via nanoLC-MS2 on a Q-Exactive Orbitrap mass spectrometer. Characteristics of 8-plex DiLeu-labeled peptides, including quantitative accuracy and fragmentation, were examined. Results An 8-plex set of DiLeu reagents with 1 Da-spaced reporters was synthesized at a yield of 36%. The average cost to label eight 100 μg peptide samples was calculated to be approximately $15. Normalized collision energy tests on the Q-Exactive revealed that a higher-energy collisional dissociation value of 27 generated the optimum number of high-quality spectral matches. Relative quantification of DiLeu-labeled peptides yielded normalized median ratios accurate to within 12% of their expected values. Conclusions Cost-effective 8-plex DiLeu reagents can be synthesized and applied to relative peptide and protein quantification. These labels increase the multiplexing capacity of our previous 4-plex implementation without requiring high-resolution instrumentation to resolve reporter ion signals. PMID:25981542

  17. Low aquaporin-2 levels in polyuric DI +/+ severe mice with constitutively high cAMP-phosphodiesterase activity.

    PubMed

    Frøkiaer, J; Marples, D; Valtin, H; Morris, J F; Knepper, M A; Nielsen, S

    1999-02-01

    In the renal collecting duct, vasopressin acutely activates cAMP production, resulting in trafficking of aquaporin-2 water channels (AQP2) to the apical plasma membrane, thereby increasing water permeability. This acute response is modulated by long-term changes in AQP2 expression. Recently, a cAMP-responsive element has been identified in the AQP2 gene, raising the possibility that changes in cAMP levels may control AQP2 expression. To investigate this possibility, we determined AQP2 protein levels in a strain of mice, DI +/+ severe (DI), which have genetically high levels of cAMP-phosphodiesterase activity, and hence low cellular cAMP levels, and severe polyuria. Semiquantitative immunoblotting of membrane fractions prepared from whole kidneys revealed that AQP2 levels in DI mice were only 26 +/- 7% (+/-SE) of those in control mice (n = 10, P < 0.01). In addition, semiquantitative Northern blotting revealed a significantly lower AQP2 mRNA expression in kidneys from DI mice compared with control mice (43 +/- 6% vs. 100 +/- 10%; n = 6 in each group, P < 0.05). AQP3 levels were also reduced. The mice were polyuric and urine osmolalities were accordingly substantially lower in the DI mice than in controls (496 +/- 53 vs. 1,696 +/- 105 mosmol/kgH2O, respectively). Moreover, there was a linear correlation between urine osmolalities and AQP2 levels (P < 0.05). Immunoelectron microscopy confirmed the markedly lower expression of AQP2 in collecting duct principal cells in kidneys of DI mice and, furthermore, demonstrated that AQP2 was almost completely absent from the apical plasma membrane. Thus expression of AQP2 and AQP2 trafficking were severely impaired in DI mice. These results are consistent with the view that in vivo regulation of AQP2 expression by vasopressin is mediated by cAMP. PMID:9950948

  18. Cyclic di-GMP-mediated repression of swarming motility by Pseudomonas aeruginosa PA14 requires the MotAB stator.

    PubMed

    Kuchma, S L; Delalez, N J; Filkins, L M; Snavely, E A; Armitage, J P; O'Toole, G A

    2015-02-01

    The second messenger cyclic diguanylate (c-di-GMP) plays a critical role in the regulation of motility. In Pseudomonas aeruginosa PA14, c-di-GMP inversely controls biofilm formation and surface swarming motility, with high levels of this dinucleotide signal stimulating biofilm formation and repressing swarming. P. aeruginosa encodes two stator complexes, MotAB and MotCD, that participate in the function of its single polar flagellum. Here we show that the repression of swarming motility requires a functional MotAB stator complex. Mutating the motAB genes restores swarming motility to a strain with artificially elevated levels of c-di-GMP as well as stimulates swarming in the wild-type strain, while overexpression of MotA from a plasmid represses swarming motility. Using point mutations in MotA and the FliG rotor protein of the motor supports the conclusion that MotA-FliG interactions are critical for c-di-GMP-mediated swarming inhibition. Finally, we show that high c-di-GMP levels affect the localization of a green fluorescent protein (GFP)-MotD fusion, indicating a mechanism whereby this second messenger has an impact on MotCD function. We propose that when c-di-GMP level is high, the MotAB stator can displace MotCD from the motor, thereby affecting motor function. Our data suggest a newly identified means of c-di-GMP-mediated control of surface motility, perhaps conserved among Pseudomonas, Xanthomonas, and other organisms that encode two stator systems.

  19. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos....

  20. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6...-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92-343 and P-92-344) are subject...

  1. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos....

  2. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos....

  3. Synthesis, structural characterization, electronic spectroscopy, and microfluidic detection of Cu+2 and UO2+2 [di-tert-butyl-salphenazine] complexes†

    PubMed Central

    Maynard, B. A.; Brooks, J. C.; Hardy, E. E.; Easley, C. J.; Gorden, A. E. V.

    2015-01-01

    Metal templation by condensation of 2,3-diaminophenazine with 3,5-di-tert-butyl-2-hydroxybenzaldehyde around the metal centers [M = Cu(ii), and UO2(vi)] affords a new class of M[di-tert-butyl sal-phenazine] metal complexes. Reported here is the synthesis, single crystal X-ray structural characterization, electronic spectroscopy, and microfluidic detection of the formation of these M[di-tert-butyl sal-phenazine] complexes. PMID:25657039

  4. Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir

    PubMed Central

    Dimmock, Nigel J.; Dove, Brian K.; Meng, Bo; Scott, Paul D.; Taylor, Irene; Cheung, Linda; Hallis, Bassam; Marriott, Anthony C.; Carroll, Miles W.; Easton, Andrew J.

    2012-01-01

    The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. Defective interfering (DI) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 DI RNA in a cloned A/PR/8/34 virus; 244/PR8) has proved effective in preclinical studies in mice. The active principle is the DI RNA, and this is thought to interact with all influenza A viruses by inhibiting RNA virus synthesis and packaging of the cognate virion RNA into nascent DI virus particles. We have compared the ability of DI virus and oseltamivir to protect ferrets from intranasal 2009 pandemic influenza virus A/California/04/09 (A/Cal, H1N1). Ferrets were treated with a single 2 μg intranasal dose of 244 DI RNA delivered as 244/PR8 virus, or a total of 25 mg/kg body weight of oseltamivir given as 10 oral doses over 5 days. Both DI virus and oseltamivir reduced day 2 infectivity and the influx of cells into nasal fluids, and permitted the development of adaptive immunity. However DI virus, but not oseltamivir, significantly reduced weight loss, facilitated better weight gain, reduced respiratory disease, and reduced infectivity on days 4 and 6. 244 DI RNA was amplified by A/Cal by >25,000-fold, consistent with the amelioration of clinical disease. Treatment with DI virus did not delay clearance or cause persistence of infectious virus or DI RNA. Thus in this system DI virus was overall more effective than oseltamivir in combatting pandemic A/California/04/09. PMID:23041142

  5. Aerobic biodegradation of toluene-2,4-di(8:2 fluorotelomer urethane) and hexamethylene-1,6-di(8:2 fluorotelomer urethane) monomers in soils.

    PubMed

    Dasu, Kavitha; Lee, Linda S

    2016-02-01

    Aerobic soil biodegradation of toluene-2,4-di(8:2 fluorotelomer urethane) (FTU) and hexamethylene-1,6-di(8:2 fluorotelomer urethane) (HMU) in a forest soil and FTU in an agricultural silty clay loam soil was monitored for up to 6 months. Fluorotelomer alcohols were measured in headspace and parent monomers and all metabolites in soil extracts. Negligible degradation of FTU biodegradation occurred in the agricultural soil with 94 ± 15% recovered at day 180. However, in the forest soil, both FTU and HMU degradation was evident with significant losses of 24% (117 d) and 27% (180 day), respectively, and concomitant increases in the terminal metabolite, perfluorooctanoic acid (PFOA) concentrations were well above what could result from residual 8:2 FTOH. Kinetic modeling estimated half-lives for FTU (aromatic backbone) and HMU (aliphatic backbone) in the forest soil to be 3-5 months and 15.9-22.2 months, respectively. The addition of a structurally similar non-fluorinated FTU analog, toluene-2,4-dicarbamic acid diethyl ester (TDAEE) enhanced production of terminal end products from 8:2 FTOH degradation. However, there was no clear evidence that TDAEE enhanced cleavage of the urethane bond, thus TDAEE appeared to just serve as an additional carbon source. TDAEE's half-life was ∼ one week. A second addition of TDAEE appeared to retard subsequent degradation of FTU exemplifying the microbial dynamics and diversity impacting degradation of polyfluoroalkyl substances. Enhanced degradation of HMU was observed upon re-aeration indicating oxygen may have been limiting during some periods although degradation of intermediate metabolites to terminal metabolites was still occurring, albeit at slower rates.

  6. Aerobic biodegradation of toluene-2,4-di(8:2 fluorotelomer urethane) and hexamethylene-1,6-di(8:2 fluorotelomer urethane) monomers in soils.

    PubMed

    Dasu, Kavitha; Lee, Linda S

    2016-02-01

    Aerobic soil biodegradation of toluene-2,4-di(8:2 fluorotelomer urethane) (FTU) and hexamethylene-1,6-di(8:2 fluorotelomer urethane) (HMU) in a forest soil and FTU in an agricultural silty clay loam soil was monitored for up to 6 months. Fluorotelomer alcohols were measured in headspace and parent monomers and all metabolites in soil extracts. Negligible degradation of FTU biodegradation occurred in the agricultural soil with 94 ± 15% recovered at day 180. However, in the forest soil, both FTU and HMU degradation was evident with significant losses of 24% (117 d) and 27% (180 day), respectively, and concomitant increases in the terminal metabolite, perfluorooctanoic acid (PFOA) concentrations were well above what could result from residual 8:2 FTOH. Kinetic modeling estimated half-lives for FTU (aromatic backbone) and HMU (aliphatic backbone) in the forest soil to be 3-5 months and 15.9-22.2 months, respectively. The addition of a structurally similar non-fluorinated FTU analog, toluene-2,4-dicarbamic acid diethyl ester (TDAEE) enhanced production of terminal end products from 8:2 FTOH degradation. However, there was no clear evidence that TDAEE enhanced cleavage of the urethane bond, thus TDAEE appeared to just serve as an additional carbon source. TDAEE's half-life was ∼ one week. A second addition of TDAEE appeared to retard subsequent degradation of FTU exemplifying the microbial dynamics and diversity impacting degradation of polyfluoroalkyl substances. Enhanced degradation of HMU was observed upon re-aeration indicating oxygen may have been limiting during some periods although degradation of intermediate metabolites to terminal metabolites was still occurring, albeit at slower rates. PMID:26624955

  7. Thiazole orange-induced c-di-GMP quadruplex formation facilitates a simple fluorescent detection of this ubiquitous biofilm regulating molecule.

    PubMed

    Nakayama, Shizuka; Kelsey, Ilana; Wang, Jingxin; Roelofs, Kevin; Stefane, Bogdan; Luo, Yiling; Lee, Vincent T; Sintim, Herman O

    2011-04-01

    Recently, there has been an explosion of research activities in the cyclic dinucleotides field. Cyclic dinucleotides, such as c-di-GMP and c-di-AMP, have been shown to regulate bacterial virulence and biofilm formation. c-di-GMP can exist in different aggregate forms, and it has been demonstrated that the polymorphism of c-di-GMP is influenced by the nature of cation that is present in solution. In previous work, polymorphism of c-di-GMP could only be demonstrated at hundreds of micromolar concentrations of the dinucleotide, and it has been a matter of debate if polymorphism of c-di-GMP exists under in vivo conditions. In this Article, we demonstrate that c-di-GMP can form G-quadruplexes at low micromolar concentrations when aromatic molecules such as thiazole orange template the quadruplex formation. We then use this property of aromatic molecule-induced G-quadruplex formation of c-di-GMP to design a thiazole orange-based fluorescent detection of this important signaling molecule. We determine, using this thiazole orange assay on a crude bacterial cell lysate, that WspR D70E (a constitutively activated diguanylate cyclase) is functional in vivo when overexpressed in E. Coli . The intracellular concentration of c-di-GMP in an E. Coli cell that is overexpressed with WspR D70E is very high and can reach 2.92 mM.

  8. Di-Neutron Clustering and Deuteron-like Tensor Correlation in Nuclear Structure Focusing on 11Li

    NASA Astrophysics Data System (ADS)

    Ikeda, Kiyomi; Myo, Takayuki; Kato, Kiyoshi; Toki, Hiroshi

    11Li is a Borromean nucleus, where two out of three objects as 9Li + n and two neutrons independently do not form bound systems. Two neutrons should form a di-neutron cluster in the nuclear field generated by the 9Li core nucleus. We treat di-neutron clustering by solving the two neutron relative wave function precisely by using the bare nucleon-nucleon interaction so that the spatial clustering structure is obtained quantitatively within the whole 11Li nucleus. This di-neutron clustering is an essential dynamics to form the halo structure by making a compact di-neutron cluster, which distributes loosely around the 9Li core. This concept of di-neutron clustering should be clearly distinguished from the BCS pairing correlation, where no consideration of spatial clustering is made. The di-neutron clustering is a new concept and is a general phenomenon in neutron skin and neutron halo nuclei. This quantitative description of di-neutron clustering has made it necessary to consider another important deuteron-like tensor correlation, which is caused by strong tensor interaction in the nucleon-nucleon interaction. The tensor interaction originates from pion exchange and known to provide large attraction to form the 4He nucleus. The unique feature of the tensor correlation is to make highly correlated deuteron-like excitation, which interferes with shell model like structure in a unique way. This dynamical effect removes the magic number effect and makes easy the participation of the s-wave neutrons. Hence, there are pairing and deuteron-like tensor correlations in addition to the mean field structure in 9Li. The combined system of two additional neutrons with the correlated 9Li provides the halo phenomenon, in which the di-neutron clustering develops with the help of large s-wave component caused by the deuteron-like tensor correlation. These two effects, the di-neutron clustering and the deuteron-like tensor correlation, are quite new and essential to provide the halo

  9. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding.

    PubMed

    Ouyang, Songying; Song, Xianqiang; Wang, Yaya; Ru, Heng; Shaw, Neil; Jiang, Yan; Niu, Fengfeng; Zhu, Yanping; Qiu, Weicheng; Parvatiyar, Kislay; Li, Yang; Zhang, Rongguang; Cheng, Genhong; Liu, Zhi-Jie

    2012-06-29

    STING is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway. It contains an N-terminal transmembrane region and a cytosolic C-terminal domain (CTD). Here, we describe crystal structures of STING CTD alone and complexed with c-di-GMP in a unique binding mode. The strictly conserved aa 153-173 region was shown to be cytosolic and participated in dimerization via hydrophobic interactions. The STING CTD functions as a dimer and the dimerization was independent of posttranslational modifications. Binding of c-di-GMP enhanced interaction of a shorter construct of STING CTD (residues 139-344) with TBK1. This suggests an extra TBK1 binding site, other than serine 358. This study provides a glimpse into the unique architecture of STING and sheds light on the mechanism of c-di-GMP-mediated TBK1 signaling.

  10. Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis.

    PubMed

    Ren, Gai-Xian; Fan, Sai; Guo, Xiao-Peng; Chen, Shiyun; Sun, Yi-Cheng

    2016-01-01

    Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments. PMID:27375563

  11. Focusing the lens of language experience: perception of Ma'di stops by Greek and English bilinguals and monolinguals.

    PubMed

    Antoniou, Mark; Best, Catherine T; Tyler, Michael D

    2013-04-01

    Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek-English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals' discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group. PMID:23556605

  12. Evaluation of a di-O-methylated glycan as a potential antigenic target for the serodiagnosis of human toxocariasis.

    PubMed

    Elefant, G R; Roldán, W H; Seeböck, A; Kosma, P

    2016-04-01

    Serodiagnosis of human toxocariasis is based on the detection of specific IgG antibodies by the enzyme-linked immunosorbent assay (ELISA) using Toxocara larvae excretory-secretory (TES) antigens, but its production is a laborious and time-consuming process being also limited by the availability of adult females of T. canis as source for ova to obtain larvae. Chemical synthesis of the di-O-methylated (DiM) glycan structure found in the TES antigens has provided material for studying the antibody reactivity in a range of mammalian hosts, showing reactivity with human IgM and IgG. In this study, we have evaluated the performance of the DiM glycan against a panel of sera including patients with toxocariasis (n = 60), patients with other helminth infections (n = 75) and healthy individuals (n = 94), showing that DiM is able to detect IgG antibodies with a sensitivity and specificity of 91·7% and 94·7%, respectively, with a very good agreement with the TES antigens (kappa = 0·825). However, cross-reactivity was observed in some sera from patients with ascariasis, hymenolepiasis and fascioliasis. These results show that the DiM glycan could be a promising antigenic tool for the serodiagnosis of human toxocariasis.

  13. Di-Leucine Signals Mediate Targeting of Tyrosinase and Synaptotagmin to Synaptic-like Microvesicles within PC12 Cells

    PubMed Central

    Blagoveshchenskaya, Anastasiya D.; Hewitt, Eric W.; Cutler, Daniel F.

    1999-01-01

    One pathway in forming synaptic-like microvesicles (SLMV) involves direct budding from the plasma membrane, requires adaptor protein 2 (AP2) and is brefeldin A (BFA) resistant. A second route leads from the plasma membrane to an endosomal intermediate from which SLMV bud in a BFA-sensitive, AP3-dependent manner. Because AP3 has been shown to bind to a di-leucine targeting signal in vitro, we have investigated whether this major class of targeting signals is capable of directing protein traffic to SLMV in vivo. We have found that a di-leucine signal within the cytoplasmic tail of human tyrosinase is responsible for the majority of the targeting of HRP-tyrosinase chimeras to SLMV in PC12 cells. Furthermore, we have discovered that a Met-Leu di-hydrophobic motif within the extreme C terminus of synaptotagmin I supports 20% of the SLMV targeting of a CD4-synaptotagmin chimera. All of the traffic to the SLMV mediated by either di-Leu or Met-Leu is BFA sensitive, strongly suggesting a role for AP3 and possibly for an endosomal intermediate in this process. The differential reduction in SLMV targeting for HRP-tyrosinase and CD4-synaptotagmin chimeras by di-alanine substitutions or BFA treatment implies that different proteins use the two routes to the SLMV to differing extents. PMID:10564285

  14. Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking

    PubMed Central

    Dubey, Badri N.; Lori, Christian; Ozaki, Shogo; Fucile, Geoffrey; Plaza-Menacho, Ivan; Jenal, Urs; Schirmer, Tilman

    2016-01-01

    Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di–guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling. PMID:27652341

  15. Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking

    PubMed Central

    Dubey, Badri N.; Lori, Christian; Ozaki, Shogo; Fucile, Geoffrey; Plaza-Menacho, Ivan; Jenal, Urs; Schirmer, Tilman

    2016-01-01

    Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di–guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling.

  16. Evaluation of a di-O-methylated glycan as a potential antigenic target for the serodiagnosis of human toxocariasis.

    PubMed

    Elefant, G R; Roldán, W H; Seeböck, A; Kosma, P

    2016-04-01

    Serodiagnosis of human toxocariasis is based on the detection of specific IgG antibodies by the enzyme-linked immunosorbent assay (ELISA) using Toxocara larvae excretory-secretory (TES) antigens, but its production is a laborious and time-consuming process being also limited by the availability of adult females of T. canis as source for ova to obtain larvae. Chemical synthesis of the di-O-methylated (DiM) glycan structure found in the TES antigens has provided material for studying the antibody reactivity in a range of mammalian hosts, showing reactivity with human IgM and IgG. In this study, we have evaluated the performance of the DiM glycan against a panel of sera including patients with toxocariasis (n = 60), patients with other helminth infections (n = 75) and healthy individuals (n = 94), showing that DiM is able to detect IgG antibodies with a sensitivity and specificity of 91·7% and 94·7%, respectively, with a very good agreement with the TES antigens (kappa = 0·825). However, cross-reactivity was observed in some sera from patients with ascariasis, hymenolepiasis and fascioliasis. These results show that the DiM glycan could be a promising antigenic tool for the serodiagnosis of human toxocariasis. PMID:26896376

  17. ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa

    PubMed Central

    Kong, Weina; Zhao, Jingru; Kang, Huaping; Zhu, Miao; Zhou, Tianhong; Deng, Xin; Liang, Haihua

    2015-01-01

    AlgR is a key transcriptional regulator required for the expression of multiple virulence factors, including type IV pili and alginate in Pseudomonas aeruginosa. However, the regulon and molecular regulatory mechanism of AlgR have yet to be fully elucidated. Here, among 157 loci that were identified by a ChIP-seq assay, we characterized a gene, mucR, which encodes an enzyme that synthesizes the intracellular second messenger cyclic diguanylate (c-di-GMP). A ΔalgR strain produced lesser biofilm than did the wild-type strain, which is consistent with a phenotype controlled by c-di-GMP. AlgR positively regulates mucR via direct binding to its promoter. A ΔalgRΔmucR double mutant produced lesser biofilm than did the single ΔalgR mutant, demonstrating that c-di-GMP is a positive regulator of biofilm formation. AlgR controls the levels of c-di-GMP synthesis via direct regulation of mucR. In addition, the cognate sensor of AlgR, FimS/AlgZ, also plays an important role in P. aeruginosa virulence. Taken together, this study provides new insights into the AlgR regulon and reveals the involvement of c-di-GMP in the mechanism underlying AlgR regulation. PMID:26206672

  18. Focusing the lens of language experience: Perception of Ma'di stops by Greek and English bilinguals and monolinguals

    PubMed Central

    Antoniou, Mark; Best, Catherine T.; Tyler, Michael D.

    2013-01-01

    Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek–English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals’ discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group. PMID:23556605

  19. High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

    PubMed

    Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

    2016-05-01

    The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour.

  20. ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa.

    PubMed

    Kong, Weina; Zhao, Jingru; Kang, Huaping; Zhu, Miao; Zhou, Tianhong; Deng, Xin; Liang, Haihua

    2015-09-30

    AlgR is a key transcriptional regulator required for the expression of multiple virulence factors, including type IV pili and alginate in Pseudomonas aeruginosa. However, the regulon and molecular regulatory mechanism of AlgR have yet to be fully elucidated. Here, among 157 loci that were identified by a ChIP-seq assay, we characterized a gene, mucR, which encodes an enzyme that synthesizes the intracellular second messenger cyclic diguanylate (c-di-GMP). A ΔalgR strain produced lesser biofilm than did the wild-type strain, which is consistent with a phenotype controlled by c-di-GMP. AlgR positively regulates mucR via direct binding to its promoter. A ΔalgRΔmucR double mutant produced lesser biofilm than did the single ΔalgR mutant, demonstrating that c-di-GMP is a positive regulator of biofilm formation. AlgR controls the levels of c-di-GMP synthesis via direct regulation of mucR. In addition, the cognate sensor of AlgR, FimS/AlgZ, also plays an important role in P. aeruginosa virulence. Taken together, this study provides new insights into the AlgR regulon and reveals the involvement of c-di-GMP in the mechanism underlying AlgR regulation.

  1. Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis.

    PubMed

    Ren, Gai-Xian; Fan, Sai; Guo, Xiao-Peng; Chen, Shiyun; Sun, Yi-Cheng

    2016-01-01

    Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments.

  2. 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.

  3. Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis

    PubMed Central

    Ren, Gai-Xian; Fan, Sai; Guo, Xiao-Peng; Chen, Shiyun; Sun, Yi-Cheng

    2016-01-01

    Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments. PMID:27375563

  4. DiFX: A Software Correlator for Very Long Baseline Interferometry Using Multiprocessor Computing Environments

    NASA Astrophysics Data System (ADS)

    Deller, A. T.; Tingay, S. J.; Bailes, M.; West, C.

    2007-03-01

    We describe the development of an FX-style correlator for very long baseline interferometry (VLBI), implemented in software and intended to run in multiprocessor computing environments, such as large clusters of commodity machines (Beowulf clusters) or computers specifically designed for high-performance computing, such as multiprocessor shared-memory machines. We outline the scientific and practical benefits for VLBI correlation, these chiefly being due to the inherent flexibility of software and the fact that the highly parallel and scalable nature of the correlation task is well suited to a multiprocessor computing environment. We suggest scientific applications where such an approach to VLBI correlation is most suited and will give the best returns. We report detailed results from the Distributed FX (DiFX) software correlator running on the Swinburne supercomputer (a Beowulf cluster of ~300 commodity processors), including measures of the performance of the system. For example, to correlate all Stokes products for a 10 antenna array with an aggregate bandwidth of 64 MHz per station, and using typical time and frequency resolution, currently requires an order of 100 desktop-class compute nodes. Due to the effect of Moore's law on commodity computing performance, the total number and cost of compute nodes required to meet a given correlation task continues to decrease rapidly with time. We show detailed comparisons between DiFX and two existing hardware-based correlators: the Australian Long Baseline Array S2 correlator and the NRAO Very Long Baseline Array correlator. In both cases, excellent agreement was found between the correlators. Finally, we describe plans for the future operation of DiFX on the Swinburne supercomputer for both astrophysical and geodetic science.

  5. Effect of Inhomogeneous Mixture Properties on CI Combustion in a Schnurle-Type Gasoline DI Engine

    NASA Astrophysics Data System (ADS)

    Kim, Seok-Woo; Moriyoshi, Yasuo

    The authors have performed experiments on compression-ignition (CI) for a single-cylinder Schnurle-type two-stroke gasoline direct injection (DI) engine which employs a variable exhaust port, area, and deduced two presumptions from the experimental results. Firstly, the spatial distributions of fuel concentration and in-cylinder gas temperature are indispensable to enable CI operation under stratified charge conditions, because CI operation is not possible in a DI system although the necessary conditions of the scavenging efficiency and the in-cylinder gas temperature for the initiation of CI in homogeneous charge conditions are satisfied. Secondly, it is possible that flame propagation occurs in stratified charge CI conditions, because the combustion period in the later stage after 80% mass burned becomes longer than that with homogeneous charge CI combustion. In this report, in order to verify the above two presumptions deduced from experiments, the gas exchange process and mixture formation process were numerically analyzed, and the initiation conditions of CI were estimated using a CHEMKIN application. As a result, in case of CI with a late injection timing in DI system, it was found that CI was possible because high temperature but no fuel region and low temperature but rich fuel region exist in the cylinder due to inhomogeneous spatial distributions of fuel and temperature. Also, in case of CI with a late injection timing, the flame propagation was possible in the low-temperature and diluted rich region. Thereby, the two presumptions deduced from the experimental results were validated from the numerical analysis results.

  6. Effects of Injector Conditions on the Flame Lift-Off Length of DI Diesel Sprays

    SciTech Connect

    D. L. Siebers; B. S. Higgins

    2000-07-01

    The effects of injection pressure and orifice diameter on the lift-off length of a direct-injection (DI) diesel spray (defined as the farthest upstream location of high temperature combustion) were investigated using a natural light emission imaging technique. The lift-off length experiments were conducted in a constant-volume combustion vessel under quiescent, heavy-duty DI diesel engine conditions using a Phillips research grade No.2 diesel fuel. The results show that natural light emission at 310 nm provides an excellent marker of the lift-off length. At this location, natural light emission at 310 nm is dominated by OH chemiluminescence generated by high-temperature combustion chemistry. Lift-off lengths determined from images of natural light emission at 310 nm show that as either injection pressure (i.e., injection velocity) or orifice diameter increase, the lift-off length increases. The observed lift-off length increase was linearly dependent on injection velocity, the same dependency as previously noted for gas jets. The lift-off length increase with increasing orifice diameter, however, is different than the independence of lift-off length on orifice diameter noted for gas jets An important overall observation was made by considering the lift-off length data in conjunction with data from recent investigations of liquid-phase fuel penetration and spray development. The combined data suggests that a systematic evolution of the relationship and interaction between various processes in a DI diesel spray has been occurring over time, as injection pressures have been increased and orifice diameters reduced as part of efforts to meet emissions regulations. The trends observed may eventually help explain effects of parameters such as injection pressure and orifice diameter on emissions.

  7. Magnetocaloric properties of manganese(III) porphyrins bearing 2,6-di-tert-butylphenol groups

    NASA Astrophysics Data System (ADS)

    Korolev, V. V.; Lomova, T. N.; Maslennikova, A. N.; Korolev, D. V.; Shpakovsky, D. B.; Zhang, Jianwei; Milaeva, E. R.

    2016-03-01

    Magnetocaloric effect (MCE) and heat capacity during the magnetization of (5,10,15,20-tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)porphynato) manganese (III) chloride (1), (5-(4-hydroxyphenyl)-10,15,20-tris(3,5-di-tert-butyl-4-hydroxyphenyl)porphynato) manganese (III) chloride (2), and (5-(4-palmitoyloxyphenyl)-10,15,20-tris(3,5-di-tert-butyl-4-hydroxyphenyl)porphynato) manganese (III) chloride (3) in their aqueous suspensions were determined by the microcalorimetric method over the temperature range of 278-320 K and in magnetic fields from 0 to 1 T. MCE was positive for all complexes studied, i.e. the magnetic field impression under adiabatic conditions led to an increase in temperature of the complexes suspensions. MCE increased with an increase in the magnetic field induction at all temperatures studied. Dependences of MCE on temperature had weak maxima at 298 K at all magnetic induction values. The disturbance of the intermolecular hydrogen-bonding of hydroxyl groups is one of probable reasons for such dependences type. MCE values increased under the palmitoyl substituent incorporation into one of the phenol groups at all temperatures. The heat capacity of the studied complexes rose slightly with temperature growth. Dependences of the heat capacity on temperature showed that the magnetic component of the heat capacity did not appear due to the presence of the manganese atom acting as a paramagnetic center in complexes 1, 2, and 3. The relation between the complexes structure and their magnetothermal properties was analyzed. It was justified that the changes of magnetothermal properties were caused by electronic substitution effects and, to an even greater degree, by the conditions of intermolecular hydrogen bonds formation in the paramagnetic materials.

  8. High abundance of novel environmental chlamydiae in a Tyrrhenian coastal lake (Lago di Paola, Italy).

    PubMed

    Pizzetti, Ilaria; Fazi, Stefano; Fuchs, Bernhard M; Amann, Rudolf

    2012-08-01

    For a long time the bacterial phylum of Chlamydiae exclusively consisted of one family of obligate intracellular bacteria, the Chlamydiaceae, which encompassed causative agents of severe diseases. In the 1990s, environmental chlamydiae were discovered as symbionts of free-living amoebae and other eukaryotic hosts. During a sampling campaign in September 2008, while monitoring Planctomycetes, we retrieved 20 almost full-length 16S rRNA gene sequences affiliated with Chlamydiales from a lake at the Tyrrhenian coast of central Italy (Lago di Paola, Latium). Two main clusters were identified. The nine sequences within the tight cluster I shared ∼98% identity, just like the six sequences of cluster II. The 16S rRNA sequence identity between the two novel groups was with 88% higher than with all known families of the order Chlamydiales. Four types of less frequent chlamydial 16S rRNA sequences were also detected. Two oligonucleotide probes were designed, and optimized. Chl282 targets the cluster I and almost all other Chlamydiales, while Chl282bis targets the cluster II and few other sequences. By catalysed reporter deposition fluorescence in situ hybridization (CARD-FISH), we identified in the Lago di Paola picoplankton abundant tiny cells with dot-shaped morphology and, interestingly, rarely also protists with intracellular pleomorphic chlamydiae. Abundances of the novel chlamydial clusters were up to 5 × 10(4) cells per millilitre. The two clusters were also detected in similar numbers during a second sampling in October 2010. This confirmed the relevance of the two newly described clusters of chlamydiae in Lago di Paola, not only enlarging the knowledge on the biodiversity of environmental chlamydiae in aquatic habitats, but also raising sanitary issues that should be addressed in the future.

  9. Spin-Orbit Coupling Effects in Di-Hydrides of Third-Row Transition Elements

    NASA Astrophysics Data System (ADS)

    Koseki, Shiro

    2007-11-01

    Spin-orbit coupling (SOC) effects were investigated for low-lying electronic states in the di-hydrides of third-row transition elements by using MCSCF+MRMP2, +FOCI, and +SOCI methods with the SBKJC basis sets augmented by a set of f functions for transition elements and a set of p functions for hydrogen atoms, where MCSCF, MRMP2, FOCI, and SOCI are abbreviations of multi-configuration self-consistent field, multi-reference second-order Mo/ller-Plesset, first-order configuration interaction, and second-order configuration interaction, respectively. Before the inclusion of SOC effects, six di-hydrides (LaH2, HfH2, TaH2, WH2, OsH2, and IrH2) are lower in energy than the corresponding dissociation limits (transition element and a hydrogen molecule). All of these di-hydrides have bent structures at their energy minima, and the ground states are 2A1, 1A1, 4B1, 5B2, 3B2, and 2A1, respectively. After the inclusion of SOC effects, the ground states are assigned to E1/2, A1, E1/2, A1, A1, and E1/2 in the double-group representation of C2v symmetry. It can be concluded that SOC effects are not so important in LaH2, HfH2, and TaH2, while they become important in describing bending potential energy curves of low-lying electronic states in WH2, OsH2, and IrH2.

  10. Di-J/Ψ Studies, Level 3 Tracking and the D0 Run IIb Upgrade

    SciTech Connect

    Vint, Philip John

    2010-02-01

    The D0 detector underwent an upgrade to its silicon vertex detector and triggering systems during the transition from Run IIa to Run IIb to maximize its ability to fully exploit Run II at the Fermilab Tevatron. This thesis describes improvements made to the tracking and vertexing algorithms used by the high level trigger in both Run IIa and Run IIb, as well as a search for resonant di-J/Ψ states using both Run IIa and Run IIb data. Improvements made to the tracking and vertexing algorithms during Run IIa included the optimization of the existing tracking software to reduce overall processing time and the certification and testing of a new software release. Upgrades made to the high level trigger for Run IIb included the development of a new tracking algorithm and the inclusion of the new Layer 0 silicon detector into the existing software. The integration of Layer 0 into the high level trigger has led to an improvement in the overall impact parameter resolution for tracks of ~50%. The development of a new parameterization method for finding the error associated to the impact parameter of tracks returned by the high level tracking algorithm, in association with the inclusion of Layer 0, has led to improvements in vertex resolution of ~4.5 μm. A previous search in the di-J/Ψ channel revealed a unpredicted resonance at ~13.7 GeV/c2. A confirmation analysis is presented using 2.8 fb-1 of data and two different approaches to cuts. No significant excess is seen in the di-J/Ψ mass spectrum.

  11. [Medico-psychology in Huang di nei jing (Yellow Emperor's Inner Canon)].

    PubMed

    Yang, Li-Min

    2004-01-01

    Huang di nei jing (Yellow Emperor's Inner Canon) discusses spirit, mood, soul, idea, will, anxiety, worry, wisdom, morale and their relations with human life, physiology, and body-mind health. It also expounds the developmental rule of human body and mind, methods for keeping fit. These simple thinking of medico-psychology reflects that Chinese doctors had advocated science since ancient times. The methodology of systematically and comprehensively discussing the relationship among nature, human body, visceral functions, and emotional activities reflects, again, the rather strong physiological dialectical thinking of ancient people. PMID:15555247

  12. The meteorite collection at Museo di Storia Naturale, Pisa University, Italy

    NASA Astrophysics Data System (ADS)

    Perchiazzi, Natale; D'Orazio, Massimo; Folco, Luigi

    2004-08-01

    The historical meteorite collection of Museo di Storia Naturale, Pisa University, is presented in this catalog. Dating back to at least 1860, the collection currently (as of June 2003) contains 30 specimens of 26 individual meteorites, representing about 50 kg of extraterrestrial material. The collection includes 2 carbonaceous chondrites, 12 ordinary chondrites, 1 achondrite, 4 stony-iron meteorites, and 7 iron meteorites, including three remarkable specimens: the main mass of Bagnone (48 kg), the fourth largest mass of Quenggouk (717.5 g), and a large (nearly) complete individual of the Siena showerfall (318.8 g).

  13. Propane-1,2-di­ammonium chromate(VI)

    PubMed Central

    Trabelsi, Sonia; Essid, Manel; Roisnel, Thierry; Rzaigui, Mohamed; Marouani, Houda

    2014-01-01

    In the title mol­ecular salt, (C3H12N2)[CrO4], each chromate anion accepts six N—H⋯O and C—H⋯O hydrogen bonds from nearby propane-1,2-di­ammonium cations. Three of the four O atoms of the chromate anion accept these bonds; the remaining Cr—O bond length is notably shorter than the others. In the crystal, the anions and cations stack in layers lying parallel to (100): the hydrogen-bonding pattern leads to a three-dimensional network. PMID:24764949

  14. Big Data Sensors of Organic Advocacy: The Case of Leonardo DiCaprio and Climate Change

    PubMed Central

    Althouse, Benjamin M.; Dredze, Mark; Obradovich, Nick; Fowler, James H.; Noar, Seth M.; Allem, Jon-Patrick

    2016-01-01

    The strategies that experts have used to share information about social causes have historically been top-down, meaning the most influential messages are believed to come from planned events and campaigns. However, more people are independently engaging with social causes today than ever before, in part because online platforms allow them to instantaneously seek, create, and share information. In some cases this “organic advocacy” may rival or even eclipse top-down strategies. Big data analytics make it possible to rapidly detect public engagement with social causes by analyzing the same platforms from which organic advocacy spreads. To demonstrate this claim we evaluated how Leonardo DiCaprio’s 2016 Oscar acceptance speech citing climate change motivated global English language news (Bloomberg Terminal news archives), social media (Twitter postings) and information seeking (Google searches) about climate change. Despite an insignificant increase in traditional news coverage (54%; 95%CI: -144 to 247), tweets including the terms “climate change” or “global warming” reached record highs, increasing 636% (95%CI: 573–699) with more than 250,000 tweets the day DiCaprio spoke. In practical terms the “DiCaprio effect” surpassed the daily average effect of the 2015 Conference of the Parties (COP) and the Earth Day effect by a factor of 3.2 and 5.3, respectively. At the same time, Google searches for “climate change” or “global warming” increased 261% (95%CI, 186–335) and 210% (95%CI 149–272) the day DiCaprio spoke and remained higher for 4 more days, representing 104,190 and 216,490 searches. This increase was 3.8 and 4.3 times larger than the increases observed during COP’s daily average or on Earth Day. Searches were closely linked to content from Dicaprio’s speech (e.g., “hottest year”), as unmentioned content did not have search increases (e.g., “electric car”). Because these data are freely available in real time our

  15. Big Data Sensors of Organic Advocacy: The Case of Leonardo DiCaprio and Climate Change.

    PubMed

    Leas, Eric C; Althouse, Benjamin M; Dredze, Mark; Obradovich, Nick; Fowler, James H; Noar, Seth M; Allem, Jon-Patrick; Ayers, John W

    2016-01-01

    The strategies that experts have used to share information about social causes have historically been top-down, meaning the most influential messages are believed to come from planned events and campaigns. However, more people are independently engaging with social causes today than ever before, in part because online platforms allow them to instantaneously seek, create, and share information. In some cases this "organic advocacy" may rival or even eclipse top-down strategies. Big data analytics make it possible to rapidly detect public engagement with social causes by analyzing the same platforms from which organic advocacy spreads. To demonstrate this claim we evaluated how Leonardo DiCaprio's 2016 Oscar acceptance speech citing climate change motivated global English language news (Bloomberg Terminal news archives), social media (Twitter postings) and information seeking (Google searches) about climate change. Despite an insignificant increase in traditional news coverage (54%; 95%CI: -144 to 247), tweets including the terms "climate change" or "global warming" reached record highs, increasing 636% (95%CI: 573-699) with more than 250,000 tweets the day DiCaprio spoke. In practical terms the "DiCaprio effect" surpassed the daily average effect of the 2015 Conference of the Parties (COP) and the Earth Day effect by a factor of 3.2 and 5.3, respectively. At the same time, Google searches for "climate change" or "global warming" increased 261% (95%CI, 186-335) and 210% (95%CI 149-272) the day DiCaprio spoke and remained higher for 4 more days, representing 104,190 and 216,490 searches. This increase was 3.8 and 4.3 times larger than the increases observed during COP's daily average or on Earth Day. Searches were closely linked to content from Dicaprio's speech (e.g., "hottest year"), as unmentioned content did not have search increases (e.g., "electric car"). Because these data are freely available in real time our analytical strategy provides substantial lead time

  16. Big Data Sensors of Organic Advocacy: The Case of Leonardo DiCaprio and Climate Change.

    PubMed

    Leas, Eric C; Althouse, Benjamin M; Dredze, Mark; Obradovich, Nick; Fowler, James H; Noar, Seth M; Allem, Jon-Patrick; Ayers, John W

    2016-01-01

    The strategies that experts have used to share information about social causes have historically been top-down, meaning the most influential messages are believed to come from planned events and campaigns. However, more people are independently engaging with social causes today than ever before, in part because online platforms allow them to instantaneously seek, create, and share information. In some cases this "organic advocacy" may rival or even eclipse top-down strategies. Big data analytics make it possible to rapidly detect public engagement with social causes by analyzing the same platforms from which organic advocacy spreads. To demonstrate this claim we evaluated how Leonardo DiCaprio's 2016 Oscar acceptance speech citing climate change motivated global English language news (Bloomberg Terminal news archives), social media (Twitter postings) and information seeking (Google searches) about climate change. Despite an insignificant increase in traditional news coverage (54%; 95%CI: -144 to 247), tweets including the terms "climate change" or "global warming" reached record highs, increasing 636% (95%CI: 573-699) with more than 250,000 tweets the day DiCaprio spoke. In practical terms the "DiCaprio effect" surpassed the daily average effect of the 2015 Conference of the Parties (COP) and the Earth Day effect by a factor of 3.2 and 5.3, respectively. At the same time, Google searches for "climate change" or "global warming" increased 261% (95%CI, 186-335) and 210% (95%CI 149-272) the day DiCaprio spoke and remained higher for 4 more days, representing 104,190 and 216,490 searches. This increase was 3.8 and 4.3 times larger than the increases observed during COP's daily average or on Earth Day. Searches were closely linked to content from Dicaprio's speech (e.g., "hottest year"), as unmentioned content did not have search increases (e.g., "electric car"). Because these data are freely available in real time our analytical strategy provides substantial lead time

  17. Crystal structure of (ferrocenylmeth-yl)di-methyl-ammonium hydrogen oxalate.

    PubMed

    Ndiaye, Mamadou; Samb, Abdoulaye; Diop, Libasse; Maris, Thierry

    2015-08-01

    The crystal structure of the title salt, [Fe(C5H5)(C8H13N)](HC2O4), consists of discrete (ferrocenylmeth-yl)di-methyl-ammonium cations and hydrogen oxalate anions. The anions are connected through a strong O-H⋯O hydrogen bond, forming linear chains running parallel to [100]. The cations are linked to the anions through bifurcated N-H⋯(O,O') hydrogen bonds. Weak C-H⋯π inter-actions between neighbouring ferrocenyl moieties are also observed. PMID:26396763

  18. Crystal structure of (ferrocenylmeth­yl)di­methyl­ammonium hydrogen oxalate

    PubMed Central

    Ndiaye, Mamadou; Samb, Abdoulaye; Diop, Libasse; Maris, Thierry

    2015-01-01

    The crystal structure of the title salt, [Fe(C5H5)(C8H13N)](HC2O4), consists of discrete (ferrocenylmeth­yl)di­methyl­ammonium cations and hydrogen oxalate anions. The anions are connected through a strong O—H⋯O hydrogen bond, forming linear chains running parallel to [100]. The cations are linked to the anions through bifurcated N—H⋯(O,O′) hydrogen bonds. Weak C—H⋯π inter­actions between neighbouring ferrocenyl moieties are also observed. PMID:26396763

  19. Unprecedented Phthalocyanines Bearing Eight Di-butylamino Peripheral Substituents: Synthesis, Spectroscopy, and Structure.

    PubMed

    Chen, Yuxiang; Cao, Wei; Wang, Kang; Jiang, Jianzhuang

    2015-10-19

    Unprecedented 2,3,9,10,16,17,23,24-octakis(di-butylamino)phthalocyanine compounds M{Pc[N(C4H9)2]8} (M = 2H, Mg, Cu, Zn) (1-4) were prepared and structurally characterized on the basis of single-crystal X-ray diffraction analysis, representing the first structurally characterized alkylamino-substituted phthalocyanine examples. These novel phthalocyanine derivatives have also been characterized by a wide range of spectroscopic methods including MALDI-TOF mass spectra, NMR, electronic absorption, and IR spectroscopy in addition to elemental analysis. Their electrochemistry was also studied by cyclic voltammetry.

  20. Uptake of di-(2-ethylhexyl) phthalate of vegetables from plastic film greenhouses.

    PubMed

    Fu, Xiaowei; Du, Qizhen

    2011-11-01

    Uptake of di-(2-ethylhexyl) phthalate (DEHP) of nine vegetables including potherb mustard, bok choy, celery, spinach, cabbage, leaf of tube, lettuce, garlic, and edible amaranth in plastic film greenhouses with different plastic films, film thickness, greenhouse age, and greenhouse height was studied. The results showed that the higher the DEHP content of film, the thicker the film, the lower the height of the greenhouse, and the younger the age of the greenhouse were, the higher the DEHP concentration of vegetables was. The results afford significant information for production of safe vegetables with low level DEHP contamination.

  1. 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

  2. Method for separating mono- and di-octylphenyl phosphoric acid esters

    DOEpatents

    Arnold, Jr., Wesley D.

    1977-01-01

    A method for separating mono-octylphenyl phosphoric acid ester and di-octylphenyl phosphoric acid ester from a mixture thereof comprises reacting the ester mixture with a source of lithium or sodium ions to form a mixture of the phosphate salts; contacting the salt mixture with an organic solvent which causes the dioctylphenyl phosphate salt to be dissolved in the organic solvent phase and the mono-octylphenyl phosphate salt to exist in a solid phase; separating the phases; recovering the phosphate salts from their respective phases; and acidifying the recovered salts to form the original phosphoric acid esters.

  3. Improvement of pattern collapse issue by additive-added D.I. water rinse process

    NASA Astrophysics Data System (ADS)

    Tanaka, Keiichi; Naito, Ryoichiro; Kitada, Tomohiro; Kiba, Yukio; Yamada, Yoshiaki; Kobayashi, Masakazu; Ichikawa, Hiroyuki

    2003-06-01

    Reduction of critical dimension in lithography technology is aggressively promoted. At the same time, further resist thickness reduction is being pursued to increase the resolution capabilities of resist. However, thin film has its limitation because of etch requirements etc. As that result, the promotion of reduction results in increasing the aspect ratio, which leads to pattern collapse. It is well known that at drying step in developing process the capillary effect operates the photoresist pattern. If the force of the capillary effect is greater than the aggregation force of the resist pattern, the pattern collapse is generated. And the key parameters of the capillary effect are the space width between patterns, the aspect ratio, the contact angle of the D.I water rinse and the surface tension of rinse solution. Among these parameters the surface tension of rinse solution can be controlled by us. On the other hand, we've already reported that the penetration of TMAH and D.I water into the resist plays an important role on the lithographic latitude. For example, when we use the resist which TMA ion can be easily diffuse into, D.I water and TMA ion which are penetrated in the resist decreases the aggregation force of resist pattern and causes the pattern collapse even by the weak force against resist pattern. These results indicate that the swelling of photoresist by TMA ion and water is very important factor for controlling the pattern collapse. Currently, two methods are mainly tried to reduce the surface tension of rinse solution: SCF (Super Critical Fluid) and addition of additive to D.I water rinse. We used the latter method this time, because this technique has retrofittability and not special tool. And in this evaluation, we found that the degree of suppressing pattern collapse depends on the additive chemistry or formulation. With consideration given to process factors such as above, we investigated what factors contribute to suppressing pattern collapse

  4. Uptake of di-(2-ethylhexyl) phthalate of vegetables from plastic film greenhouses.

    PubMed

    Fu, Xiaowei; Du, Qizhen

    2011-11-01

    Uptake of di-(2-ethylhexyl) phthalate (DEHP) of nine vegetables including potherb mustard, bok choy, celery, spinach, cabbage, leaf of tube, lettuce, garlic, and edible amaranth in plastic film greenhouses with different plastic films, film thickness, greenhouse age, and greenhouse height was studied. The results showed that the higher the DEHP content of film, the thicker the film, the lower the height of the greenhouse, and the younger the age of the greenhouse were, the higher the DEHP concentration of vegetables was. The results afford significant information for production of safe vegetables with low level DEHP contamination. PMID:21958198

  5. Xenon Difluoride Mediated Fluorodecarboxylations for the Syntheses of Di- and Trifluoromethoxyarenes.

    PubMed

    Chatalova-Sazepin, Claire; Binayeva, Meruyert; Epifanov, Maxim; Zhang, Wei; Foth, Paul; Amador, Carolyn; Jagdeo, Manu; Boswell, Benjamin R; Sammis, Glenn M

    2016-09-16

    XeF2 is demonstrated to be a more proficient fluorine-transfer reagent than either NFSI or Selectfluor in fluorodecarboxylations of both mono- and difluoroaryloxy acetic acid derivatives. This method efficiently converts a wide range of neutral and electron-poor substrates to afford the desired di- and trifluoromethyl aryl ethers in good to excellent yields. The purifications are facile, and the reaction times are less than 5 min, which makes these fluorodecarboxylations promising for future PET-imaging applications. PMID:27560791

  6. Structural and spectroscopic investigation on a new potentially bioactive di-hydrazone containing thiophene heterocyclic rings

    NASA Astrophysics Data System (ADS)

    Nogueira, Vanessa de S.; Ramalho Freitas, Maria Clara; Cruz, Wellington S.; Ribeiro, Tatiana S.; Resende, Jackson A. L. C.; Rey, Nicolás A.

    2016-02-01

    Hydrazones and several substituted hydrazones are associated with a broad spectrum of biological activities, as well as compounds containing the thiophene ring. In this context, a novel di-hydrazone derived from 2-thiophenecarboxylic acid hydrazide was synthesized and completely characterized by elemental analysis, XRD, FT-IR, Raman and UV-Vis spectroscopies, thermogravimetry, 1H NMR, 1H-1H COSY and 1H-1H ROESY. A preliminary in silico pharmacological evaluation was also performed in order to assess the performance of the new compound regarding some molecular properties relevant for a drug's pharmacokinetics in the human body.

  7. Improved di-p-xylylene polymer and apparatus and method for making the same

    DOEpatents

    Jahn, R.K.; Liepins, R.

    Solid di-para-xylyene dimer is sublimed in a sublimation furnace at approximately 100 to 200/sup 0/C and subsequently conducted to a pyrolysis furnace where it is pyrolyzed to the diradical p-xylylene monomer while in the vapor state at approximately 600 degrees C. The diradical monomer is then introduced into a deposition chamber for deposition onto a suitable substrate. The deposition chamber includes electrodes for producing a low pressure plasma through which the diradical monomer passes prior to deposition. The interaction of the diradical monomer with the low pressure plasma results in the formation of poly-p-xylyene film which is exceptionally hard and thermally stable.

  8. [Biodegradation of di-n-butyl phthalate by mangrove microorganism Rhodococcus ruber 1K].

    PubMed

    Li, Kuixiao; Gu, Jidong

    2005-08-01

    A di-n-butyl phthalate (DBP)degrading bacterium Rhodococcus ruber was isolated from mangrove soil, and its degrading characteristics were studied. The results showed that the bacterium could grow well on the substrate with DBP as the sole source of carbon and energy, and the DBP of 50 mg x L(-1) could be completely degraded after 48 h. Under aerobic condition, the tentative pathway proposed for DBP degradation was through monoester initially, then phthalic acid, and finally CO2 and H2O.

  9. Crystal structure of (μ-1,4-di-carb-oxy-butane-1,4-di-carboxyl-ato)bis-[bis-(tri-phenyl-phosphane)silver(I)] di-chloro-methane tris-olvate.

    PubMed

    Frenzel, Peter; Korb, Marcus; Lang, Heinrich

    2016-02-01

    The mol-ecular structure of the tetra-kis(tri-phenyl-phosphan-yl)disilver salt of butane-1,1,4,4-tetra-carb-oxy-lic acid, [Ag2(C8H8O8)(C18H15P)4]·3CH2Cl2, crystallizes with one and a half mol-ecules of di-chloro-methane in the asymmetric unit. The coordination complex exhibits an inversion centre through the central CH2-CH2 bond. The Ag(I) atom has a distorted trigonal-planar P2O coordination environment. The packing is characterized by inter-molecular T-shaped π-π inter-actions between the phenyl rings of the PPh3 substituents in neighbouring mol-ecules, forming a ladder-type superstructure parallel to [010]. These ladders are arranged in layers parallel to (101). Intra-molecular hydrogen bonds between the OH group and one O atom of the Ag-bonded carboxyl-ate group results in an asymmetric bidendate coordination of the carboxyl-ate moiety to the Ag(I) ion. PMID:26958391

  10. Structural characterization of two benzene-1,2-di-amine complexes of zinc chloride: a mol-ecular compound and a co-crystal salt.

    PubMed

    Zick, Patricia L; Geiger, David K

    2016-07-01

    The structures of two zinc complexes containing bidentate benzene-1,2-di-amine ligands are reported. (Benzene-1,2-di-amine-κ(2) N,N')di-chloro-idozinc, [ZnCl2(C6H8N2)], (I), displays a distorted tetra-hedral coordination sphere for the metal cation. The di-amine ligand and the Zn atom reside on a crystallographic mirror plane. In the 1:1 co-crystal salt trans-di-aqua-bis-(4,5-di-methyl-benzene-1,2-di-amine-κ(2) N,N')zinc chloride-4,5-di-methyl-benzene-1,2-di-amine (1/1), [Zn(C8H12N2)2(H2O)2]Cl2·2C8H12N2, (II), the zinc(II) complex cation exhibits a tetra-gonally distorted octa-hedral coordination sphere. The Zn atom sits on a crystallographically imposed inversion center and the di-amine ligands are tilted 30.63 (6)° with respect to the ZnN4 plane. Both complexes exhibit extensive hydrogen bonding. In (I), a stacked-sheet extended structure parallel to (101) is observed. In (II), the co-crystallized di-amine is hydrogen-bonded to the complex cation via O-H⋯N and N-H⋯N linkages. These units are in turn linked into planes along (200) by O-H⋯Cl and N-H⋯Cl hydrogen bonds. PMID:27555958

  11. Structural characterization of two benzene-1,2-di­amine complexes of zinc chloride: a mol­ecular compound and a co-crystal salt

    PubMed Central

    Zick, Patricia L.; Geiger, David K.

    2016-01-01

    The structures of two zinc complexes containing bidentate benzene-1,2-di­amine ligands are reported. (Benzene-1,2-di­amine-κ2 N,N′)di­chloro­idozinc, [ZnCl2(C6H8N2)], (I), displays a distorted tetra­hedral coordination sphere for the metal cation. The di­amine ligand and the Zn atom reside on a crystallographic mirror plane. In the 1:1 co-crystal salt trans-di­aqua­bis­(4,5-di­methyl­benzene-1,2-di­amine-κ2 N,N′)zinc chloride–4,5-di­methyl­benzene-1,2-di­amine (1/1), [Zn(C8H12N2)2(H2O)2]Cl2·2C8H12N2, (II), the zinc(II) complex cation exhibits a tetra­gonally distorted octa­hedral coordination sphere. The Zn atom sits on a crystallographically imposed inversion center and the di­amine ligands are tilted 30.63 (6)° with respect to the ZnN4 plane. Both complexes exhibit extensive hydrogen bonding. In (I), a stacked-sheet extended structure parallel to (101) is observed. In (II), the co-crystallized di­amine is hydrogen-bonded to the complex cation via O—H⋯N and N—H⋯N linkages. These units are in turn linked into planes along (200) by O—H⋯Cl and N—H⋯Cl hydrogen bonds. PMID:27555958

  12. On the Use of 3,5-Di-O-benzylidene and 3,5-Di-O-(di-tert-butylsilylene)-2-O-benzylarabinothiofuranosides and their Sulfoxides as Glycosyl Donors for the Synthesis of β-Arabinofuranosides: Importance of the Activation Method

    PubMed Central

    Crich, David; Pedersen, Christian Marcus; Bowers, Albert A.; Wink, Donald J.

    2008-01-01

    A 2-O-benzyl-3,5-di-O-benzylidene-α-d-thioarabinofuranoside was obtained by reaction of the corresponding diol with α,α-dibromotoluene under basic conditions. On activation with 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride in dichloromethane at −56 °C, reaction with glycosyl acceptors affords anomeric mixtures with little or no selectivity. The analogous 2-O-benzyl-3,5-di-O-(di-tert-butylsilylene)-α-d-thioarabinofuranoside also showed no significant selectivity under the 1-benzenesulfinyl piperidine or diphenyl sulfoxide conditions. With N-iodosuccinimide and silver trifluoromethanesulfonate the silylene acetal showed moderate to high β-selectivity, independent of the configuration of the starting thioglycoside. High β-selectivity was also obtained with a 2-O-benzyl-3,5-di-O-(di-tert-butylsilylene)-α-arabinofuranosyl sulfoxide donor on activation with trifluoromethanesulfonic anhydride. The high β-selectivities obtained by the N-iodosuccinimide/silver trifluoromethanesulfonate and sulfoxide methods are consistent with a common intermediate, most likely to be the oxacarbenium ion. The poor selectivity observed on activation of the thioglycosides with the 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride methods appears to be the result of the formation of a complex mixture of glycosyl donors, as determined by low temperature NMR work. PMID:17286432

  13. Synthesis of new 2,5-di-substituted 1,3,4-oxadiazoles bearing 2,6-di-tert-butylphenol moieties and evaluation of their antioxidant activity.

    PubMed

    Shakir, Raied M; Ariffin, Azhar; Abdulla, Mahmood Ameen

    2014-01-01

    Eleven new 2,6-di-tert-butyl-4-(5-aryl-1,3,4-oxadiazol-2-yl)phenols 5a-k were synthesized by reacting aryl hydrazides with 3,5-di-tert butyl 4-hydroxybenzoic acid in the presence of phosphorus oxychloride. The resulting compounds were characterized based on their IR, ¹H-NMR, ¹³C-NMR, and HRMS data. 2,2-Diphenyl-1-picrylhydrazide (DPPH) and ferric reducing antioxidant power (FRAP) assays were used to test the antioxidant properties of the compounds. Compounds 5f and 5j exhibited significant free-radical scavenging ability in both assays.

  14. Degradation pathway of 2,5-di-tert-butyl-1,4-dimethoxybenzene at high potential.

    SciTech Connect

    Chen, Z.; Amine, K.; Chemical Engineering

    2007-01-01

    2,5-Di-tert-butyl-1,4-dimethoxybenzene is a redox shuttle for overcharge protection of LiFePO{sub 4}-based lithium-ion batteries with a working potential lower than 4.2 V versus Li{sup +}/Li. However, an irreversible decomposition occurs when the working potential is higher than 4.2 V versus Li{sup +}/Li. 2,3,5,6-Tetrafluoro-1,4-di-tert-butoxybenzene was also investigated as a model molecule to further understand the possible degradation pathway of 2,5-di-tert-butyl-1,4-dimethxybenzene. The experimental results strongly suggest that the irreversible reaction be related to the decomposition of OC bond in alkoxy substitution groups.

  15. Design of PACs for high-performance photoresists (I): role of di-esterified PACs having hindered -OH groups

    NASA Astrophysics Data System (ADS)

    Hanawa, Ryotaro; Uetani, Yasunori; Hanabata, Makoto

    1992-06-01

    Steric hindrance on a ballast molecule causes selective esterification of -OH groups and provides novel di-esterified PACs having -OH group(s) with high selectivity. These novel PACs give photoresists higher sensitivities, (gamma) -values and resolutions, than those of fully esterified PACs. Also, these novel PACs provide scum-free patterns. Comparison of dissolution properties of a novel di-esterified PAC having a sterically hindered -OH with those of a di-esterified PAC suggests that the presence of -OH enhances dissolution rates, but it does not change the slope of logR-logE plots. DRM's agitated development reduces a large (gamma) -value of a novel PAC observed in puddle development. On the other hand, (gamma) -values of fully esterified PACs were not affected by the change of development methods. This observation suggests significance of (gamma) - value evaluation by puddle development for the investigation of high performance PACs.

  16. Effects of natural compounds on microbial safety and sensory quality of Fior di Latte cheese, a typical Italian cheese.

    PubMed

    Gammariello, D; Di Giulio, S; Conte, A; Del Nobile, M A

    2008-11-01

    This work presents a preliminary study to assess the efficiency of plant essential oils as natural food preservatives in Fior di Latte cheese. Selected compounds were directly dissolved into Fior di Latte brine. Packaged Fior di Latte samples were stored at 10 degrees C for about 6 d. The cell loads of spoilage and useful microorganisms were monitored to calculate the microbial acceptability limit. Results show that some tested compounds were not acceptable by the panel from a sensorial point of view. Most compounds did not affect the microbial acceptability limit value to a great extent, and only a few such as lemon, sage, and thyme markedly prolonged the microbial acceptability limit of the investigated fresh cheese. Moreover, the above active agents exerted an inhibitory effect on the microorganisms responsible for spoilage without affecting the dairy microflora.

  17. Halimeda dominance in the coastal wedge of Pietra di Finale (Ligurian Alps, Italy): The role of trophic conditions

    NASA Astrophysics Data System (ADS)

    Brandano, Marco; Tomassetti, Laura; Frezza, Virgilio

    2015-05-01

    The Middle to Late Miocene mixed carbonate-siliciclastic coastal wedge of the Pietra di Finale, unconformably overlying the Ligurian Alps succession, displays a carbonate portion dominated by Halimeda and Porites fragments that fall in the photozoan assemblages. Photozoan assemblages typically develop under tropical and oligotrophic conditions, while hetorozoan assemblages tend to thrive in high-nutrient settings. The Pietra di Finale Formation shows, however, that high weathering and an increase of nutrient inputs related to Alpine uplift and humid climatic conditions promoted Halimeda over the seagrass carbonate factory in the photic zone. The successful Halimeda proliferation was due to its efficient competition for nutrients, especially nitrogen. Thus, the Pietra di Finale Formation represents an interesting, counter-intuitive example in which increased nutrient concentrations promoted, instead of inhibited, a photozoan over a seagrass-related heterozoan carbonate production.

  18. Mutational analysis of structural elements in a class-I cyclic di-GMP riboswitch to elucidate its regulatory mechanism.

    PubMed

    Inuzuka, Saki; Nishimura, Kei-Ichiro; Kakizawa, Hitoshi; Fujita, Yuki; Furuta, Hiroyuki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2016-09-01

    The Vc2 riboswitch possesses an aptamer domain belonging to the class-I c-di-GMP riboswitch family. This domain has been analysed and the molecular mechanism by which it recognizes the c-di-GMP ligand has been elucidated. On the other hand, the regulatory mechanism of the full-length Vc2 riboswitch to control its downstream open reading frame (ORF) remains largely unknown. In this study, we performed in vivo reporter assays and in vitro biochemical analyses of the full-length riboswitch and its aptamer domain. We evaluated the results of in vivo and in vitro analyses to elucidate the regulatory mechanism of the Vc2 riboswitch. The present results suggest that recognition of c-di-GMP ligand by the Vc2 riboswitch aptamer domain downregulates expression of its downstream ORF primarily at the translational level.

  19. The synthetic cationic lipid diC14 activates a sector of the Arabidopsis defence network requiring endogenous signalling components.

    PubMed

    Cambiagno, Damián Alejandro; Lonez, Caroline; Ruysschaert, Jean-Marie; Alvarez, María Elena

    2015-12-01

    Natural and synthetic elicitors have contributed significantly to the study of plant immunity. Pathogen-derived proteins and carbohydrates that bind to immune receptors, allow the fine dissection of certain defence pathways. Lipids of a different nature that act as defence elicitors, have also been studied, but their specific effects have been less well characterized, and their receptors have not been identified. In animal cells, nanoliposomes of the synthetic cationic lipid 3-tetradecylamino-tert-butyl-N-tetradecylpropionamidine (diC14) activate the TLR4-dependent immune cascade. Here, we have investigated whether this lipid induces Arabidopsis defence responses. At the local level, diC14 activated early and late defence gene markers (FRK1, WRKY29, ICS1 and PR1), acting in a dose-dependent manner. This lipid induced the salicylic acid (SA)-dependent, but not jasmonic acid (JA)-dependent, pathway and protected plants against Pseudomonas syringae pv. tomato (Pst), but not Botrytis cinerea. diC14 was not toxic to plant or pathogen, and potentiated pathogen-induced callose deposition. At the systemic level, diC14 induced PR1 expression and conferred resistance against Pst. diC14-induced defence responses required the signalling protein EDS1, but not NDR1. Curiously, the lipid-induced defence gene expression was lower in the fls2/efr/cerk1 triple mutant, but still unchanged in the single mutants. The amidine headgroup and chain length were important for its activity. Given the robustness of the responses triggered by diC14, its specific action on a defence pathway and the requirement for well-known defence components, this synthetic lipid is emerging as a useful tool to investigate the initial events involved in plant innate immunity.

  20. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

    SciTech Connect

    Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang; Choi, Eun-young; Son, Hwa-Young; Lee, Kyoung-Youl

    2014-02-01

    Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

  1. Mutation in the C-Di-AMP Cyclase dacA Affects Fitness and Resistance of Methicillin Resistant Staphylococcus aureus

    PubMed Central

    Dengler, Vanina; McCallum, Nadine; Kiefer, Patrick; Christen, Philipp; Patrignani, Andrea; Vorholt, Julia A.; Berger-Bächi, Brigitte; Senn, Maria M.

    2013-01-01

    Faster growing and more virulent strains of methicillin resistant Staphylococcus aureus (MRSA) are increasingly displacing highly resistant MRSA. Elevated fitness in these MRSA is often accompanied by decreased and heterogeneous levels of methicillin resistance; however, the mechanisms for this phenomenon are not yet fully understood. Whole genome sequencing was used to investigate the genetic basis of this apparent correlation, in an isogenic MRSA strain pair that differed in methicillin resistance levels and fitness, with respect to growth rate. Sequencing revealed only one single nucleotide polymorphism (SNP) in the diadenylate cyclase gene dacA in the faster growing but less resistant strain. Diadenylate cyclases were recently discovered to synthesize the new second messenger cyclic diadenosine monophosphate (c-di-AMP). Introduction of this mutation into the highly resistant but slower growing strain reduced resistance and increased its growth rate, suggesting a direct connection between the dacA mutation and the phenotypic differences of these strains. Quantification of cellular c-di-AMP revealed that the dacA mutation decreased c-di-AMP levels resulting in reduced autolysis, increased salt tolerance and a reduction in the basal expression of the cell wall stress stimulon. These results indicate that c-di-AMP affects cell envelope-related signalling in S. aureus. The influence of c-di-AMP on growth rate and methicillin resistance in MRSA indicate that altering c-di-AMP levels could be a mechanism by which MRSA strains can increase their fitness levels by reducing their methicillin resistance levels. PMID:24013956

  2. Organometallic halide perovskite/barium di-silicide thin-film double-junction solar cells

    NASA Astrophysics Data System (ADS)

    Vismara, R.; Isabella, O.; Zeman, M.

    2016-04-01

    Barium di-silicide (BaSi2) is an abundant and inexpensive semiconductor with appealing opto-electrical properties. In this work we show that a 2-μm thick BaSi2-based thin-film solar cell can exhibit an implied photo-current density equal to 41.1 mA/cm2, which is higher than that of a state-of-the-art wafer-based c-Si hetero-junction solar cell. This performance makes BaSi2 an attractive absorber for high-performing thin-film and multi-junction solar cells. In particular, to assess the potential of barium di-silicide, we propose a thin-film double-junction solar cell based on organometallic halide perovskite (CH3NH3PbI3) as top absorber and BaSi2 as bottom absorber. The resulting modelled ultra-thin double-junction CH3NH3PbI3 / BaSi2 (< 2 μm) exhibits an implied total photo-current density equal to 38.65 mA/cm2 (19.84 mA/cm2 top cell, 18.81 mA/cm2 bottom cell) and conversion efficiencies up to 28%.

  3. Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome

    PubMed Central

    Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva

    2015-01-01

    A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0–120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome. PMID:26783479

  4. Misaligned Spin and Orbital Axes Cause the Anomalous Precession of DI Herculis

    NASA Technical Reports Server (NTRS)

    Albrecht, Simon; Reffert, Sabine; Snellen, Ignas A. G.; Winn, Joshua N.

    2009-01-01

    In this case we applied our Rossiter-McLaughlin methodology to a binary star, rather than a star-planet system. The orbits of binary stars precess as a result of general relativistic effects, forces arising from the asphericity of the stars, and forces from any additional stars or planets in the system. For most binaries, the theoretical and observed precession rates are in agreement. However, one system known as DI Herculis has resisted explanation for 30 years. The observed precession rate is a factor of four slower than the theoretical rate, a disagreement that once was interpreted as evidence for a failure of general relativity. Among the contemporary explanations are the existence of a circumbinary planet and a large tilt of the stellar spin axes with respect to the orbit. In this paper we reported that both stars of DI Herculis rotate with their spin axes nearly perpendicular to the orbital axis (contrary to the usual assumption for close binary stars). The rotationally induced stellar oblateness causes precession in the direction opposite to that of relativistic precession, thereby reconciling the theoretical and observed rates.

  5. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence.

    PubMed

    Davies, Bryan W; Bogard, Ryan W; Young, Travis S; Mekalanos, John J

    2012-04-13

    The function of the Vibrio 7(th) pandemic island-1 (VSP-1) in cholera pathogenesis has remained obscure. Utilizing chromatin immunoprecipitation sequencing and RNA sequencing to map the regulon of the master virulence regulator ToxT, we identify a TCP island-encoded small RNA that reduces the expression of a previously unrecognized VSP-1-encoded transcription factor termed VspR. VspR modulates the expression of several VSP-1 genes including one that encodes a novel class of di-nucleotide cyclase (DncV), which preferentially synthesizes a previously undescribed hybrid cyclic AMP-GMP molecule. We show that DncV is required for efficient intestinal colonization and downregulates V. cholerae chemotaxis, a phenotype previously associated with hyperinfectivity. This pathway couples the actions of previously disparate genomic islands, defines VSP-1 as a pathogenicity island in V. cholerae, and implicates its occurrence in 7(th) pandemic strains as a benefit for host adaptation through the production of a regulatory cyclic di-nucleotide.

  6. Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate

    PubMed Central

    Tanser, A. R.; Bourke, M. P.; Blandford, A. G.

    1973-01-01

    Tanser, A. R., Bourke, M. P., and Blandford, A. G. (1973).Thorax, 28, 596-600. Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate. We investigated 57 employees of a factory where diphenyl-methane di-isocyanate (MDI) was used to prepare the materials for making rigid polyurethane foam. Four employees had developed hypersensitivity to MDI. Two had severe, and one moderate asthma, while the fourth had symptoms resembling the delayed hypersensitivity type of reaction. Ten other employees had experienced unpleasant, mainly respiratory, irritant effects from MDI vapour. A past history of bronchitis or of allergy was found more commonly in those with symptoms from MDI than in those without symptoms. It is not known if MDI causes permanent damage to the respiratory tract. The most severely affected cases in the present series had normal spirometric values after recovery, and no persisting symptoms. MDI is safer than other isocyanates used in industry but may cause both major and minor illness. It should be handled with the same precautions as those used with the more toxic compounds. PMID:4784381

  7. Di-Isocyanate Crosslinked Aerogels with 1, 6-Bis (Trimethoxysilyl) Hexane Incorporated in Silica Backbone

    NASA Technical Reports Server (NTRS)

    Vivod, Stephanie L.; Meador, Mary Ann B.; Nguyen, Baochau N.; Quade, Derek; Randall, Jason; Perry, Renee

    2008-01-01

    Silica aerogels are desirable materials for many applications that take advantage of their light weight and low thermal conductivity. Addition of a conformal polymer coating which bonds with the amine decorated surface of the silica network improves the strength of the aerogels by as much as 200 times. Even with vast improvement in strength they still tend to undergo brittle failure due to the rigid silica backbone. We hope to increase the flexibility and elastic recovery of the silica based aerogel by altering the silica back-bone by incorporation of more flexible hexane links. To this end, we investigated the use of 1,6-bis(trimethoxysilyl)hexane (BTMSH), a polysilsesquioxane precursor3, as an additional co-reactant to prepare silica gels which were subsequently cross-linked with di-isocyanate. Previously, this approach of adding flexibility by BTMSH incorporation was demonstrated with styrene cross-linked aerogels. In our study, we varied silane concentration, mol % of silicon from BTMSH and di-isocyanate concentration by weight percent to attempt to optimize both the flexibility and the strength of the aerogels.

  8. Cardiovascular malformations in DiGeorge syndrome (congenital absence of hypoplasia of the thymus).

    PubMed Central

    Moerman, P; Goddeeris, P; Lauwerijns, J; Van der Hauwaert, L G

    1980-01-01

    Partial or complete absence of the thymus (DiGeorge syndrome, III-IV pharyngeal pouch syndrome) is often associated with agenesis or hypoplasia of the parathyroid glands and, almost invariably, with cardiovascular malformations. The clinical and pathologcial findings in 10 cases proven at necropsy are presented. All patients presented with cardiac symptoms and signs in the first weeks of life and, with one exception, all died of a cardiac cause. Major cardiovascular malformations were found in all 10 cases. Four had, in association with a ventricular septal defect of the infundibular type, an interrupted aortic arch, which was left-sided in two and right-sided in two other cases. Four patients had truncus arteriosus type I, in two of them associated with a right-sided aortic arch. Two patients with tetralogy of Fallot had a right-sided aortic arch. Only two of the 10 had a normally developed left aortic arch. Aberrant subclavian arteries were found in five cases. From our observations and a survey of the previously published patients it appears that 90 per cent of the necropsy-proven cases of DiGeorge syndrome have cardiovascular malformations and that 95 per cent of these malformations can be classified as aortic arch anomalies, truncus ateriosus, or tetralogy of Fallot. Images PMID:7426208

  9. Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome.

    PubMed

    Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva

    2015-01-01

    A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0-120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome. PMID:26783479

  10. Mono- and di-bromo platinum(IV) prodrugs via oxidative bromination: synthesis, characterization, and cytotoxicity.

    PubMed

    Xu, Zoufeng; Wang, Zhigang; Yiu, Shek-Man; Zhu, Guangyu

    2015-12-14

    Platinum(IV)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(IV) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(II) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(IV) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(IV) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(IV) prodrugs and provides with a convenient strategy to obtain brominated platinum(IV) complexes.

  11. Di-hydrogen contact induced lattice instabilities and structural dynamics in complex hydride perovskites.

    PubMed

    Schouwink, P; Hagemann, H; Embs, J P; D'Anna, V; Černý, R

    2015-07-01

    The structural phase transitions occurring in a series of perovskite-type complex hydrides based on the tetrahydroborate anion BH4(-) are investigated by means of in situ synchrotron x-ray powder diffraction, vibrational spectroscopy, thermal methods and ab initio calculations in the solid state. Structural dynamics of the BH4 anion are followed with quasi-elastic neutron scattering. We show that unexpected temperature-induced lattice instabilities in perovskite-type ACa(BH4)3 (A = K, Rb, Cs) have their origin in close hydridic di-hydrogen contacts. The rich lattice dynamics lead to coupling between internal B-H vibrations and phonons, resulting in distortions in the high-temperature polymorph that are identical in symmetry to well-known instabilities in oxide perovskites, generally condensing at lower temperatures. It is found that anion-substitution BH4(-) <-> (X = Halide) can relax distortions in ACa(BH4)3 by eliminating coulomb repulsive H(-)···H(-) effects. The interesting nature of phase transition in ACa(BH4)3 enters an unexplored field of weak interactions in ceramic-like host lattices and is the principal motivation for this study. Close di-hydrogen contacts suggest new concepts to tailor crystal symmetries in complex hydride perovskites in the future. PMID:26076047

  12. A potential early middle Pleistocene tephrostratotype for the Mediterranean basin: the Vallo Di Diano, Campania, Italy

    NASA Astrophysics Data System (ADS)

    Karner, D. B.; Juvigne, E.; Brancaccio, L.; Cinque, A.; Russo Ermolli, E.; Santangelo, N.; Bernasconi, S.; Lirer, L.

    1999-07-01

    A 207-m-long core was taken from the deposits of a paleolake formed in the Vallo di Diano tectonic basin of the southern Apennines, Italy. Fourteen major tephra beds were identified and distributed into three groups based on stratigraphic position, and chemical and mineralogical compositions. In a pilot dating program, glass ages were determined for three of these layers using the 40Ar/ 39Ar method; two of those layers produced discordant step-heating spectra and provided anomalously old ages. A third layer produced a well-defined plateau age of 0.596±0.006 Ma (2 σ) and from its stratigraphic position, is correlated to oxygen isotope (δ 18O) stage 15 of the deep-sea record. The climatic history of the paleolake can be interpreted from down-core pollen and δ 18O variations, which show a succession of two glacial-interglacial cycles. Extrapolation of ages from the astronomically tuned deep-sea δ 18O record to that of the paleolake indicates that the lake existed for almost 0.2 Ma. Potential eruptive source regions for the tephra layers include the Roman Volcanic Province, Roccamonfina and perhaps Mt. Vulture. While further dating is needed, the Vallo di Diano section provides valuable information on Middle Pleistocene climate history for the central Mediterranean region and offers a comparison of terrestrial environmental history to those preserved in marine records.

  13. Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components.

    PubMed Central

    Rock, G; Labow, R S; Tocchi, M

    1986-01-01

    In order to impart flexibility, plastic medical devices incorporate liquid plasticizers into their structure. Data from several laboratories, including ours, have shown that these compounds leach from blood bags and tubing during collection of blood, storage of various blood components and during kidney dialysis and cell and plasma apheresis procedures. After the plasticizer di(2-ethylhexyl) phthalate leaches from poly(vinyl chloride) blood packs, it is converted by a plasma enzyme to a more toxic metabolite, mono(2-ethylhexyl) phthalate. Blood fractionation products from outdated plasma contain mono(2-ethylhexyl) phthalate, the highest level being found in normal serum albumin. Recently, we have reported that di(2-ethylhexyl) phthalate actually binds to the red blood cell membrane and reduces its osmotic fragility. Current methods of red cells storage, which permit utilization up to 35 days after collection, are not possible without this membrane stabilization. Platelets are now stored for 5 days in the Fenwal PL 732 polyolefin bag. Although stated to be essentially free of liquid plasticizers, a significant level of leaching from this bag into the extracts of stored platelet concentrates was observed. PMID:3709456

  14. X-ray Radiative Transfer in Protoplanetary Disks with ProDiMo

    NASA Astrophysics Data System (ADS)

    Rab, Christian; Woitke, Peter; Güdel, Manuel; Min, Michiel; Diana Team

    2013-07-01

    X-ray emission is a common property of YSOs. T Tauri stars show X-ray luminosities up to 10^32 erg/s but also Herbig Ae/Be stars can have moderate X-ray emission in the range of 10^28 to 10^31 erg/s. We want to investigate the impact of X-ray radiation on the thermal and chemical structure of protoplanetary discs around these YSOs. Therefore we have added a new X-ray Radiative Transfer module to the radiation thermo-chemical code ProDiMo (Protoplanetary Disc Modeling) extending the existing implementation of X-ray chemistry implemented by Aresu et al. This new module considers gas and dust opacities (including scattering) and a possible X-ray background field. Further we added a new set of FUV - photoreactions to the X-ray chemistry module of ProDiMo as fast electrons created in X-ray ionisation can produce a significant secondary FUV radiation field by exciting atomic or molecular hydrogen. We discuss the importance of these processes on the thermal and chemical structure of the protoplanetary disc, and present them on the basis of a typical T Tauri disc model. This work is performed in the context of the EU FP7-project DIANA (www.diana-project.com).

  15. Correlation functions for a di-neutron condensate in asymmetric nuclear matter

    NASA Astrophysics Data System (ADS)

    Isayev, A. A.

    2008-07-01

    Recent calculations with an effective isospin-dependent contact interaction show the possibility of the crossover from superfluidity of neutron Cooper pairs in the S10 pairing channel to Bose-Einstein condensation (BEC) of di-neutron bound states in dilute nuclear matter. The density and spin correlation functions are calculated for a di-neutron condensate in asymmetric nuclear matter with the aim of finding the possible features of the BCS-BEC crossover. It is shown that the zero-momentum transfer spin correlation function satisfies the sum rule at zero temperature. In symmetric nuclear matter, the density correlation function changes sign at low momentum transfer across the BCS-BEC transition, and this feature can be considered as a signature of the crossover. At finite isospin asymmetry, this criterion gives too large a value for the critical asymmetry αcd~0.9, at which the BEC state is quenched. Therefore, it can be trusted for the description of the density-driven BCS-BEC crossover of neutron pairs only at small isospin asymmetry. This result generalizes the conclusion of the study in Phys. Rev. Lett. 95, 090402 (2005), where the change of sign of the density correlation function at low momentum transfer in two-component quantum fermionic atomic gas with the balanced populations of fermions of different species was considered as an unambiguous signature of the BCS-BEC transition.

  16. Probing a light CP-odd scalar in di-top-associated production at the LHC

    NASA Astrophysics Data System (ADS)

    Casolino, Mirkoantonio; Farooque, Trisha; Juste, Aurelio; Liu, Tao; Spannowsky, Michael

    2015-10-01

    CP-odd scalars are an integral part of many extensions of the Standard Model. Recently, electroweak-scale pseudoscalars have received increased attention in explaining the diffuse gamma-ray excess from the Galactic Centre. Elusive due to absence of direct couplings to gauge bosons, these particles receive only weak constraints from direct searches at LEP or searches performed during the first LHC runs. We investigate the LHC's sensitivity in probing a CP-odd scalar in the mass range 20 ≤ m_A ≤ 100 GeV via di-top-associated production using jet-substructure-based reconstruction techniques. We parameterise the scalar's interactions using a simplified model approach and relate the obtained upper limits to couplings within type-I and type-II 2HDMs as well as the NMSSM. We find that in di-top-associated production, experiments at the LHC can set tight limits on CP-odd scalars that fit the Galactic Centre excess. However, direct sensitivity to light CP-odd scalars from the NMSSM remains challenging.

  17. Short communication: Chemical and sensory characteristics of Canestrato di Moliterno cheese manufactured in spring.

    PubMed

    Trani, A; Gambacorta, G; Loizzo, P; Cassone, A; Faccia, M

    2016-08-01

    Canestrato di Moliterno is an Italian Protected Geographical Indication hard cheese, made in winter and spring from a mixture of ewe and goat milks, that has been poorly investigated. The present study was aimed at characterizing the cheese made in the warm season. Two series of samples, ripened in traditional rooms called fondaco as indicated in the official protocol of production, were taken from the main certified producers. The cheeses were analyzed for gross composition; proteolysis and lipolysis; volatile fraction; and organoleptic features. Gross composition was not completely homogeneous among the samples, but primary proteolysis and lipolysis were quite uniform. We observed variations in secondary proteolysis, likely caused by fluctuations in environmental conditions in the fondaco. The sensory profiles of the samples were homogeneous: the cheese was soluble, greasy, and adhesive, with a sheepfold and buttery odor. The main taste attributes were fermented, pungent, and bitter. Overall, the results of this study provide an initial contribution to the characterization of Canestrato di Moliterno, and could be used to improve marketing strategies. PMID:27179855

  18. Short communication: Chemical and sensory characteristics of Canestrato di Moliterno cheese manufactured in spring.

    PubMed

    Trani, A; Gambacorta, G; Loizzo, P; Cassone, A; Faccia, M

    2016-08-01

    Canestrato di Moliterno is an Italian Protected Geographical Indication hard cheese, made in winter and spring from a mixture of ewe and goat milks, that has been poorly investigated. The present study was aimed at characterizing the cheese made in the warm season. Two series of samples, ripened in traditional rooms called fondaco as indicated in the official protocol of production, were taken from the main certified producers. The cheeses were analyzed for gross composition; proteolysis and lipolysis; volatile fraction; and organoleptic features. Gross composition was not completely homogeneous among the samples, but primary proteolysis and lipolysis were quite uniform. We observed variations in secondary proteolysis, likely caused by fluctuations in environmental conditions in the fondaco. The sensory profiles of the samples were homogeneous: the cheese was soluble, greasy, and adhesive, with a sheepfold and buttery odor. The main taste attributes were fermented, pungent, and bitter. Overall, the results of this study provide an initial contribution to the characterization of Canestrato di Moliterno, and could be used to improve marketing strategies.

  19. Comparison of stabilization by Vitamin E and 2,6-di-tert-butylphenols during polyethylene radio-thermal-oxidation

    NASA Astrophysics Data System (ADS)

    Richaud, Emmanuel

    2014-10-01

    This paper reports a compilation of data for PE+Vitamin E and 2,6-di-tert-butylphenols oxidation in radio-thermal ageing. Data unambiguously show that Vitamin E reacts with Prad and POOrad whereas 2,6-di-tert-butyl phenols only react with POOrad . Kinetic parameters of the stabilization reactions for both kinds of antioxidants were tentatively extracted from phenol depletion curves, and discussed regarding the structure of the stabilizer. They were also used for completing an existing kinetic model used for predicting the stabilization by antioxidants. This one permits to compare the efficiency of stabilizer with dose rate or sample thickness.

  20. Microbiota and metabolome of un-started and started Greek-type fermentation of Bella di Cerignola table olives.

    PubMed

    De Angelis, Maria; Campanella, Daniela; Cosmai, Lucrezia; Summo, Carmine; Rizzello, Carlo Giuseppe; Caponio, Francesco

    2015-12-01

    This study aimed to utilize an "omics" approach to evaluate the ability of selected lactobacilli and yeasts to improve the fermentation process of Bella di Cerignola table olives. Four types of fermentations were performed at the pilot-plant scale: un-started fermented olives used as a control (Ctrl); olives started with a commercial Lactobacillus plantarum strain (S); commercial L. plantarum strain and autochthonous yeast Wickeramomyces anomalus DiSSPA73 (SY); and L. plantarum, W. anomalus DiSSPA73, autochthonous L. plantarum DiSSPA1A7 and Lactobacillus pentosus DiSSPA7 (SYL). Compared to Ctrl, S, SY, SYL showed a higher acidification (P < 0.05) of the brine, which reached a pH value of 4.49 after one day of fermentation. The microbiota of unfermented olives and brine after one day of fermentation was primarily composed of Enterobacteria that belonged to Hafnia alvei and Methylobacterium. However, L. plantarum and L. pentosus dominated the total and metabolically active microbiota of the Ctrl brines and olives at the end of the fermentation. The use of lactobacilli and W. anomalus DiSSPA73 as a starter culture markedly affected the microbiota of the brines after one day of fermentation. The number of species (OTU) and the results of an alpha diversity analysis indicated that the microbial diversity of the brines was markedly simplified by the S, SY and, in particular, SYL fermentations. According to the lowest biodiversity, S, SY and SYL samples showed the lowest abundance of Proteobacteria, including Enterobacteriacea, Lactococcus lactis, Propionibacterium acidipropionici and Clostridium. The lactobacilli and W. anomalus DiSSPA73 used in this study markedly affected the amounts of free amino acids, phenolic and volatile organic compounds. Both a texture profile analysis and a sensory evaluation showed the highest appreciation for all of the started table olives. As shown through microbiological, biochemical, and sensory analyses, an accelerated

  1. Spectral and Non Radiative Decay Studies of Lead Di Bromide Single Crystals by Mode Matched Thermal Lens Technique.

    PubMed

    Rejeena, I; Lillibai, B; Thomas, V; Nampoori, V P N; Radhakrishnan, P

    2016-07-01

    In the present paper, the investigations on the non radiative decay mechanism, optical band gap determination from absorption spectroscopic studies and fluorescence emission by photo luminescence techniques using different excitation wavelengths on gel derived lead di bromide single crystals are reported. Non radiative decay of the sample is studied using high sensitive dual beam mode matched thermal lens technique. For the thermal lensing experiment the crystal in solution phase is incorporated with rhodamine 6G dye for enhancing the absorption of the crystal sample. The thermal diffusivity of lead di bromide is determined using the probe beam intensity v/s time measurements. PMID:27165040

  2. A c-di-GMP Effector System Controls Cell Adhesion by Inside-Out Signaling and Surface Protein Cleavage

    PubMed Central

    Newell, Peter D.; Boyd, Chelsea D.; Sondermann, Holger; O'Toole, George A.

    2011-01-01

    In Pseudomonas fluorescens Pf0-1 the availability of inorganic phosphate (Pi) is an environmental signal that controls biofilm formation through a cyclic dimeric GMP (c-di-GMP) signaling pathway. In low Pi conditions, a c-di-GMP phosphodiesterase (PDE) RapA is expressed, depleting cellular c-di-GMP and causing the loss of a critical outer-membrane adhesin LapA from the cell surface. This response involves an inner membrane protein LapD, which binds c-di-GMP in the cytoplasm and exerts a periplasmic output promoting LapA maintenance on the cell surface. Here we report how LapD differentially controls maintenance and release of LapA: c-di-GMP binding to LapD promotes interaction with and inhibition of the periplasmic protease LapG, which targets the N-terminus of LapA. We identify conserved amino acids in LapA required for cleavage by LapG. Mutating these residues in chromosomal lapA inhibits LapG activity in vivo, leading to retention of the adhesin on the cell surface. Mutations with defined effects on LapD's ability to control LapA localization in vivo show concomitant effects on c-di-GMP-dependent LapG inhibition in vitro. To establish the physiological importance of the LapD-LapG effector system, we track cell attachment and LapA protein localization during Pi starvation. Under this condition, the LapA adhesin is released from the surface of cells and biofilms detach from the substratum. This response requires c-di-GMP depletion by RapA, signaling through LapD, and proteolytic cleavage of LapA by LapG. These data, in combination with the companion study by Navarro et al. presenting a structural analysis of LapD's signaling mechanism, give a detailed description of a complete c-di-GMP control circuit—from environmental signal to molecular output. They describe a novel paradigm in bacterial signal transduction: regulation of a periplasmic enzyme by an inner membrane signaling protein that binds a cytoplasmic second messenger. PMID:21304920

  3. Efficient desymmetrization of 4,6-di-O-benzyl-myo-inositol by Lipozyme TL-IM.

    PubMed

    Vasconcelos, Marcela G; Briggs, Raissa H C; Aguiar, Lucia C S; Freire, Denise M G; Simas, Alessandro B C

    2014-03-11

    The enantioselective enzymatic desymmetrization of 4,6-di-O-benzyl-myo-inositol, a myo-inositol derivative, was effectively catalyzed by Thermomyces lanuginosus lipase (TL-IM). The product 1D-1-O-acetyl-4,6-di-O-benzyl-myo-inositol, a useful precursor to inositol phosphates, was obtained in excellent yield and enantiomeric excess. Through the investigation of the effects of solvent, biocatalyst load, and temperature, a more economical procedure resulted. The feasibility of biocatalyst reuse was also shown.

  4. Microbiota and metabolome of un-started and started Greek-type fermentation of Bella di Cerignola table olives.

    PubMed

    De Angelis, Maria; Campanella, Daniela; Cosmai, Lucrezia; Summo, Carmine; Rizzello, Carlo Giuseppe; Caponio, Francesco

    2015-12-01

    This study aimed to utilize an "omics" approach to evaluate the ability of selected lactobacilli and yeasts to improve the fermentation process of Bella di Cerignola table olives. Four types of fermentations were performed at the pilot-plant scale: un-started fermented olives used as a control (Ctrl); olives started with a commercial Lactobacillus plantarum strain (S); commercial L. plantarum strain and autochthonous yeast Wickeramomyces anomalus DiSSPA73 (SY); and L. plantarum, W. anomalus DiSSPA73, autochthonous L. plantarum DiSSPA1A7 and Lactobacillus pentosus DiSSPA7 (SYL). Compared to Ctrl, S, SY, SYL showed a higher acidification (P < 0.05) of the brine, which reached a pH value of 4.49 after one day of fermentation. The microbiota of unfermented olives and brine after one day of fermentation was primarily composed of Enterobacteria that belonged to Hafnia alvei and Methylobacterium. However, L. plantarum and L. pentosus dominated the total and metabolically active microbiota of the Ctrl brines and olives at the end of the fermentation. The use of lactobacilli and W. anomalus DiSSPA73 as a starter culture markedly affected the microbiota of the brines after one day of fermentation. The number of species (OTU) and the results of an alpha diversity analysis indicated that the microbial diversity of the brines was markedly simplified by the S, SY and, in particular, SYL fermentations. According to the lowest biodiversity, S, SY and SYL samples showed the lowest abundance of Proteobacteria, including Enterobacteriacea, Lactococcus lactis, Propionibacterium acidipropionici and Clostridium. The lactobacilli and W. anomalus DiSSPA73 used in this study markedly affected the amounts of free amino acids, phenolic and volatile organic compounds. Both a texture profile analysis and a sensory evaluation showed the highest appreciation for all of the started table olives. As shown through microbiological, biochemical, and sensory analyses, an accelerated

  5. Occurrence of Di-(2-ethylhexyl) adipate and phthalate plasticizers in samples of meat, fish, and cheese and their packaging films.

    PubMed

    Cao, Xu-Liang; Zhao, Wendy; Churchill, Robin; Hilts, Carla

    2014-04-01

    Di-(2-ethylhexyl) adipate (DEHA) and phthalates are commonly used as plasticizers to soften polyvinyl chloride products. Because both DEHA and certain phthalates have been identified as priority chemicals for assessment of human health risk under the Government of Canada's Chemicals Management Plan, a comprehensive targeted survey was conducted to investigate the occurrence of DEHA and eight phthalates (di-methyl phthalate, di-ethyl phthalate, di-n-butyl phthalate, di-iso-butyl phthalate, butyl benzyl phthalate, di-n-hexyl phthalate, d-(2-ethylhexyl) phthalate, and di-n-octyl phthalate) in a total of 118 samples of meat (beef, pork, and chicken), fish, and cheese packaged mostly in cling films. The eight phthalates were not detected in any of the food packaging, but DEHA was detected in most of the cling films, indicating that although DEHA-plasticized films (e.g., polyvinyl chloride film) are currently being used by most grocery stores, nonplasticized cling films such as polyethylene film, are also being used by some stores. DEHA was not detected in any of the 10 cheese samples packaged in nonplasticized rigid plastics but was detected in all 30 cheese samples packaged in DEHA-plasticized cling films at levels from 0.71 to 879 μg/g, with an average of 203 μg/g. Only DEHA was detected in the beef, pork, chicken, and fish samples packaged in DEHA-plasticized cling films but at considerably lower levels than those found in cheese, with averages of 6.3, 9.1, 2.5, and 5.9 μg/g, respectively. Among the eight phthalates, only di-(2-ethylhexyl) phthalate (DEHP) was detected in a few cheese samples at levels from 0.29 to 15 μg/g, with an average of 2.8 μg/g; these levels were very likely due to environmental contamination. Levels of DEHA found in most of the cheese samples from this study are above the European specific migration limit of 18 mg/kg for DEHA in food or food simulants, and levels of phthalates (i.e., DEHP) were low.

  6. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol...

  7. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol...

  8. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol...

  9. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1)...

  10. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1)...

  11. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal ether. 721.9516 Section... Substances § 721.9516 Siloxanes and silicones, 3- propyl Me, di-Me, reaction products with polyethylene..., reaction products with polyethylene-polypropylene glycol Bu glycidyl ether (PMN P-97-740; CAS No....

  12. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal ether. 721.9516 Section... Substances § 721.9516 Siloxanes and silicones, 3- propyl Me, di-Me, reaction products with polyethylene..., reaction products with polyethylene-polypropylene glycol Bu glycidyl ether (PMN P-97-740; CAS No....

  13. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal ether. 721.9516 Section... Substances § 721.9516 Siloxanes and silicones, 3- propyl Me, di-Me, reaction products with polyethylene..., reaction products with polyethylene-polypropylene glycol Bu glycidyl ether (PMN P-97-740; CAS No....

  14. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal ether. 721.9516 Section... Substances § 721.9516 Siloxanes and silicones, 3- propyl Me, di-Me, reaction products with polyethylene..., reaction products with polyethylene-polypropylene glycol Bu glycidyl ether (PMN P-97-740; CAS No....

  15. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal ether. 721.9516 Section... Substances § 721.9516 Siloxanes and silicones, 3- propyl Me, di-Me, reaction products with polyethylene..., reaction products with polyethylene-polypropylene glycol Bu glycidyl ether (PMN P-97-740; CAS No....

  16. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol...

  17. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol...

  18. The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS

    ERIC Educational Resources Information Center

    Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C.; Greaves-Lord, Kirstin

    2015-01-01

    The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3Di and ADOS, in 186 children referred to…

  19. Crystal structure of 2-amino-1,3-di­bromo-6-oxo-5,6-di­hydro­pyrido[1,2-a]quinoxalin-11-ium bromide monohydrate

    PubMed Central

    Faizi, Md. Serajul Haque; Parashchenko, Yuliia

    2015-01-01

    In the title hydrated salt, C12H8Br2N3O+·Br−·H2O, which was synthesized by the reaction of the pyridine derivative Schiff base N 1,N 4-bis­(pyridine-2-yl­methyl­ene)benzene-1,4-di­amine with bromine, the asymmetric unit contains a 2-amino-1,3-di­bromo-6-oxo-5,6-di­hydro­pyrido[1,2-a]quinoxalin-11-ium cation, with a protonated pyridine moiety, a bromide anion and a water mol­ecule of solvation. The cation is non-planar with the di­bromo-substituted benzene ring, forming dihedral angles of 24.3 (4) and 11.5 (4)° with the fused pyridine and pyrazine ring moieties, respectively. In the crystal, the cations are linked through a centrosymmetric hydrogen-bonded cyclic R 4 2(8) Br2(H2O)2 unit by N—H⋯Br, N—H⋯O and O—H⋯Br hydrogen bonds, forming one-dimensional ribbons extending along b, with the planes of the cations lying parallel to (100). PMID:26594504

  20. Crystal structure of creatininium 5-(2,4-di­nitro­phen­yl)-1,3-di­methyl­barbiturate monohydrate: a potential anti­convulsant agent

    PubMed Central

    Poornima Devi, Ponnusamy; Kalaivani, Doraisamyraja

    2016-01-01

    In the anion of the title hydrated mol­ecular salt, C4H8N3O+·C12H9N4O7 −·H2O [systematic name: 2-amino-1-methyl-4-oxo-4,5-di­hydro-1H-imidazol-3-ium 5-(2,4-di­nitro­phen­yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetra­hydro­pyrimidin-4-olate monohydrate], the 2,4-di­nitro­phenyl ring is inclined to the mean plane of the pyrimidine ring [r.m.s. deviation = 0.37 Å] by 43.24 (8)°. The five-membered ring of the creatininium cation (2-amino-1-methyl-4-oxo-4,5-di­hydro-1H-imidazol-3-ium) is essentially planar with an r.m.s. deviation of 0.015 Å. In the crystal, the anions and cations are linked via N—H⋯O hydrogen bonds, forming sheets parallel to the ab plane. The sheets are linked via O—H⋯O hydrogen bonds involving the water mol­ecule, forming a three-dimensional framework. Within the framework, there are C—H⋯O hydrogen bonds present. The title mol­ecular salt displays anti­convulsant and hypnotic activities. PMID:27308003

  1. Discovery of natural nicking endonucleases Nb.BsrDI and Nb.BtsI and engineering of top-strand nicking variants from BsrDI and BtsI.

    PubMed

    Xu, Shuang-Yong; Zhu, Zhenyu; Zhang, Penghua; Chan, Siu-Hong; Samuelson, James C; Xiao, Jianping; Ingalls, Debra; Wilson, Geoffrey G

    2007-01-01

    BsrDI and BtsI restriction endonucleases recognize and cleave double-strand DNA at the sequences GCAATG (2/0) and GCAGTG (2/0), respectively. We have purified and partially characterized these two enzymes, and analyzed the genes that encode them. BsrDI and BtsI are unusual in two respects: each cleaves DNA as a heterodimer of one large subunit (B subunit) and one small subunit (A subunit); and, in the absence of their small subunits, the large subunits behave as sequence-specific DNA nicking enzymes and only nick the bottom strand of the sequences at these respective positions: GCAATG (-/0) and GCAGTG (-/0). We refer to the single subunit, the bottom-strand nicking forms as 'hemidimers'. Amino acid sequence comparisons reveal that BsrDI and BtsI belong to a family of restriction enzymes that possess two catalytic sites: a canonical PD-X(n)-EXK and a second non-canonical PD-X(n)-E-X12-QR. Interestingly, the other family members, which include BsrI (ACTGG 1/-1) and BsmI/Mva1269I (GAATGC 1/-1) are single polypeptide chains, i.e. monomers, rather than heterodimers. In BsrDI and BtsI, the two catalytic sites are found in two separate subunits. Site-directed mutagenesis confirmed that the canonical catalytic site located at the N-terminus of the large subunit is responsible for the bottom-strand cleavage, whereas the non-canonical catalytic site located in the small subunit is responsible for hydrolysis of the top strand. Top-strand specific nicking variants, Nt.BsrDI and Nt.BtsI, were successfully engineered by combining the catalytic-deficient B subunit with wild-type A subunit. PMID:17586812

  2. Using Expansion Strategies in Making Untranslatable Areas of Poetry Translatable: Sa'di's Bustan as a Case in Point

    ERIC Educational Resources Information Center

    Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

    2014-01-01

    The purpose of this study was to explore poetry translatability and seek to see what the translators do to compensate those untranslatable areas of poetry. In doing so, the researchers chose a literary work, i.e., Bustan, by one of the well-known Iranian poets, that is, Sa'di (Wickens, 1990) and one of its translations, "The Bustan by Shaikh…

  3. Promoter-restricted H3 Lys 4 di-methylation is an epigenetic mark for monoallelic expression.

    PubMed

    Rougeulle, Claire; Navarro, Pablo; Avner, Philip

    2003-12-15

    Methylation of histone tails has been implicated in long-term epigenetic memory. Methylated H3 Lys 4 (K4) is a generally conserved mark for euchromatic, transcriptionally active regions, although the effect of this modification is likely also to depend on its distribution both within the euchromatic region and more specifically within a given gene. Here we describe a profile of H3K4 di-methylation that is specific for monoallelically expressed genes. Both X-linked genes subject to X-inactivation and autosomal imprinted genes have di-methylated H3K4 restricted to their promoter regions. In contrast, high levels of H3K4 di-methylation are found in both promoters and exonic parts of autosomal genes and of X-linked genes that escape X-inactivation. We suggest that this pattern of promoter restricted H3 Lys 4 di-methylation, already present in totipotent cells, is causally related to the long-term programming of allelic expression and provides an epigenetic mark for monoallelically expressed genes.

  4. The Shell Seeker: What Is the Quantity of Shell in the Lido di Venezia Sand? A Calibration DRIFTS Experiment

    ERIC Educational Resources Information Center

    Pezzolo, Alessandra De Lorenzi

    2011-01-01

    In this experiment, students are given a fanciful application of the standard addition method to evaluate the approximate quantity of the shell component in a sample of sand collected on the Lido di Venezia seashore. Several diffuse reflectance infrared Fourier transform (DRIFT) spectra are recorded from a sand sample before and after addition of…

  5. Accumulation of Mannosylglycerate and Di-myo-Inositol-Phosphate by Pyrococcus furiosus in Response to Salinity and Temperature

    PubMed Central

    Martins, L. O.; Santos, H.

    1995-01-01

    (sup13)C and (sup1)H nuclear magnetic resonance spectroscopy was used to identify and quantify organic solutes accumulated by the hyperthermophilic archaeon Pyrococcus furiosus in response to temperature and salinity. Di-myo-inositol-phosphate and 2-O-(beta)-mannosylglycerate were the major organic solutes accumulated in these cells. The total intracellular organic solutes increased significantly in response either to an increase in temperature or to an increase in salinity, but (beta)-mannosylglycerate accumulated mainly at high salinities, whereas the concentration of di-myo-inositol-phosphate increased dramatically at supraoptimal growth temperatures. Glutamate was present at concentrations detectable by nuclear magnetic resonance only in cells grown in low-salinity media. The intracellular levels of K(sup+) are clearly dependent on the salinity of the medium, and the concentrations of this cation are high enough to counterbalance the negative charges of (beta)-mannosylglycerate and di-myo-inositol-phosphate in the cell. The results presented here together with those previously reported for Pyrococcus woesei (S. Scholz, J. Sonnenbichler, W. Schafer, and R. Hensel, FEBS Lett. 306:239-242, 1992) strongly support a role for di-myo-inositol-phosphate in thermoprotection. PMID:16535119

  6. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM THE LE GRAY RESEARCH TEAM FOR NCEA June 15 2016

    EPA Science Inventory

    this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet.

  7. [Analysis on medication principles for cough based on experience of Xu Di-hua, descendant of Meng He Medical School].

    PubMed

    Xu, Xiao-jing; Xu, Li-min; Shen, Chun-feng; Wang, Cai-hua; Shen, Chun-ti

    2015-11-01

    Based on the software of traditional Chinese medicine inheritance support system (TCMISS), this article aims to analyze the experience and composition rules for cough from the descendant of Meng He Medical School, Xu Di-hua. The cough cases treated by Xu Di-hua were collected, and recorded into TCMISS (V2.0). Data mining methods such as Apriori algorithm and complex system entropy cluster were used to analyze the medication principles of Xu Di-hua for cough from pathogenesis and therapeutie aspects, and dig out the frequency of the herbs in prescription, core medicine and new combinations. The experience of curing cough from Professor Xu Di-hua were well found in the research. He is good at choosing prescriptions accurately, and pays attention to simultaneous use of cold and moisture drugs with combination of tonification and purgation. He is skilled in adding or reducing materia medica flexibly, as well as regulating lung to relieve cough and eliminating phlegm by clearing heat. PMID:27071274

  8. Preparation and Characterization of Di-, Tri-, and Tetranuclear Schiff Base Complexes Derived from Diamines and 3,4-Dihydroxybenzaldehyde

    PubMed Central

    Abdulghani, Ahlam Jameel; Khaleel, Asmaa Mohammed Noori

    2013-01-01

    A series of new di-, tri-, and tetranuclear Co(II) and Cu(II) complexes of three new diSchiff base ligands were synthesized by two different methods. The first method involved the synthesis of the three ligands from condensation reaction of 3,4-dihydroxybenzaldehyde (L′H2) with ethylenediamine (en), o-phenylenediamine (o-PD), or 4,5-dimethyl-1,2-phenylendiamine (DMPD) in a mole ratio of 2 : 1 followed by the reaction of the resulting Schiff bases ligands with Cu(II) or Co(II) ions in the presence of 2,2′-bipyridyl (L) to form the di- and trinuclear metal complexes. The second method involved the condensation of the copper complex LCu(II)L′ (L = 2,2′-bipyridyl, L′ = 4-formylbenzene-1,2-bis(olate)) with en, o-PD, or DMPD in a mole ratio of 2 : 1, respectively, followed by reaction with CuCl2 or Cu(ClO4)2 to form di-, tri-, and tetranuclear copper (II) complexes, respectively. The structures of the ligands and metal complexes were characterized by elemental analyses, NMR, and FTIR spectra. The geometries of metal complexes were suggested according to elemental analysis, electronic spectra, thermal analyses, atomic absorption, and magnetic moments and conductivity measurements. PMID:24453995

  9. Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP

    PubMed Central

    Chatterjee, Debashree; Cooley, Richard B; Boyd, Chelsea D; Mehl, Ryan A; O'Toole, George A; Sondermann, Holger

    2014-01-01

    Stable surface adhesion of cells is one of the early pivotal steps in bacterial biofilm formation, a prevalent adaptation strategy in response to changing environments. In Pseudomonas fluorescens, this process is regulated by the Lap system and the second messenger cyclic-di-GMP. High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. In this study, we elucidate the molecular basis of LapG regulation by LapD and reveal a remarkably sensitive switching mechanism that is controlled by LapD's HAMP domain. LapD appears to act as a coincidence detector, whereby a weak interaction of LapG with LapD transmits a transient outside-in signal that is reinforced only when cyclic-di-GMP levels increase. Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling. DOI: http://dx.doi.org/10.7554/eLife.03650.001 PMID:25182848

  10. A Bayes Factor Meta-Analysis of Recent Extrasensory Perception Experiments: Comment on Storm, Tressoldi, and Di Risio (2010)

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Morey, Richard D.; Province, Jordan M.

    2013-01-01

    Psi phenomena, such as mental telepathy, precognition, and clairvoyance, have garnered much recent attention. We reassess the evidence for psi effects from Storm, Tressoldi, and Di Risio's (2010) meta-analysis. Our analysis differs from Storm et al.'s in that we rely on Bayes factors, a Bayesian approach for stating the evidence from data for…

  11. Resonance Raman study of the A-band short-time photodissociation dynamics of 2,5-di-iodothiophene

    SciTech Connect

    Ruan Caibin; Zhu Hailin; Wang Huigang; Zheng Xuming; Phillips, David Lee

    2008-12-07

    Resonance Raman spectra were obtained for 2,5-di-iodothiophene in cyclohexane solution with excitation wavelengths in resonance with its A-band absorption. These spectra indicate that the Franck-Condon region photodissociation dynamics have multidimensional character with motion mostly along the nominal symmetric C{sub 2}C{sub 3}/C{sub 4}C{sub 5} stretch {nu}{sub 2} (1388 cm{sup -1}) of the thienyl ring and this is accompanied by motions along the nominal symmetric CSC stretch {nu}{sub 6} (640 cm{sup -1}), the nominal symmetric C-I stretch {nu}{sub 7} (187 cm{sup -1}), the nominal antisymmetric CSC stretch {nu}{sub 19} (728 cm{sup -1}), the nominal antisymmetric C{sub 2}C{sub 3}/C{sub 4}C{sub 5} stretch {nu}{sub 16} (1497 cm{sup -1}), the nominal C{sub 3}C{sub 4} stretch {nu}{sub 3} (1286 cm{sup -1}) and four other vibrational modes. A preliminary resonance Raman intensity analysis was done and the results for 2,5-di-iodothiophene were compared to previous results for 2-iodothiophene and di-iodomethane to discuss the mechanism of the symmetric breaking in the initial A-band photodissociation dynamics of 2,5-di-iodothiophene and 2-iodothiophene.

  12. Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

    PubMed

    Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

    2015-01-01

    Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent. PMID:26406092

  13. Cyclic di-GMP contributes to adaption and virulence of Bacillus thuringiensis through a riboswitch-regulated collagen adhesion protein.

    PubMed

    Tang, Qing; Yin, Kang; Qian, Hongliang; Zhao, Youwen; Wang, Wen; Chou, Shan-Ho; Fu, Yang; He, Jin

    2016-01-01

    Cyclic di-GMP is a ubiquitous second messenger that regulates diverse cellular processes in bacteria by binding to various protein or riboswitch effectors. In Bacillus thuringiensis BMB171, a c-di-GMP riboswitch termed Bc2 RNA resides in the 5'-untranslated region (5'-UTR) of an mRNA that encodes a collagen adhesion protein (Cap). The expression of cap was strongly repressed in parent strain BMB171 because of the presence of Bc2 RNA but was significantly promoted in the Bc2 RNA markerless deletion mutant. Bc2 RNA acts as a genetic "on" switch, which forms an anti-terminator structure to promote cap read-through transcription upon c-di-GMP binding. As a result, cap transcription was de-repressed under high c-di-GMP levels. Therefore, Bc2 RNA regulates cap expression using a repression/de-repression model. Bc2 RNA-regulated Cap was also found to be tightly associated with motility, aggregation, exopolysaccharide secretion, biofilm formation, and virulence of B. thuringiensis BMB171 against its host insect Helicoverpa armigera. PMID:27381437

  14. 40 CFR 721.7260 - Polymer of poly-ethylene-polyamine and alkanediol di-gly-cidyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of poly-ethylene-polyamine and alkanediol di-gly-cidyl ether. 721.7260 Section 721.7260 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.7260 Polymer of poly-ethylene-polyamine and...

  15. A Study of the Contribution from Non-Perturbative Effects to Di-jet Yields at Forward Rapidity

    NASA Astrophysics Data System (ADS)

    Poulsen, Anna; Chang, Zilong; Gagliardi, Carl; Gagliardi Team

    2015-10-01

    It is well known that the proton's spin is equal to ℏ/2, but its internal structure and the spin contributions made by its parton constituents, especially gluons, remain enigmatic. By studying asymmetric di-jets produced in polarized proton-proton collisions at forward rapidity, more information about the spin contribution of the gluon can be attained. Next-to-leading order perturbative QCD calculations indicate that measurements of di-jets at forward rapidity with transverse momenta of 5 and 8 GeV/c can provide valuable information regarding the gluon polarization. However these calculations do not include background contributions from initial state-radiation, underlying events and beam remnants that can create additional particles which appear in the detector as jets. In this study, PYTHIA simulations were used to analyze jets of stable final state hadrons. A simple procedure is found to reject the background. Most of the di-jets that remain can be matched to initial hard scattered partons with momentum fractions x2 of the order 10-3 and x1 of 0.4 or greater. These kinematics indicate that the remaining di-jets will provide relevant information about the gluon's polarization and lead to a better understanding of the proton's structure at the partonic level. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1263281.

  16. Systematic Nomenclature for GGDEF and EAL Domain-Containing Cyclic Di-GMP Turnover Proteins of Escherichia coli.

    PubMed

    Hengge, Regine; Galperin, Michael Y; Ghigo, Jean-Marc; Gomelsky, Mark; Green, Jeffrey; Hughes, Kelly T; Jenal, Urs; Landini, Paolo

    2016-01-01

    In recent years, Escherichia coli has served as one of a few model bacterial species for studying cyclic di-GMP (c-di-GMP) signaling. The widely used E. coli K-12 laboratory strains possess 29 genes encoding proteins with GGDEF and/or EAL domains, which include 12 diguanylate cyclases (DGC), 13 c-di-GMP-specific phosphodiesterases (PDE), and 4 "degenerate" enzymatically inactive proteins. In addition, six new GGDEF and EAL (GGDEF/EAL) domain-encoding genes, which encode two DGCs and four PDEs, have recently been found in genomic analyses of commensal and pathogenic E. coli strains. As a group of researchers who have been studying the molecular mechanisms and the genomic basis of c-di-GMP signaling in E. coli, we now propose a general and systematic dgc and pde nomenclature for the enzymatically active GGDEF/EAL domain-encoding genes of this model species. This nomenclature is intuitive and easy to memorize, and it can also be applied to additional genes and proteins that might be discovered in various strains of E. coli in future studies.

  17. Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with Diguanylate Cyclase.

    PubMed

    Fernicola, Silvia; Torquati, Ilaria; Paiardini, Alessandro; Giardina, Giorgio; Rampioni, Giordano; Messina, Marco; Leoni, Livia; Del Bello, Fabio; Petrelli, Riccardo; Rinaldo, Serena; Cappellacci, Loredana; Cutruzzolà, Francesca

    2015-10-22

    Cyclic di-GMP (c-di-GMP) is a widespread second messenger that plays a key role in bacterial biofilm formation. The compound's ability to assume multiple conformations allows it to interact with a diverse set of target macromolecules. Here, we analyzed the binding mode of c-di-GMP to the allosteric inhibitory site (I-site) of diguanylate cyclases (DGCs) and compared it to the conformation adopted in the catalytic site of the EAL phosphodiesterases (PDEs). An array of novel molecules has been designed and synthesized by simplifying the native c-di-GMP structure and replacing the charged phosphodiester backbone with an isosteric nonhydrolyzable 1,2,3-triazole moiety. We developed the first neutral small molecule able to selectively target DGCs discriminating between the I-site of DGCs and the active site of PDEs; this molecule represents a novel tool for mechanistic studies, particularly on those proteins bearing both DGC and PDE modules, and for future optimization studies to target DGCs in vivo.

  18. Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP.

    PubMed

    Chatterjee, Debashree; Cooley, Richard B; Boyd, Chelsea D; Mehl, Ryan A; O'Toole, George A; Sondermann, Holger

    2014-01-01

    Stable surface adhesion of cells is one of the early pivotal steps in bacterial biofilm formation, a prevalent adaptation strategy in response to changing environments. In Pseudomonas fluorescens, this process is regulated by the Lap system and the second messenger cyclic-di-GMP. High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. In this study, we elucidate the molecular basis of LapG regulation by LapD and reveal a remarkably sensitive switching mechanism that is controlled by LapD's HAMP domain. LapD appears to act as a coincidence detector, whereby a weak interaction of LapG with LapD transmits a transient outside-in signal that is reinforced only when cyclic-di-GMP levels increase. Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling.

  19. Cyclic di-GMP contributes to adaption and virulence of Bacillus thuringiensis through a riboswitch-regulated collagen adhesion protein.

    PubMed

    Tang, Qing; Yin, Kang; Qian, Hongliang; Zhao, Youwen; Wang, Wen; Chou, Shan-Ho; Fu, Yang; He, Jin

    2016-01-01

    Cyclic di-GMP is a ubiquitous second messenger that regulates diverse cellular processes in bacteria by binding to various protein or riboswitch effectors. In Bacillus thuringiensis BMB171, a c-di-GMP riboswitch termed Bc2 RNA resides in the 5'-untranslated region (5'-UTR) of an mRNA that encodes a collagen adhesion protein (Cap). The expression of cap was strongly repressed in parent strain BMB171 because of the presence of Bc2 RNA but was significantly promoted in the Bc2 RNA markerless deletion mutant. Bc2 RNA acts as a genetic "on" switch, which forms an anti-terminator structure to promote cap read-through transcription upon c-di-GMP binding. As a result, cap transcription was de-repressed under high c-di-GMP levels. Therefore, Bc2 RNA regulates cap expression using a repression/de-repression model. Bc2 RNA-regulated Cap was also found to be tightly associated with motility, aggregation, exopolysaccharide secretion, biofilm formation, and virulence of B. thuringiensis BMB171 against its host insect Helicoverpa armigera.

  20. Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production.

    PubMed

    Andrade, Warrison A; Firon, Arnaud; Schmidt, Tobias; Hornung, Veit; Fitzgerald, Katherine A; Kurt-Jones, Evelyn A; Trieu-Cuot, Patrick; Golenbock, Douglas T; Kaminski, Pierre-Alexandre

    2016-07-13

    Induction of type I interferon (IFN) in response to microbial pathogens depends on a conserved cGAS-STING signaling pathway. The presence of DNA in the cytoplasm activates cGAS, while STING is activated by cyclic dinucleotides (cdNs) produced by cGAS or from bacterial origins. Here, we show that Group B Streptococcus (GBS) induces IFN-β production almost exclusively through cGAS-STING-dependent recognition of bacterial DNA. However, we find that GBS expresses an ectonucleotidase, CdnP, which hydrolyzes extracellular bacterial cyclic-di-AMP. Inactivation of CdnP leads to c-di-AMP accumulation outside the bacteria and increased IFN-β production. Higher IFN-β levels in vivo increase GBS killing by the host. The IFN-β overproduction observed in the absence of CdnP is due to the cumulative effect of DNA sensing by cGAS and STING-dependent sensing of c-di-AMP. These findings describe the importance of a bacterial c-di-AMP ectonucleotidase and suggest a direct bacterial mechanism that dampens activation of the cGAS-STING axis. PMID:27414497