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Sample records for metodologie di elaborazione

  1. Elaborazione dei dati sperimentali

    NASA Astrophysics Data System (ADS)

    Dapor, M.; Ropele, M.

    L'analisi statistica dei dati sperimentali, la loro elaborazione ed una corretta stima degli errori sono conoscenze necessarie agli studenti di fisica, biologia, chimica, ingegneria e dei corsi di specializzazione tecnico-scientifici in cui a di laboratorio. Chi si occupa di problemi tecnici e di misure, per studio o per lavoro, deve possedere gli strumenti matematici di calcolo e di analisi necessari ad una corretta interpretazione dei dati sperimentali. Il testo fornisce in modo sintetico, chiaro ed esaustivo, tutte le nozioni e le conoscenze utili allo scopo.

  2. [Attenzione per i dettagli in genitori di nazionalità italiana di donne affette da anoressia nervosa: uno studio comparativo].

    PubMed

    Chinello, Alessandro; Zappa, Luigi; Pastori, Miriam; Crocamo, Cristina; Ricciardelli, Paola; Clerici, Massimo; Carrà, Giuseppe

    2017-01-01

    RIASSUNTO. Scopo. È noto come l'anoressia nervosa (AN) e il disturbo dello spetto autistico (ASD) condividano alcuni tratti, come la rigidità mentale e l'attenzione per i dettagli, che potrebbero essere diffusi a livello familiare. Questo studio ha lo scopo di confrontare la distribuzione di tratti autistici in genitori con figlie affette da disturbo alimentare ED (anoressia - AN o bulimia nervosa - BN) con genitori appartenenti a un gruppo di controllo. Metodi. Sono stati coinvolti 40 genitori con figlie affette da disturbo alimentare (60% con anoressia, 40% con bulimia nervosa) e 33 genitori di controllo. Tutti i genitori hanno compilato questionari specifici riguardanti il quoziente di spettro autistico (AQ) e le stime cognitive (CET). Inoltre, sono stati somministrati EAT-26 e SCL-90-R al fine di escludere la presenza di disturbi psichiatrici o alimentari nel gruppo sperimentale. Risultati. Le analisi su AQ mostrano una differenza tra i due gruppi per un tratto autistico specifico, evidenziando una riduzione significativa dell'attenzione per i dettagli nel gruppo sperimentale (ED), in particolare nei genitori di figlie affette da AN. Discussione. Questi dati suggeriscono una preferenza per un'elaborazione globale delle informazioni nei genitori AN in contrasto a quanto trovato in pazienti con AN. La presenza di aspetti depressivi, ansiosi e di disturbi alimentari è stata esclusa nei genitori nel gruppo sperimentale tramite SCL-90-R e EAT-26. Infine, la capacità di prendere decisioni, misurata dal CET, è stata esclusa dalle nostre analisi. Conclusione. Nei genitori con figlie affette da AN emerge una peculiare preferenza per un'elaborazione cognitiva globale, suggerendo il ruolo dell'attenzione per i dettagli come nuovo fattore da considerare nelle valutazione cliniche di pazienti con AN e nei loro familiari. Considerando i limiti dello studio, ulteriori approfondimenti in merito sono necessari.

  3. 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.

  4. 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.

  5. 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:

  6. [Progress in c-di-GMP inhibitors].

    PubMed

    Xiang, Xuwen; Liu, Xingyu; Tao, Hui; Cui, Zining; Zhang, Lianhui

    2017-09-25

    The cyclic dinucleotide c-di-GMP is known as an important second messenger in bacteria, which controls various important cellular processes, such as cell differentiation, biofilm formation and virulence factors production. It is extremely vital for the development of new antibacterial agents by virtue of blocking c-di-GMP signal conduction. Current research indicates that there are three potential targets for discovering new antibacterial agents based on c-di-GMP regulated signal pathway, which are c-di-GMP synthases, c-di-GMP degrading enzymes and c-di-GMP receptors. Herein, we review small molecules that have been developed to inhibit c-di-GMP related enzymes and indicate perspectives of c-di-GMP inhibitors.

  7. 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

  8. 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. © 2013 American Academy of Forensic Sciences.

  9. 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.

  10. Ambienti Circumstellari ed Interstellari di Supernovae di vario Tipo ed Applicazioni Astrofisiche

    NASA Astrophysics Data System (ADS)

    Boffi, Francesca R.

    Nella presente tesi vengono studiati gli ambienti circumstellari ed interstellari di supernovae (anche SNe; singolare SN) di vario tipo. In particolare si descrivono alcune applicazioni astrofisiche, relative a questi ambienti, che permettono di desumere informazioni sui sistemi stellari progenitori delle supernovae o di determinare le distanze a tali oggetti. L' emissione radio da supernovae, prodotta nell' ambiente circumstellare ad opera dell'interazione idrodinamica del gas di SN con l' ambiente circostante, puo' essere impiegata come mezzo di indagine del sistema di pre-supernova. In particolare si e' introdotta l'idea che tale emissione possa essere impiegata nel caso delle SNe di tipo Ia come test dei sistemi progenitori di tipo simbiotico. Il test e' stato effettuato sulla SN 1986G, per la quale avevamo ottenuto limiti superiori a lunghezze d'onda radio. Nel caso che un sistema simbiotico sia responsabile di una SN Ia, l'interazione tra l' ejecta e una shell circumstellare origina, in un'epoca molto prossima al massimo di luce, un'emissione radio rivelabile con strumenti tipo Very Large Array. Inoltre l'emissione radio fornisce informazioni circa gli stadi di pre-supernova nel caso di altri tipi di supernova. In questo lavoro di tesi vengono presentati i risultati ottenuti nel caso delle SNe di tipo II 1984E e 1986E. Queste due SNe non mostrano emissione radio: la prima, in prossimita del massimo ottico, stava interagendo con una shell circumstellare prodotta da un episodio di perdita di massa di breve durata in fase di pre-supernova; la seconda, invece e' la prima SN ``vecchia'' ad essere rivelata nell' ottico ma non nel radio (l' oggetto non ha ancora iniziato la fase di supernova remnant ed emette radiazione ottica prodotta ancora per interazione circumstellare). In ambiente circum-interstellare, gli echi di luce, prodotti dallo scattering della luce della supernova ad opera della polvere presente, possono essere utilizzati per determinare le distanze

  11. Severe dystrophy in DiGeorge syndrome.

    PubMed

    Rózsai, Barnabás; Kiss, Akos; Csábi, Györgyi; Czakó, Márta; Decsi, Tamás

    2009-03-21

    We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow's milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome.

  12. [Lo stile di attaccamento insicuro è un fattore di rischio di ridotta densità minerale ossea in donne in menopausa. Uno studio pilota].

    PubMed

    Niolu, Cinzia; Bianciardi, Emanuela; Di Lorenzo, Giorgio; Nicolai, Sara; Celi, Monica; Ribolsi, Michele; Pietropolli, Adalgisa; Ticconi, Carlo; Tarantino, Umberto; Siracusano, Alberto

    2016-01-01

    RIASSUNTO. Introduzione. La depressione maggiore (MD) e l'osteoporosi sono malattie ad alta prevalenza nel genere femminile, associate a morbosità e mortalità. Sebbene alcuni studi abbiano dimostrato un'associazione tra MD, ridotta densità minerale ossea (BMD) e osteoporosi, non sono stati chiariti i meccanismi causali. Lo stile di attaccamento insicuro è stato messo in relazione con la patogenesi e il decorso di malattie croniche come la MD e le malattie cardiovascolari. Obiettivo di questo studio pilota è esplorare la relazione tra MD e BMD. Si ipotizza che lo stile di attaccamento possa agire da mediatore. Metodi. Il campione è formato da 101 donne in menopausa, 49 con MD e 52 controlli sani. La diagnosi di MD è stata formulata con l'intervista clinica e la Beck Depression Inventory. Lo stile di attaccamento è stato esplorato usando il Relationship Questionnaire, la BMD con la Mineralometria Ossea Computerizzata con tecnica DXA (Dual energy X-ray Absorptiometry). Risultati. L'analisi univariata ha mostrato che le donne con MD avevano valori di BMD inferiori rispetto ai controlli sani. Nelle analisi di regressione multipla la MD non è emersa come predittore significativo di ridotta BMD. Lo stile di attaccamento insicuro "preoccupato" è risultato un predittore significativo di ridotta BMD in tutti i siti scheletrici misurati con la DXA: colonna vertebrale lombare (p=0,008) e segmenti femorali: "femoral neck" (p=0,011), "total hip" (p=0,002). Conclusioni. Questo è il primo studio che esplora il possibile ruolo di MD e stile di attaccamento sulla BMD. Lo stile di attaccamento è risultato un predittore di ridotta BMD, indipendentemente dalla MD. L'attaccamento insicuro potrebbe avere un ruolo nella patogenesi dell'osteoporosi anche indipendente dalla MD. Se questi risultati saranno confermati, gli interventi terapeutici focalizzati sullo stile di attaccamento potrebbero contribuire al miglioramento della comorbilità psichiatrica e medica legata all'osteoporosi.

  13. 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.

  14. Die Schokoladen-Diät

    NASA Astrophysics Data System (ADS)

    Ehrhardt, Matthias

    Schlankheitskuren sind einerseits ein soziales Phänomen, aber auch ein großer Zweig der Nahrungsmittelindustrie. Die Industrie bietet dabei verschiedene Produkte an, wie Diätlebensmittel, Nahrungsergänzungsmittel, Sportkleidung und -ausrüstung, Übungsvideos und -bücher, usw. Allerdings ist es bekanntermaßen sehr schwer, das einmal erreichte Wunschgewicht auch langfristig zu halten. Häufig tritt dabei der so genannte Jojo-Effekt auf, so dass man schließlich nach der Diät mehr wiegt als vorher.

  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. 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...

  17. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SANITIZERS Certain Adjuvants and Production Aids § 178.3940 Tetraethylene glycol di-(2-ethylhexoate). Tetraethylene glycol di-(2-ethylhexoate) containing not more than 22 parts per million ethylene and/or... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tetraethylene glycol di-(2-ethylhexoate). 178.3940...

  18. 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

  19. 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…

  20. 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

  1. 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

  2. Biopreservation of Fior di Latte cheese.

    PubMed

    Angiolillo, L; Conte, A; Zambrini, A V; Del Nobile, M A

    2014-09-01

    In this study a new biopreservation system consisting of an active sodium alginate coating containing Lactobacillus reuteri applied to Fior di Latte cheese was studied. The final aim was to extend cheese shelf life by the in situ production of reuterin. Experimental trials were carried out with and without glycerol. How the fermentation time could improve the production of reuterin, enabling Fior di Latte shelf life, was also assessed. To this aim, the experimental analyses were conducted in 2 different trials, using 2 different production batches of samples. In the first one, Fior di Latte samples were dipped into the active sodium alginate solution prepared on the same day of their production, whereas in the second trial, samples were dipped into the active solution prepared 48h before their production to allow a proper fermentation of the inoculated microorganism. Microbiological and sensory quality indices were monitored to prove the effectiveness of biopreservation on product quality during storage. In the first trial, the combination of the probiotic microorganism with glycerol improved the microbial quality by 1 d compared with the same active solution without glycerol, whereas the 48-h-fermented active alginate solution (second trial) showed a further improved microbial quality. The application of an active coating enriched with L. reuteri and glycerol to Fior di Latte cheese is an optimal and innovative way to preserve the product and at the same time, with a combination of an optimal fermentation time, to prolong its microbial quality and thus its shelf life.

  3. 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.

  4. [Research strategies and application of reference Dao-di herbs].

    PubMed

    Yuan, Yuan; Chen, Ti-Ying; Huang, Lu-Qi; Jin, Yan; Yang, Jian; Zhao, Yu-Yang

    2017-07-01

    Establishing evaluation system of Dao-di herbs has been a problem to be solved in the field of traditional Chinese medicine (TCM), and is also a difficult problem in restricting the realization of TCM quality. On the basis of national drug standard substance requirements, this paper puts forward to set up reference Dao-di herbs in the first step of the evaluation system of Dao-di herbs, and discusses the properties, evaluation index system and its development requirements of reference Dao-di herbs, aiming at supporting the modern research and characteristics identification of Dao-di herbs in the future. Copyright© by the Chinese Pharmaceutical Association.

  5. [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.

  6. Studio delle popolazioni di blazar ad alte energie

    NASA Astrophysics Data System (ADS)

    Gasparrini, D.; Giommi, P.

    2008-10-01

    Utilizzando la grande quantita' di dati sui blazar disponibile ad oggi, e' possibile costruire una distribuzione spettrale di energia (SED) media per ciascuna classe di oggetti. Basandosi su un modello SSC, e' inoltre possibile stimare il comportamento di questi oggetti nella banda di energia dei raggi gamma partendo dalle informazioni ottenute da osservazioni in altre bande di energia quali il radio e l'X. Utilizzando le simulazioni sara` possibile prevedere un eventuale cambio di popolazione dominante ad alte energie(oltre 1GeV) rispetto a quanto avviene in banda radio dove domina la popolazione dei FSRQ rispetto ai BL Lac e cercare un'eventuale conferma dagli esperimenti AGILE e GLAST.

  7. Toluidine blue-O is a Nissl bright-field counterstain for lipophilic fluorescent tracers Di-ASP, DiI and DiO.

    PubMed

    Chelvanayagam, D K; Beazley, L D

    1997-03-01

    The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.

  8. 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

  9. 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.

  10. Design type air engine Di Pietro

    NASA Astrophysics Data System (ADS)

    Zwierzchowski, Jaroslaw

    The article presents a pneumatic engine constructed by Angelo Di Pietro. 3D solid models of pneumatic engine components were presented therein. A directional valve is a key element of the control system. The valve functions as a camshaft distributing air to particular engine chambers. The construction designed by Angelo Di Pietro is modern and innovative. A pneumatic engine requires low pressure to start rotary movement. With the use of CFD software, the fields of velocity vectors' distribution were determined. Moreover, the author determined the distribution of pressure values in engine inlet and outlet channels. CFD model studies on engine operation were conducted for chosen stages of operating cycles. On the basis of simulation tests that were conducted, the values of flow rates for the engine were determined. The distribution of pressure values made it possible to evaluate the torque value on the rotating shaft.

  11. [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).

  12. Di-hadron production at Jefferson Laboratory

    NASA Astrophysics Data System (ADS)

    Anefalos Pereira, Sergio; CLAS Collaboration

    2015-04-01

    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. Pair of hadrons (di-hadron) SIDIS provides information on the nucleon structure and hadronization dynamics that complements single-hadron SIDIS. The study of di-hadrons allow us to study higher twist distribution functions and Dihadron Fragmentation Functions (DiFF). Together with the twist-2 PDFs (f 1, g 1, h 1), 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 direct and unique insights 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 beam-, target- and double-spin asymmetries will be presented.

  13. Cyclic di-nucleotide signaling enters the eukaryote domain.

    PubMed

    Schaap, Pauline

    2013-11-01

    Cyclic (c-di-GMP) is the prevalent intracellular signaling 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) signaling 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 signaling. 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.

  14. Cyclic Di-AMP Impairs Potassium Uptake Mediated by a Cyclic Di-AMP Binding Protein in Streptococcus pneumoniae

    PubMed Central

    Bai, Yinlan; Yang, Jun; Zarrella, Tiffany M.; Zhang, Yang; Metzger, Dennis W.

    2014-01-01

    Cyclic di-AMP (c-di-AMP) has been shown to play important roles as a second messenger in bacterial physiology and infections. However, understanding of how the signal is transduced is still limited. Previously, we have characterized a diadenylate cyclase and two c-di-AMP phosphodiesterases in Streptococcus pneumoniae, a Gram-positive pathogen. In this study, we identified a c-di-AMP binding protein (CabP) in S. pneumoniae using c-di-AMP affinity chromatography. We demonstrated that CabP specifically bound c-di-AMP and that this interaction could not be interrupted by competition with other nucleotides, including ATP, cAMP, AMP, phosphoadenylyl adenosine (pApA), and cyclic di-GMP (c-di-GMP). By using a bacterial two-hybrid system and genetic mutagenesis, we showed that CabP directly interacted with a potassium transporter (SPD_0076) and that both proteins were required for pneumococcal growth in media with low concentrations of potassium. Interestingly, the interaction between CabP and SPD_0076 and the efficiency of potassium uptake were impaired by elevated c-di-AMP in pneumococci. These results establish a direct c-di-AMP-mediated signaling pathway that regulates pneumococcal potassium uptake. PMID:24272783

  15. [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.

  16. Identification of rice Di19 family reveals OsDi19-4 involved in drought resistance.

    PubMed

    Wang, Lili; Yu, Changchun; Chen, Cong; He, Chunlan; Zhu, Yingguo; Huang, Wenchao

    2014-12-01

    The OsDi19 proteins functioned as transcription factors and played crucial roles in response to abiotic stress. Overexpression of OsDi19-4 in rice increased drought tolerance by enhancing ROS-scavenging activity. Many transcription factors play crucial roles in plant responses to abiotic stress. Here, comprehensive sequence analysis suggested that the drought-induced 19 (Di19) gene family in rice genome contain seven members, and these proteins contained a well-conserved zinc-finger Di19 domain. Most OsDi19 proteins were mainly targeted to the nucleus and have transactivation activity in yeast. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that most OsDi19 proteins could form protein dimers. Expression analysis demonstrated that the OsDi19 genes were differentially and abundantly expressed in vegetative tissues, but expressed little in reproductive tissues and some of the OsDi19 genes were markedly induced by abiotic stresses and hormones in qRT-PCR analysis and microarray data. Overexpression of one stress-responsive gene, OsDi19-4, in rice resulted in significantly increased tolerance to drought stress compared with the wild type plants. Moreover, obviously increased ROS-scavenging ability was detected in the OsDi19-4-overexpressing plants under normal and drought stress conditions. These results suggested that the increased stress tolerance of OsDi19-4-overexpressing plants may be attributable to the enhanced ROS-scavenging activity. Taken together, these studies provide a detailed overview of the rice Di19 gene family, and suggest that the OsDi19 family may play crucial roles in the plant response to abiotic stress.

  17. 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

  18. Thermal and optical studies of some di-methyl-di-alkyl ammonium bromides

    NASA Astrophysics Data System (ADS)

    Witko, Waclaw; Godlewska, Malgorzata; Dynarowicz, Patrycja

    1998-01-01

    Phase situation of homologous series of di-alkyl-di-methyl ammonium bromides represented by the general formula: 2CnN+2C1Br-, with n equals 10, 12, 14, 16, 18, was investigated by means of differential scanning calorimetry and optical microscopy methods in the temperature range 20-180 degrees C. A more complex polymorphism as already reported was detected. All the compounds studied show at least tow anomalies on the DSC curves. The high-temperature phase which appears below the isotropic phase has lancet-like dendritic texture which can be attributed to SmB phase. The enthalpy changes at the transitions were calculated.

  19. DI: An interactive debugging interpreter for applicative languages

    SciTech Connect

    Skedzielewski, S.K.; Yates, R.K.; Oldehoeft, R.R.

    1987-03-12

    The DI interpreter is both a debugger and interpreter of SISLAL programs. Its use as a program interpreter is only a small part of its role; it is designed to be a tool for studying compilation techniques for applicative languages. DI interprets dataflow graphs expressed in the IF1 and IF2 languages, and is heavily instrumented to report the activity of dynamic storage activity, reference counting, copying and updating of structured data values. It also aids the SISAL language evaluation by providing an interim execution vehicle for SISAL programs. DI provides determinate, sequential interpretation of graph nodes for sequential and parallel operations in a canonical order. As a debugging aid, DI allows tracing, breakpointing, and interactive display of program data values. DI handles creation of SISAL and IF1 error values for each data type and propagates them according to a well-defined algebra. We have begun to implement IF1 optimizers and have measured the improvements with DI.

  20. Absent Aortic Valve in DiGeorge Syndrome.

    PubMed

    Bertsch, Elizabeth C; Minturn, Lucy; Gotteiner, Nina L; Ernst, Linda M

    2016-01-01

    A 20-week-old fetus with the 22q11.2 deletion characteristic of DiGeorge syndrome is described with vertebral segmentation abnormalities and complex cardiovascular anomalies including an absent aortic valve. This is only the second known case of absent aortic valve in association with DiGeorge syndrome. We discuss the association of absent aortic valve with other conotruncal defects and the utility of fetal echocardiography in the diagnosis of DiGeorge syndrome.

  1. 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

  2. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    PubMed

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense, c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state.IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates

  3. DBU-catalyzed transprotection of N-Fmoc-cysteine di- and tripeptides into S-Fm-cysteine di- and tripeptides.

    PubMed

    Katritzky, Alan R; Abo-Dya, Nader E; Abdelmajeid, Abdelmotaal; Tala, Srinivasa R; Amine, M S; El-Feky, Said A

    2011-01-21

    The transprotection of N-Fmoc-cysteine containing di- and tripeptides possessing a free SH group to produce the corresponding S-Fm-cysteine di- and tripeptides bearing a free amino group is accomplished efficiently with DBU in dry THF. The N-Fmoc to S-Fm transformation mechanism is discussed. S-Fm-Cysteine di- and tripeptides readily form amide bonds on coupling with N-(Pg-α-aminoacyl)benzotriazoles and N-(Pg-α-dipeptidoyl)benzotriazoles to give larger peptides.

  4. 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.

  5. Production of aromatics from di- and polyoxygenates

    DOEpatents

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

    2017-07-04

    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.

  6. 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.

  7. 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.

  8. 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

  9. A new di-O-prenylated isoflavone from Tephrosia tinctoria.

    PubMed

    Khalivulla, Shaik Ibrahim; Reddy, Bandi Anil Kumar; Gunasekar, Duvvuru; Blond, Alain; Bodo, Bernard; Murthy, Madugula Marthanda; Rao, Tadikimalli Prabhakar

    2008-01-01

    A new di-O-prenylated isoflavone, 5,7-di-O-prenylbiochanin A (1), together with three known compounds, 7-O-methylglabranin (2), tephrowatsin C (3) and flemichapparin B (4), were isolated from the stems of Tephrosia tinctoria. The structures of these compounds were elucidated by extensive 2D NMR spectral studies.

  10. What's in a Diary? Di-EL First Words

    ERIC Educational Resources Information Center

    Nott, Pauline; Brown, P. Margaret; Cowan, Rogert; Wigglesworth, Gillian

    2005-01-01

    Children with hearing loss and their families are now presenting for early intervention support and guidance at increasingly younger ages. At present there is a paucity of research that informs teachers about early language development in the child with hearing loss. Di-EL First Words (Di-EL) is a diary technique through which parents record their…

  11. 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.

  12. 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.

  13. Sul foro nella stanza di Nicola Cusano al castello di Andraz: un'ipotesi astronomica

    NASA Astrophysics Data System (ADS)

    de Donà, G.

    2011-02-01

    Nicolas Krebs (Kues 1401 - Todi 1464), also called Nicola Cusano, or Nicholas of Cusa - reached the Castello di Andraz (BL, Italy), where he lived for a long period. In a wall of his room there is a hole representing a possible astronomical function. In this paper, the author illustrates the orientation of the hole and suggests that it is been created by the great German thinker to correct the Julian calendar.

  14. 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.

  15. Limb anomalies in DiGeorge and CHARGE syndromes

    SciTech Connect

    Prasad, C.; Quackenbush, E.J.; Whiteman, D.; Korf, B.

    1997-01-20

    Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with CHARGE syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with CHARGE syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies. 14 refs., 4 figs.

  16. Identification of c-di-GMP-Responsive Riboswitches.

    PubMed

    Peltier, Johann; Soutourina, Olga

    2017-01-01

    Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important signaling molecule for community behavior control, cell morphogenesis, and virulence in bacteria. In addition to protein effectors, this second messenger binds RNA molecules that act as riboswitches to control target gene expression. In this chapter, we describe a method for experimental validation of the functionality of c-di-GMP-responsive riboswitches and the analysis of c-di-GMP control of target gene expression by qRT-PCR and Northern blot. This procedure can be used for the studies of in silico-predicted riboswitch candidates, as well as a targeted experimental approach for exploring the data from next-generation sequencing. The examples on the analysis of type I and type II c-di-GMP-responsive riboswitches in Clostridium difficile are provided to illustrate the application of the method.

  17. Vibrational frequencies and structural determinations of di-vinyl sulfone

    NASA Astrophysics Data System (ADS)

    Ellzy, Michael W.; Jensen, James O.; Kay, Jack G.

    2003-03-01

    We present a detailed analysis of the structure and infrared spectra of di-vinyl sulfone. The vibrational frequencies of the di-vinyl sulfone molecule were analyzed using standard quantum chemical techniques. Frequencies were calculated at the MP2 and DFT levels of theory using the standard 6-311G* basis set. The structural transformation of the chemical agent bis(2-chloroehtyl) sulfide (HD, mustard gas) and the related symmetry to a previously study compounds [Spectrochim. Acta Part A 55 (1999) 121; Spectrochim. Acta Part A 57 (2001) 2417] makes the symmetry of the di-vinyl sulfone molecule an interesting candidate for study. The molecule exists normally in a C2 configuration. High-energy forms of di-vinyl sulfone with CS and C1 symmetries also exist.

  18. 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.

  19. 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.

  20. [Structure and function of c-di-GMP riboswitches].

    PubMed

    Li, Xinfeng; Chen, Fang; Xiao, Jinfeng; He, Jin

    2017-09-25

    Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous nucleotide second messenger present in a wide variety of bacteria. It regulates many important bacterial physiological functions such as biofilm formation, motility, adhesion, virulence and extracellular polysaccharide synthesis. It binds with many different proteins or RNA receptors, one of which is called riboswitch that is usually located at the 5'-untranslational region (5'-UTR) in some mRNA. Riboswitch usually comprises a specific ligand-binding (sensor) domain (named aptamer domain, AD), as well as a variable domain, termed expression platform (EP), to regulate expression of downstream coding sequences. When a specific metabolite concentration exceeds its threshold level, it will bind to its cognate riboswitch receptor to induce a conformational change of 5'-UTR, leading to modulation of downstream gene expression. Two classes of c-di-GMP-binding riboswitches (c-di-GMP-Ⅰ and c-di-GMP-Ⅱ) have been discovered that bind with this second messenger with high affinity to regulate diverse downstream genes, underscoring the importance of this unique RNA receptor in this pathway. Class Ⅰ c-di-GMP riboswitches are present in a wide variety of bacteria, and are most common in the phyla Firmicutes and Proteobacteria, while class Ⅱ c-di-GMP riboswitches typically function as allosteric ribozymes, binding to c-di-GMP to induce folding changes at atypical splicing site junctions to modulate downstream gene expression. This review introduces the discovery, classification, function, and also the affected downstream genes of c-di-GMP riboswitches.

  1. Divertor materials evaluation system (DiMES)

    SciTech Connect

    Wong, C.P.C.; West, W.P.; Whyte, D.G.; Bastasz, R.J.; Brooks, J.; Wampler, W.R.

    1997-12-31

    The mission of the Divertor Materials Evaluation System (DiMES) in DIII-D is to establish an integrated data base from measurements in the divertor of a tokamak in order to address some of the ITER and fusion power reactor plasma material interaction issues. Carbon and metal coatings of Be, W, V, and Mo were exposed to the steady-state outer strike point on DIII-D for 4--18 s. These short exposure times ensure controlled exposure conditions, and the extensive arrays of DIII-D divertor diagnostics provide a well-characterized plasma for modeling efforts. Post-exposure analysis provides a direct measure of surface material erosion rates and the amount of retained deuterium. For carbon, these results match closely with the results of accumulated carbon deposition and erosion, and the corresponding deuterium retention of long term exposure tiles in DIII-D. Under the carbon-contaminated background plasma of DIII-D, metal coatings of Be, V, Mo, and W were exposed to the steady-state outer strike point under ELMing and ELM-free H-mode discharges. The rate of material erosion and deuterium retention were measured. As expected, W shows the lowest erosion rate at 0.1 mm/s and the lowest deuterium uptake of 2 {times} 10{sup 20}/m{sup 2}.

  2. Metabolite and mineral profiling of "Violetto di Niscemi" and "Spinoso di Menfi" globe artichokes by (1)H-NMR and ICP-MS.

    PubMed

    Albergamo, Ambrogina; Rotondo, Archimede; Salvo, Andrea; Pellizzeri, Vito; Bua, Daniel G; Maggio, Antonella; Cicero, Nicola; Dugo, Giacomo

    2017-05-01

    Globe artichoke has been long considered a nutraceutical food for its valuable content of bioactive compounds. However, beside a well-known polyphenol profile, poor information is available about its metabolite and mineral composition. The aim of this study was to investigate edible parts of Sicilian artichokes, 'Spinoso di Menfi' and 'Violetto di Niscemi', by (1)H NMR and ICP-MS for elucidating these compositional aspects. Although bracts and hearts of both artichokes shared a very similar metabolite pattern, 'Spinoso di Menfi' showed a higher number of metabolites, such as amino acids and polyphenols, than 'Violetto di Niscemi'. 'Spinoso di Menfi' was also marked by higher levels of macro- and microelements when compared to 'Violetto di Niscemi'. Also, artichoke heart demonstrated to accumulate higher mineral levels than bracts. (1)H NMR and ICP-MS successfully profiled metabolites and metals in such plant food, partially covering the lack of literature data about 'Spinoso di Menfi' and 'Violetto di Niscemi' artichokes.

  3. 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

  4. 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.

  5. An experiment of formation of charmoni states in annihilation P-Pbarra. Un esperimento di formazione di stati del charmonio in annichilazione P-Pbarra

    SciTech Connect

    Pallavicini, Marco

    1995-01-01

    Oggetto di questa tesi e la misura di alcune caratteristiche fisiche (massa, larghezza, e larghezza parziale in p - $\\bar{p}$) degli stati 3P1 e 3P2 del charmonio, -ovvero del sistema legato di un quark "charm" e del suo antiquark-, nell'amito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab.

  6. CUB DI (Deionization) column control system

    SciTech Connect

    K. C. Seino

    1999-07-02

    For the old MR (Main Ring), deionization was done with two columns in CUB, using an ion exchange process. Typically 65 GPM of LCW flew through a column, and the resistivity was raised from 3 Mohm-cm to over 12 Mohm-cm. After a few weeks, columns lost their effectiveness and had to be regenerated in a process involving backwashing and adding hydrochloric acid and sodium hydroxide. For normal MR operations, LCW returned from the ring and passed through the two columns in parallel for deionization, although the system could have been operated satisfactorily with only one in use. A 3000 gallon reservoir (the Spheres) provided a reserve of LCW for allowing water leaks and expansions in the MR. During the MI (Main Injector) construction period, the third DI column was added to satisfy requirements for the MI. When the third column was added, the old regeneration controller was replaced with a new controller based on an Allen-Bradley PLC (i.e., SLC-5/04). The PLC is widely used and well documented, and therefore it may allow us to modify the regeneration programs in the future. In addition to the above regeneration controller, the old control panels (which were used to manipulate pumps and valves to supply LCW in Normal mode and to do Int. Recir. (Internal Recirculation) and Makeup) were replaced with a new control system based on Sixtrak Gateway and I/O modules. For simplicity, the new regeneration controller is called as the US Filter system, and the new control system is called as the Fermilab system in this writing.

  7. Divertor Materials Evaluation System (DiMES)

    SciTech Connect

    Wong, C.P.; West, W.P.; Whyte, D.G.; Bastasz, R.J.; Brooks, J.; Wampler, W.R.

    1997-11-01

    The mission of the Divertor Materials Evaluation System (DiMES) in DIII-D is to establish an integrated data base from measurements in the divertor of a tokamak in order to address some of the ITER and fusion power reactor plasma material interaction issues. Carbon and metal coatings of Be, W, V, and Mo were exposed to the steady-state outer strike point on DIII-D for 4-18 s. These short exposure times ensure controlled exposure conditions, and the extensive arrays of DIII-D divertor diagnostics provide a well-characterized plasma for modeling efforts. Postexposure analysis provides a direct measure of surface material erosion rates and the amount of retained deuterium. For carbon, these results match closely with the results of accumulated carbon deposition and erosion, and the corresponding deuterium retention of long term exposure tiles in DIII-D. Deuterium retention of different materials was measured using the {sup 3}He(d,p) {sup 4}He nuclear reaction. For carbon, these measurements showed peak deuterium areal density of about 8 {times} 10 {sup 18} D/cm{sup 2} in a co-deposited layer about 6 {micro}m deep, mainly at the usually detached inboard divertor leg. That layer of carbon near the inner divertor strike point has an atomic saturation concentration of D/C {approx} 0.25, which is not significantly lower than the laboratory-measured saturation retention of 0.4. Under the carbon contaminated background plasma of DIII-D, metal coatings of Be, V, Mo, and W were exposed to the steady state outer strike point under ELMing and ELM-free H-mode discharges. The rate of material erosion and tritium retention were measured. As expected, W shows the lowest erosion rate at 0.1 nm/s and the lowest deuterium uptake.

  8. 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.

  9. Migration of Di- and Tri-Interstitials in Silicon

    SciTech Connect

    Posselt, Matthias; Gao, Fei; Zwicker, D

    2005-01-01

    A comprehensive study on the migration of di- and tri-interstitials in silicon is performed using classical molecular dynamics simulations with the Stillinger-Weber potential. The initial di- and tri-interstitial configurations with the lowest formation energies are determined, and then, the defect migration is investigated for temperatures between 800 and 1600 K. The defect diffusivity and the self-diffusion coefficient per defect are calculated. Compared to the mono-interstitial, the di-interstitial migrates faster, whereas the tri-interstitial diffuses slower. The migration mechanism of the di-interstitial shows a pronounced dependence on the temperature. Like in the case of the mono-interstitial, the mobility of the di-interstitial is higher than the mobility of the lattice atoms during the defect diffusion. On the other hand, the tri-interstitial mobility is lower than the corresponding atomic mobility. The results are compared with data from the literature and the implications of the present results for the analysis of experimental data on defect evolution and migration are discussed.

  10. 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.

  11. Bis(2,3-di­chloro­phen­yl) di­sulfide

    PubMed Central

    Osorio-Yáñez, Rebeca Nayely; Crisóstomo-Lucas, Carmela; Santacruz-Juárez, Ericka; Reyes-Martínez, Reyna; Morales-Morales, David

    2014-01-01

    The title compound, C12H6Cl4S2, features an S—S bond [2.0252 (8) Å] that bridges two 2,3-di­chloro­phenyl rings with a C—S—S—C torsion angle of 88.35 (11)°. The benzene rings are normal one to the other with a dihedral angle of 89.83 (11)°. The crystal structure features inter­molecular Cl⋯Cl [3.4763 (11) Å] and π–π stacking inter­actions [centroid–centroid distances = 3.696 (1) and 3.641 (2) Å]. Intra­molecular C—H⋯S inter­actions are also observed. PMID:24860342

  12. Tetrakis(2,6-di-methyl-pyridinium) di-hydrogen deca-vanadate dihydrate.

    PubMed

    Rakovský, Erik; Krivosudský, Lukáš

    2014-06-01

    The structure of the title compound, (C7H10N)4[H2V10O28]·2H2O, was solved from a non-merohedrally twinned crystal (ratio of twin components ∼0.6:0.4). The asymmetric unit consists of one-half deca-vanadate anion (the other half completed by inversion symmetry), two 2,6-di-methyl-pyridinium cations and one water mol-ecule of crystallization. In the crystal, the components are connected by strong N-H⋯O and O-H⋯O hydrogen bonds, forming a supra-molecular chain along the b-axis direction. There are weak C-H⋯O inter-actions between the chains.

  13. 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.

  14. Quantification of the asymmetric migration of the lipophilic dyes, DiO and DiD, in homotypic co-cultures of chondrosarcoma SW-1353 cells

    PubMed Central

    Lehmann, Tomasz P.; Juzwa, Wojciech; Filipiak, Krystyna; Sujka-Kordowska, Patrycja; Zabel, Maciej; Głowacki, Jakub; Głowacki, Maciej; Jagodziński, Paweł P.

    2016-01-01

    DiO and DiD are lipophilic cell labelling dyes used in the staining of cells in vivo and in vitro. The aim of the present study was to quantify the asymmetrical distribution of dyes in co-cultured cells and to measure the intercellular transfer of DiO and DiD. DiO and DiD were applied separately to stain two identical populations of SW-1353 human chondrosarcoma cells that were subsequently co-cultured (homotypic co-culture). The intercellular migration of dyes in the co-cultured cells was measured by flow cytometry and recorded under a fluorescent microscope. DiD and DiO caused no effect on the proliferation of cells, the degradation rate of the two dyes was comparable and crossover effects between dyes were negligible. The results of the present study suggested that asymmetrical intercellular migration of DiD and DiO was responsible for the asymmetrical distribution of these dyes in co-cultured cells. To take advantage of the lipophilic dyes migration in the double-stained co-cultured cells we suggest to apply mixed-dyes controls prior to the flow cytometric analysis. These controls are performed by staining cells with a 1:1 mix of the two dyes and would enable the estimation of the intensity of intercellular contact in co-culture systems. A 1:1 premix of DiO and DiD was applied to estimate cellular effect on intercellular exchange of lipid dyes in co-cultures incubated with cycloheximide and cytochalasin B. The cellular effect contributed 6–7% of intercellular migration of the lipophilic dyes, DiO and DiD. The majority of the observed intercellular transfer of these dyes was due to non-cellular, passive transfer. PMID:27748852

  15. A case of DiGeorge syndrome in Georgia.

    PubMed

    Chikovani, M; Kutubidze, T; Khvedeliani, N; Pagava, K

    2011-04-01

    Patient 6 - year- old boy, with history of recurrent otitis, cleft palate, was admitted to the hospital for fever, abdominal pain; He had high ESR,CRP, low T lymphocytes, VSD. Peritoneal fluid was positive for pseudomona aeroginoza. Diagnosis of DiGeorge syndrome was confirmed by further genetical study. Immune deficiencies should be considered when infections are severe, persistent resistant to standard treatment, or caused by opportunistic organisms. Treatments can often correct many of the critical and immediate problems associated with DiGeorge syndrome such as heart defects, calcium defects, poor immune system functions and cleft palate. People who had poor immune function as children due to small or missing thymus, may have an increased risk of autoimmune disorders, such as a rheumatoid arthritis and Graves disease. Because DiGeorge syndrome can result in so many disorders, a number of specialists should be involved in diagnosing specific conditions, recommending treatments and providing care.

  16. Placental lesions in a case of DiGeorge sequence.

    PubMed

    Fulcheri, E; Gualco, M; Delfino, F; Pantarotto, M F

    2006-01-01

    This work describes some placental alterations found in a partial form of DiGeorge sequence, namely, hypoplasia of a cord artery with internal calcification of an extensive endoluminal thrombosis, and widespread calcification of microthrombi in the arteries of the second and third order villous branches. Hypoplasia of a cord artery is a relatively rare event, and is also associated with malformations of the gastroenteric and cardiovascular system, as sometimes described in the DiGeorge sequence. Interesting placental alterations are reported and their likely physiopathologic basis and pathogenic correlation discussed in order to give a better and more comprehensive picture of the DiGeorge sequence in which the correlated placental alterations are not sufficiently known.

  17. DiGeorge sequence with hypogammaglobulinemia: a case report.

    PubMed

    Chien, Yin-Hsiu; Yang, Yao-Hsu; Chu, Shau-Yin; Hwu, Wuh-Liang; Kuo, Pao-Lin; Chiang, Bor-Luen

    2002-09-01

    The most common immunodeficiency in DiGeorge sequence patients is defects in T-cell production due to insufficient thymic tissue. However, because T-lymphocytes are important in regulating antibody responses, DiGeorge sequence is no longer regarded as a pure deficiency of cellular immunity but also a form of variable-combined immunodeficiency. Here we presented a 4-month-old male infant with characteristic facial dysmorphism, thymus dysplasia, tetralogy of Fallot, and documented deletion of chromosome 22q11.2 who had decrease B-lymphocyte numbers and hypogammaglobulinemia. The mitogen responses of T-lymphocytes function were normal with adequate number of CD4+ lymphocytes. This case report highlights the importance of evaluating not only the cellular but also the humoral immune function in patients with DiGeorge sequence.

  18. Bis(μ-N,N-di-allyl-dithio-carbamato)bis[(N,N-di-allyl-dithio-carbamato)cadmium].

    PubMed

    Onwudiwe, Damian C; Hrubaru, Madalina; Hosten, Eric C; Arderne, Charmaine

    2017-09-01

    The title compound, [Cd2(C7H10NS2)4], is a neutral dinuclear cadmium(II) complex bearing four bis N,N-di-allyl-di-thio-carbamate ligands coordinating to two Cd(II) cations. In each of the monomeric subunits, there are four S atoms of two di-thio-carbamate ligands [Cd-S = 2.5558 (3), 2.8016 (3), 2.6050 (3) and 2.5709 (3) Å] that coordinate to one Cd(II) atom in a bidentate mode. The dimers are located over an inversion centre bridged by two additional bridging Cd-S bonds [2.6021 (3) Å], leading to a substantial distortion of the geometry of the monomeric subunit from the expected square-planar geometry. The five-coordinate environment around each of the Cd(II) ions in the dimer is best described as substanti-ally tetra-gonally distorted square pyramidal. The di-thio-carbamate groups are themselves planar and are also coplanar with the Cd(II) ions. The negative charge on these groups is delocalized by resonance across the S atoms bound to the Cd(II) cation. This delocalization of the π electrons in the di-thio-carbamate groups also extends to the C-N bonds as they reveal significant double bond character [C-N = 1.3213 (16) and 1.3333 (15) Å].

  19. DiGeorge syndrome: part of CATCH 22.

    PubMed Central

    Wilson, D I; Burn, J; Scambler, P; Goodship, J

    1993-01-01

    DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22q11. We report the clinical findings in 44 cases. We propose that DiGeorge syndrome should be seen as the severe end of the clinical spectrum embraced by the acronym CATCH 22 syndrome; Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia resulting from 22q11 deletions. Images PMID:8230162

  20. 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.

  1. 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.

  2. 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.

  3. Synthesis and photochemical properties of 1,3-di-9-anthryl-2-propanol, 1,3-di-9-anthrylacetone, and related propano-linked anthracenes

    SciTech Connect

    Becker, H.D.; Amin, K.A. )

    1989-06-23

    9-anthryllithium reacts with epichlorohydrin to give 1,3-di-9-anthryl-2-propanol via 3-(9-anthryl)-1-chloro-2-hydroxypropane and 3-(9-anthryl)-1,2-epoxypropane. Oxidation of dianthryl-2-propanol with Dess-Martin reagent gave 1,3-di-9-anthrylacetone. Various other 1,3-bichromophoric anthracenes were synthesized by way of C-methylation of dianthrylacetone, 1,3-di-9-anthryl-1-propanone, and 1,3-di-9-anthrylpropenone. 9-Anthrylacetone, formed as byproduct in the reaction of anthryllithium with epichlorohydrin, was prepared from 9-anthrylacetaldehyde by Grignard reaction with methylmagnesium iodide and subsequent oxidation. The excited-state properties of dianthryl-2-propanol, dianthrylacetone, 1,3-di-9-anthryl-2-methyl-1-propanone, 1,3-di-9-anthryl-2-methyl-2-propanol, diastereomeric 1,3-di-9-anthryl-1-butanols, 1,3-di-9-anthryl-2-butanone, 1,3-di-9-anthryl-1-butanone, and diastereomeric 1,3-di-9-anthryl-2-methyl-1-butanones have been evaluated by fluorescence quantum yields, and by quantum yields for the isomerization by intramolecular 4{pi} + 4{pi} cycloaddition. Dianthryl-2-propanol, 1,3-di-9-antrhyl-2-methyl-2-propanol, dianthrylacetone, diastereomeric 1,3-di-9-anthryl-1-butanols, and 1,3-di-9-anthryl-2-butanone isomerize in their excited singlet state with quantum yields of 0.046, 0.021, 0.25, 0.23, and 0.22, respectively. The photochemical isomerization of those 1,3-bichromophoric anthrancenes which are characterized by a 9-anthroyl chromophore involves the excited triplet state, and the cyclization quantum yield may be as high as 0.72.

  4. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome.

    PubMed

    Patel, Kiran; Akhter, Javeed; Kobrynski, Lisa; Benjamin Gathmann, M A; Gathman, Benjamin; Davis, Onika; Sullivan, Kathleen E

    2012-11-01

    DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge syndrome is associated with significant humoral immune deficiency.

  5. 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 under...

  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 under...

  7. 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 under...

  8. 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 under...

  9. Molecular organization in perylene tetracarboxylic di-imide solid films

    NASA Astrophysics Data System (ADS)

    Akers, K.; Aroca, R.; Hort, A. M.; Loutfy, R. O.

    The vibrational spectra of thin solid films of three perylene tetracarboxylic di-imide derivatives (phenyl, methyl, and unsubstituted) are reported. A preferred molecular orientation in the evaporated solid films emerged for all three perylene derivatives from the i.r. data. Raman spectra obtained in resonance with the absorption band were characteristic of scattering via a Herzberg—Teller mechanism.

  10. URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS

    EPA Science Inventory

    Di-n-octyl phthalate (DnOP) is a plasticizer used in polyvinyl chloride plastics, cellulose esters, and polystyrene resins. The metabolism of DnOP results in the hydrolysis of one ester linkage to produce mono-n-octyl phthalate (MnOP), which subsequently metabolizes to form oxida...

  11. PLCs, DI, & RTI: A Tapestry for School Change

    ERIC Educational Resources Information Center

    Stoehr, Judy; Banks, Maria; Allen, Linda

    2011-01-01

    Rather than buying individual books about professional learning communities (PLCs), differentiated instruction (DI), and Response to Intervention (RTI), invest wisely in one resource that synthesizes all three. The text uses a tapestry analogy to weave together these critical topics to form a comprehensive framework for achieving continuous school…

  12. 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...

  13. 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...

  14. URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS

    EPA Science Inventory

    Di-n-octyl phthalate (DnOP) is a plasticizer used in polyvinyl chloride plastics, cellulose esters, and polystyrene resins. The metabolism of DnOP results in the hydrolysis of one ester linkage to produce mono-n-octyl phthalate (MnOP), which subsequently metabolizes to form oxida...

  15. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Tetraethylene glycol di-(2-ethylhexoate). 178.3940 Section 178.3940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and...

  16. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Tetraethylene glycol di-(2-ethylhexoate). 178.3940 Section 178.3940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  17. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Tetraethylene glycol di-(2-ethylhexoate). 178.3940 Section 178.3940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  18. 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...

  19. 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...

  20. 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.

  1. Di-hadron fragmentation and mapping of the nucleon structure

    NASA Astrophysics Data System (ADS)

    Pisano, Silvia; Radici, Marco

    2016-06-01

    The fragmentation of a colored parton directly into a pair of colorless hadrons is a non-perturbative mechanism that offers important insights into the nucleon structure. Di-hadron fragmentation functions can be extracted from semi-inclusive electron-positron annihilation data. They also appear in observables describing the semi-inclusive production of two hadrons in deep-inelastic scattering of leptons off nucleons or in hadron-hadron collisions. When a target nucleon is transversely polarized, a specific chiral-odd di-hadron fragmentation function can be used as the analyzer of the net density of transversely polarized quarks in a transversely polarized nucleon, the so-called transversity distribution. The latter can be extracted through suitable single-spin asymmetries in the framework of collinear factorization, thus in a much simpler framework with respect to the traditional one in single-hadron fragmentation. At subleading twist, the same chiral-odd di-hadron fragmentation function provides the cleanest access to the poorly known twist-3 parton distribution e( x) , which is intimately related to the mechanism of dynamical chiral symmetry breaking in QCD. When sensitive to details of transverse-momentum dynamics of partons, the di-hadron fragmentation functions for a longitudinally polarized quark can be connected to the longitudinal jet handedness to explore possible effects due to CP -violation of the QCD vacuum. In this review, we outline the formalism of di-hadron fragmentation functions, we discuss different observables where they appear and we present measurements and future worldwide plans.

  2. Clinical Phenotype of DiGeorge Syndrome with Negative Genetic Tests: A Case of DiGeorge-Like Syndrome?

    PubMed

    Laccetta, Gianluigi; Toschi, Benedetta; Fogli, Antonella; Bertini, Veronica; Valetto, Angelo; Consolini, Rita

    2015-01-01

    We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests.

  3. Clinical Phenotype of DiGeorge Syndrome with Negative Genetic Tests: A Case of DiGeorge-Like Syndrome?

    PubMed Central

    Laccetta, Gianluigi; Toschi, Benedetta; Fogli, Antonella; Bertini, Veronica; Valetto, Angelo; Consolini, Rita

    2015-01-01

    We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests. PMID:26793401

  4. Photodegradation of polymer-dispersed perylene di-imide dyes

    NASA Astrophysics Data System (ADS)

    Tanaka, Nobuaki; Barashkov, Nikolay; Heath, Jerry; Sisk, Wade N.

    2006-06-01

    Polymer-dispersed perylene di-imide dye photodegradation is investigated by monitoring the fluorescence intensity as a function of 532 nm laser pulses. Anaerobically irradiated polymer-dye films exhibited an accelerated decrease in fluorescence intensity, which was partially recovered upon exposure to oxygen. Decelerated photodegradation rates were observed for perylene di-imide ethanol solutions upon the addition of a singlet oxygen quenching antioxidant. These observations suggest reversible photoreduction and type II photo-oxidation as important photodegradation mechanisms. Type II photo-oxidation for perylene red 532 nm irradiation is supported by a singlet oxygen quantum yield of 0.09±0.03, determined via detection of time-resolved O2 (a1Δg —> X3∑g-) infrared phosphorescence.

  5. Photodegradation of polymer-dispersed perylene di-imide dyes.

    PubMed

    Tanaka, Nobuaki; Barashkov, Nikolay; Heath, Jerry; Sisk, Wade N

    2006-06-01

    Polymer-dispersed perylene di-imide dye photodegradation is investigated by monitoring the fluorescence intensity as a function of 532 nm laser pulses. Anaerobically irradiated polymer-dye films exhibited an accelerated decrease in fluorescence intensity, which was partially recovered upon exposure to oxygen. Decelerated photodegradation rates were observed for perylene di-imide ethanol solutions upon the addition of a singlet oxygen quenching antioxidant. These observations suggest reversible photoreduction and type II photo-oxidation as important photodegradation mechanisms. Type II photo-oxidation for perylene red 532 nm irradiation is supported by a singlet oxygen quantum yield of 0.09+/-0.03, determined via detection of time-resolved O2 (a1delta(g) --> X3sigma(g)-) infrared phosphorescence.

  6. Thymus transplantation in complete DiGeorge anomaly.

    PubMed

    Markert, M Louise; Devlin, Blythe H; Chinn, Ivan K; McCarthy, Elizabeth A

    2009-01-01

    Complete DiGeorge anomaly is characterized by athymia, congenital heart disease, and hypoparathyroidism. This congenital disease is fatal by age 2 years unless immune reconstitution is successful. There are multiple underlying syndromes associated with complete DiGeorge anomaly including 22q11 hemizygosity in approximately 50%, CHARGE association in approximately 25%, and diabetic embryopathy in approximately 15%. Approximately one-third of patients present with rash and lymphadenopathy associated with oligoclonal "host" T cells. This condition resembles Omenn syndrome. Immunosuppression is necessary to control the oligoclonal T cells. The results of thymus transplantation are reported for a series of 50 patients, of whom 36 survive. The survivors develop naïve T cells and a diverse T cell repertoire.

  7. Dental aspects in patients with DiGeorge syndrome.

    PubMed

    Toka, Okan; Karl, Matthias; Dittrich, Sven; Holst, Stefan; Holst, Alexandra

    2010-01-01

    DiGeorge syndrome, which is caused by a microdeletion of 1.5 to 3.0 megabases on the long arm of chromosome 22, has an incidence of approximately 1:4,000 to 1:5,000 live births. The phenotypic spectrum of this disorder includes congenital heart defects, immunodeficiency due to thymic hypoplasia or aplasia, transient or permanent hypocalcemia due to parathyroid hypoplasia or aplasia, developmental retardation, and psychiatric disorders. Dental aspects in these patients include skeletal malformations, velopharyngeal insufficiency with or without cleft palate, small mouth, and hypotonus orofacial musculature, as well as impaired salivary flow. Enamel aberrations related to hypocalcemia may result in a higher frequency of dental caries. Based on a series of five patients, the medical and dental aspects that have to be considered in the care of patients with DiGeorge syndrome are presented.

  8. Braccio di Ferro: a new haptic workstation for neuromotor rehabilitation.

    PubMed

    Casadio, Maura; Sanguineti, Vittorio; Morasso, Pietro G; Arrichiello, Vincenzo

    2006-01-01

    This technical note describes a new robotic workstation for neurological rehabilitation, shortly named Braccio di Ferro. It has been designed by having in mind the range of forces and the frequency bandwidth that characterize the interaction between a patient and a physical therapist, as well as a number of requirements that we think are essential for allowing a natural haptic interaction: back-driveability, very low friction and inertia, mechanical robustness, the possibility to operate in different planes, and an open software environment, which allows the operator to add new functionalities and design personalized rehabilitation protocols. Braccio di Ferro is an open system and, in the spirit of open source design, is intended to foster the dissemination of robot therapy. Moreover, its combination of features is not present in commercially available systems.

  9. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM ...

    EPA Pesticide Factsheets

    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. Raw data file from our published studies on DIBP specifically requested (6/14/2016) by NCEA scientists for analysis and inclusion in their assessment of this chemical.

  10. Dilated cardiomyopathy: a preventable presentation of DiGeorge Syndrome.

    PubMed

    Jamieson, A; Smith, C J

    2015-01-01

    Patients with cardiac failure require careful evaluation to determine the precise nature of the cause of their illness. Genetic causes of dilated cardiomyopathy are well known but inherited conditions may lead to unexpected consequences through intermediate mechanisms not readily recognised as a feature of the inherited disorder. We describe a case of dilated cardiomyopathy resulting from prolonged hypocalcaemia due to previously undiagnosed hypoparathyroidism resulting from DiGeorge Syndrome and describe the features of this case and the treatment of hypoparathyroidism.

  11. [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.

  12. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM ...

    EPA Pesticide Factsheets

    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. Raw data file from our published studies on DIBP specifically requested (6/14/2016) by NCEA scientists for analysis and inclusion in their assessment of this chemical.

  13. DiGeorge syndrome who developed lymphoproliferative mediastinal mass.

    PubMed

    Kim, Kyu Yeun; Hur, Ji Ae; Kim, Ki Hwan; Cha, Yoon Jin; Lee, Mi Jung; Kim, Dong Soo

    2015-03-01

    DiGeorge syndrome is an immunodeficient disease associated with abnormal development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are the classic triad of DiGeorge syndrome. As this syndrome is characterized by hypoplastic or aplastic thymus, there are missing thymic shadow on their plain chest x-ray. Immunodeficient patients are traditionally known to be at an increased risk for malignancy, especially lymphoma. We experienced a 7-year-old DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray. She visited Severance Children's Hospital hospital with recurrent pneumonia, and throughout her repeated chest x-ray, there was a mass like shadow on anterior mediastinal area. We did full evaluation including chest computed tomography, chest ultrasonography, and chest magnetic resonance imaging. To rule out malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the mass which was thought to be malignancy, was lymphoproliferative lesion.

  14. 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.

  15. 4-Bromo-N-(di-n-propyl-carbamothioyl)-benzamide.

    PubMed

    Binzet, Gün; Flörke, Ulrich; Külcü, Nevzat; Arslan, Hakan

    2009-02-04

    The synthesis of the title compound, C(14)H(19)BrN(2)OS, involves the reaction of 4-bromo-benzoyl chloride with potassium thio-cyanate in acetone followed by condensation of the resulting 4-bromo-benzoyl isothio-cyanate with di-n-propyl-amine. Typical thio-urea carbonyl and thio-carbonyl double bonds, as well as shortened C-N bonds, are observed in the title compound. The short C-N bond lengths in the centre of the mol-ecule reveal the effects of resonance in this part of the mol-ecule. The asymmetric unit of the title compound contains two crystallographically independent mol-ecules, A and B. There is very little difference between the bond lengths and angles of these mol-ecules. In mol-ecule B, one di-n-propyl group is twisted in a -anti-periplanar conformation with C-C-C-H = -179.1 (3)° and the other adopts a -synclinal conformation with C-C-C-H = -56.7 (4)°; in mol-ecule A the two di-n-propyl groups are twisted in + and -anti-periplanar conformations, with C-C-C-H = -179.9 (3) and 178.2 (3)°, respectively. In the crystal, the mol-ecules are linked into dimeric pairs via pairs of N-H⋯S hydrogen bonds.

  16. 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.

  17. 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.

  18. VS2DI: Model use, calibration, and validation

    USGS Publications Warehouse

    Healy, Richard W.; Essaid, Hedeff I.

    2012-01-01

    VS2DI is a software package for simulating water, solute, and heat transport through soils or other porous media under conditions of variable saturation. The package contains a graphical preprocessor for constructing simulations, a postprocessor for displaying simulation results, and numerical models that solve for flow and solute transport (VS2DT) and flow and heat transport (VS2DH). Flow is described by the Richards equation, and solute and heat transport are described by advection-dispersion equations; the finite-difference method is used to solve these equations. Problems can be simulated in one, two, or three (assuming radial symmetry) dimensions. This article provides an overview of calibration techniques that have been used with VS2DI; included is a detailed description of calibration procedures used in simulating the interaction between groundwater and a stream fed by drainage from agricultural fields in central Indiana. Brief descriptions of VS2DI and the various types of problems that have been addressed with the software package are also presented.

  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. 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...

  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. 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...

  4. 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...

  5. 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...

  6. Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae

    PubMed Central

    Koestler, Benjamin J.

    2014-01-01

    Vibrio cholerae is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host. V. cholerae employs the second messenger molecule 3′,5′-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in V. cholerae, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in V. cholerae. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that V. cholerae senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP. PMID:24799624

  7. [L'ortoressia nervosa in un campione di popolazione universitaria italiana].

    PubMed

    Dell'Osso, Liliana; Abelli, Marianna; Carpita, Barbara; Massimetti, Gabriele; Pini, Stefano; Rivetti, Luigi; Gorrasi, Federica; Tognetti, Rosalba; Ricca, Valdo; Carmassi, Claudia

    2016-01-01

    RIASSUNTO. Scopo. Valutare la frequenza e le caratteristiche dei comportamenti ortoressici in una vasta popolazione universitaria. Metodi. Un totale di 2826 individui hanno volontariamente completato in forma anonima l'ORTO-15 presente online, questionario autosomministrabile disegnato e validato con lo scopo di valutare la sintomatologia ortoressica. Come già fatto in studi precedenti, un punteggio totale all'ORTO-15 inferiore a 35 è stato utilizzato come soglia ottimale per evidenziare una tendenza per l'ortoressia nervosa. Inoltre, è stata anche usata una scheda specifica per raccogliere le variabili socio-demografiche. Risultati. Sono stati valutati, nel complesso, 2130 studenti e 696 dipendenti universitari appartenenti all'Università di Pisa. I sintomi ortoressici si sono presentati con una frequenza del 32,7%. Le femmine presentavano una percentuale significativamente maggiore di punteggi sopra-soglia all'ORTO-15, un BMI minore, una maggiore presenza di condizione "sottopeso" e di stile di alimentazione vegano/vegetariano rispetto ai maschi. Discussione. L'ortoressia nervosa, definita come una "fissazione per il mangiare sano", non è inclusa formalmente nel DSM-5. L'emergere di questa condizione come un nuovo possibile prodromo di una sindrome psicologica è stato recentemente enfatizzato dal numero sempre crescente di articoli scientifici. Dal nostro campione di popolazione universitaria emerge che l'essere vegetariani o vegani, la condizione sottopeso, l'appartenere al sesso femminile, l'essere studenti e interessati al presente studio sia significativamente predittivo di un'inclinazione verso l'ortoressia. Conclusioni. I nostri dati contribuiscono a definire la nuova concettualizzazione dell'ortoressia nervosa. Saranno necessari sicuramente altri studi per esplorare i confine diagnostici di questa sindrome, il suo decorso, "l'outcome" e le possibili implicazioni cliniche.

  8. Di-μ-bromido-bis-[bromido(di-2-pyridylmethane-diol-κN,N')copper(II)] dihydrate.

    PubMed

    Westcott, Barry L; Kopp-Vaughn, Kristin M; Daniels, Lee M; Zeller, Matthias

    2008-08-06

    The centrosymmetric title complex, [Cu(2)Br(4)(C(11)H(10)N(2)O(2))(2)]·2H(2)O, was one of three complexes isolated by slow evaporation of an acetonitrile reaction mixture of CuBr(2) with di-2-pyridyl ketone (1:1 molar ratio). The title complex contains a 1:1 metal-to-ligand ratio of copper(II) with the hydrated form of the ligand di-2-pyridylmethane-diol. The copper centers are bridged by bromide donors, leading to a Cu-Cu distance of 4.090 (6) Å. The crystals form as non-merohedral twins with two components related by a 180° rotation around the normal to [100]; the selected sample had a twin ratio of 0.63:0.37.

  9. 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

  10. 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.

  11. 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.

  12. Hadfield holds bubble detectors for the RaDI-N Experiment in the Columbus Module

    NASA Image and Video Library

    2013-01-25

    ISS034-E-034506 (25 Jan. 2013) --- Canadian Space Agency astronaut Chris Hadfield, Expedition 34 flight engineer, holds bubble detectors for the RaDI-N experiment in the International Space Station?s Kibo laboratory. RaDI-N measures neutron radiation levels onboard the space station. RaDI-N uses bubble detectors as neutron monitors which have been designed to only detect neutrons and ignore all other radiation.

  13. 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.

  14. DiO-C/sub 3/-(5) and diS-C/sub 3/-(5): interactions with RBC, ghosts and phospholipid vesicles

    SciTech Connect

    Guillet, E.G.; Kimmich, G.A.

    1981-01-01

    The experiments presented below compare the interaction of diO-C/sub 3/-(5) and diS-C/sub 3/-(5) with erythrocytes, erythrocyte ghosts and phospholipid vesicles derived from erythrocyte membranes. The results confirm earlier reports of diS-C/sub 3/-(5) dimerization in the presence of hemoglobin and of dye aggregate formation in erythrocyte suspensions. DiO-C/sub 3/-(5), on the other hand, binds to vesicles and ghosts freed of hemoglobin in a potential-dependent manner but without forming dye aggregates. The two dyes bind to the different preparations in similar proportions, but diS-C/sub 3/-(5) is bound in amounts 3-40 times greater depending in the degree of polarization. The results show that a mechanism other than binding to hemoglobin must occur in order to explain the potential-dependent binding of both dyes to ghosts and vesicles. A primary interaction must exist between the dye molecule and the lipid bilayer in a biologicl membrane, and this would be expected to occur in the presence of hemoglobin or other cytosolic components. DiO-C/sub 3/-(5) is a better dye to use than diS-C/sub 3/-(5) for mechanistic studies, in order to avoid problems associated with formation of complex aggregates of the latter dye, especially in hyperpolarized membrane suspensions.

  15. DiO-C3-(5) and DiS-C3-(5): Interactions with RBC, ghosts and phospholipid vesicles.

    PubMed

    Guillet, E G; Kimmich, G A

    1981-03-15

    The experiments presented below compare the interaction of diO-C3-(5) and diS-C3-(5) with erythrocytes, erythrocyte ghosts and phospholipid vesicles derived from erythrocyte membranes. The results confirm earlier reports of diS-C3-(5) dimerization in the presence of hemoglobin and of dye aggregate formation in erythrocyte suspensions. DiO-C3-(5), on the other hand, binds to vesicles and ghosts freed of hemoglobin in a potential-dependent manner but without forming dye aggregates. The two dyes bind to the different preparations in similar proportions, but diS-C3-(5) is bound in amounts 3-40 times greater depending on the degree of polarization. The results show that mechanism other than binding to hemoglobin must occur in order to explain the potential-dependent binding of both dyes to ghosts and vesicles. A primary interaction must exist between the dye molecule and the lipid bilayer in a biological membrane, and this would be expected to occur in the presence of hemoglobin or other cytosolic components. DiO-C3-(5) is a better dye to use than diS-C3-(5) for mechanistic studies, in order to avoid problems associated with formation of complex aggregates of the latter dye, especially in hyperpolarized membrane suspensions.

  16. 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.

  17. Crystal structure of di-aqua-bis-(2,6-di-methyl-pyrazine-κN (4))bis-(thio-cyanato-κN)cobalt(II) 2,5-di-methyl-pyrazine monosolvate.

    PubMed

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

    2015-12-01

    In the crystal structure of the title compound, [Co(NCS)2(C6H8N2)2(H2O)2]·C6H8N2, the Co(II) cation is coordinated by the N atoms of two terminal thio-cyanate anions, the O atoms of two water mol-ecules and two N atoms of two 2,6-di-methyl-pyrazine ligands. The coordination sphere of the resulting discrete complex is that of a slightly distorted octa-hedron. The asymmetric unit comprises a Co(II) cation and half of a 2,5-di-methyl-pyrazine ligand, both of which are located on centres of inversion, and a water ligand, a 2,6-di--methyl-pyrazine ligand and one thio-cyanate anion in general positions. In the crystal, the discrete complexes are arranged in such a way that cavities are formed in which the 2,5-di-methyl-pyrazine solvent mol-ecules are located. The coordination of the 2,5-di-methyl-pyrazine mol-ecules to the metal is apparently hindered due to the bulky methyl groups in vicinal positions to the N atoms, leading to a preferential coordination of the 2,6-di-methyl-pyrazine ligands. The discrete complexes are linked by O-H⋯N hydrogen bonds between one water H atom and the non-coordinating N atom of the 2,6-di-methyl-pyrazine ligands. The remaining water H atom is hydrogen bonded to one N atom of the 2,5-di-methyl-pyrazine solvent mol-ecule. This arrangement leads to the formation of a two-dimensional network extending parallel to (010).

  18. 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.

  19. Line plotting program using DI-3000/Grafmaker routines

    NASA Technical Reports Server (NTRS)

    Poppen, William A., Jr.; Smith-Taylor, Rudeen

    1986-01-01

    A line plotting program has been developed using the DI-3000 graphics libraries and incorporates Grafmaker subroutines. The program allows multiple lines on a frame and multiple frames per run. Options such as automatic scaling, linear or single-cycle log graphs, and plot text such as titles, legends and axis labels are incorporated in the program. Greek and other fonts can be used in the plot text as well as upper and lower case text. Plot inputs are specified through a control file. The program also allows display of multiple independent data sets on a single graph.

  20. Dynamic optical nonlinearities in di-furfuryl ether solution

    NASA Astrophysics Data System (ADS)

    Mendonça, C. R.; Barbosa Neto, N. M.; Batista, P. S.; de Souza, M. F.; Zilio, S. C.

    2002-08-01

    Dynamic nonlinear refraction and absorption of di-furfuryl ether dissolved in dichloro-methane are investigated with a frequency-doubled Q-switched and mode-locked Nd:YAG laser. The nonlinear absorption presents a strong reverse saturation that seems promising for use in optical limiting devices. Three contributions are observed for the nonlinear refraction: one fast process related to the singlet population, and two slow accumulative contributions arising from the triplet population and thermal lensing. The time evolution of the optical nonlinearities, modeled by means of a five-energy-level diagram, allows the determination of excited state cross-sections as well as the intersystem crossing lifetime.

  1. 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.

  2. Epigenetic Effects of Di(2-ethylhexyl) Phthalate | Science ...

    EPA Pesticide Factsheets

    Epidemiological and laboratory investigations suggest that, in addition to genetic changes, environmental pollutants can affect human health through altering epigenetic mechanisms including DNA methylation, histone modification, and microRNA expression. There is evidence in animals and humans of an association of di(2-ethylhexyl) phthalate (DEHP) exposure and developmental and reproductive toxicity. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic changes occur upon in utero exposures to several phthalates including DEHP. This poster will be presented at the 45th Annual Meeting of the Environmental Mutagenesis and Genomics Society (EMGS).

  3. Epigenetic Effects of Di(2-ethylhexyl) Phthalate | Science ...

    EPA Pesticide Factsheets

    Epidemiological and laboratory investigations suggest that, in addition to genetic changes, environmental pollutants can affect human health through altering epigenetic mechanisms including DNA methylation, histone modification, and microRNA expression. There is evidence in animals and humans of an association of di(2-ethylhexyl) phthalate (DEHP) exposure and developmental and reproductive toxicity. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic changes occur upon in utero exposures to several phthalates including DEHP. This poster will be presented at the 45th Annual Meeting of the Environmental Mutagenesis and Genomics Society (EMGS).

  4. Expanding the scope of sulfur-centered Arbuzov rearrangement in diethyl/di-n-propyl sulfite for the synthesis of mixed-ligand di-n-butyltin alkanesulfonates.

    PubMed

    Shankar, Ravi; Singh, Atul Pratap; Upreti, Shailesh

    2006-11-13

    A one-pot reaction between di-n-butyltin oxide and diethyl/di-n-propyl sulfite in the presence of an equimolar amount of alkyl iodide proceeds via sulfur-centered Arbuzov rearrangement to afford the corresponding di-n-butyltin (alkoxy)alkanesulfonates n-Bu2Sn(OR')OS(O)2R [R = R' = Et (1), n-Pr (2); R = Me, R' = Et (3), n-Pr (4)]. The compounds 1 and 3 react with methylphosphonic acid under mild conditions to give [n-Bu2Sn(OS(O)2R)OP(O)(OH)Me]n [R = Et (5), Me (6), respectively].

  5. Crystal structure of di-aqua-bis-(2,6-di-methyl-pyrazine-κN)bis-(thio-cyanato-κN)cobalt(II) 2,5-di-methyl-pyrazine tris-olvate.

    PubMed

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

    2015-12-01

    In the crystal structure of the title compound, [Co(NCS)2(C6H8N2)2(H2O)2]·3C6H8N2, the Co(II) cation is coordinated by two terminally N-bound thio-cyanate anions, two water mol-ecules and two 2,6-di-methyl-pyrazine ligands, forming a discrete complex with a slightly distorted octa-hedral N4O2 coordination environment. The asymmetric unit contains one Co(II) cation and three halves of 2,5-di-methyl-pyrazine solvate mol-ecules, all entities being completed by inversion symmetry, as well as one thio-cyanate anion, an aqua ligand and a 2,6-di-methyl-pyrazine ligand, all in general positions. In the crystal, discrete complexes are arranged in a way that cavities are formed where the noncoordinating 2,5-di-methyl-pyrazine mol-ecules are located. The coordination of the latter to the metal is prevented due to the bulky methyl groups in vicinal positions to the N atoms, leading to a preferential coordination through the 2,6-di-methyl-pyrazine ligands. The complex mol-ecules are linked by O-H⋯N hydrogen bonds between the water H atoms and the N atoms of 2,5-di-methyl-pyrazine solvent mol-ecules, leading to a layered structure extending parallel to (100).

  6. 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

  7. 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.

  8. 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.

  9. Photodissociation of HI and DI: Polarization of atomic photofragments

    NASA Astrophysics Data System (ADS)

    Brown, Alex

    2005-02-01

    The complete angular momentum distributions and vector correlation coefficients (orientation and alignment) of ground state I(P3/22) and excited state I(P1/22) atoms resulting from the photodissociation of HI have been computed as a function of photolysis energy. The orientation and alignment parameters aQ(K)(p) that describe the coherent and incoherent contributions to the angular momentum distributions from the multiple electronic states accessed by parallel and perpendicular transitions are determined using a time-dependent wave packet treatment of the dissociation dynamics. The dynamics are based on potential energy curves and transition dipole moments that have been reported previously [R. J. LeRoy, G. T. Kraemer, and S. Manzhos, J. Chem. Phys. 117, 9353 (2002)] and used to successfully model the scalar (total cross section and branching fraction) and lowest order vector (anisotropy parameter β) properties of the photodissociation. Predictions of the aQ(K)(p), parameters for the isotopically substituted species DI are reported and contrasted to the analogous HI results. The resulting polarization for the corresponding H/D partners are also determined and demonstrate that both H and D atoms produced can be highly spin polarized. Comparison of these predictions for HI and DI with experimental measurement will provide the most stringent test of the current model for the electronic structure and the interpretation of the dissociation based on noncoupled excited state dynamics.

  10. Photodissociation dynamics of HI and DI at 157 nm

    NASA Astrophysics Data System (ADS)

    Wang, Fengyan; Lu, I.-Chung; Yuan, Kaijun; Cheng, Yuan; Wu, Malcom; Parker, David H.; Yang, Xueming

    2007-11-01

    Photodissociation dynamics of HI and DI have been studied at 157 nm using the H atom Rydberg tagging time-of-flight technique. The photofragment translational energy distribution spectra and angular distributions of H/D atom products have been measured. Both the I( 2P 3/2) and I( 2P 1/2) products come almost exclusively from a perpendicular transition at 157 nm dissociation process, in agreement with the prediction of LeRoy's model [R.J. LeRoy, G.T. Kraemer, S. Manzhos, J. Chem. Phys. 117 (2002) 9353]. However, the branching ratios of I ∗/I measured in the experiment suggests that weak coupling may take place between the potential energy curves, which is noticeably different from the photodissociation of HI in the UV region. The experimental result in this work also suggests that the repulsive state, which has little contribution to the A-band absorption (33 000-53 000 cm -1), plays a greater role in the dissociation of HI and DI at 157 nm.

  11. Photodissociation of HI and DI: polarization of atomic photofragments.

    PubMed

    Brown, Alex

    2005-02-22

    The complete angular momentum distributions and vector correlation coefficients (orientation and alignment) of ground state I((2)P(32)) and excited state I((2)P(12)) atoms resulting from the photodissociation of HI have been computed as a function of photolysis energy. The orientation and alignment parameters a(Q) ((K))(p) that describe the coherent and incoherent contributions to the angular momentum distributions from the multiple electronic states accessed by parallel and perpendicular transitions are determined using a time-dependent wave packet treatment of the dissociation dynamics. The dynamics are based on potential energy curves and transition dipole moments that have been reported previously [R. J. LeRoy, G. T. Kraemer, and S. Manzhos, J. Chem. Phys. 117, 9353 (2002)] and used to successfully model the scalar (total cross section and branching fraction) and lowest order vector (anisotropy parameter beta) properties of the photodissociation. Predictions of the a(Q) ((K))(p), parameters for the isotopically substituted species DI are reported and contrasted to the analogous HI results. The resulting polarization for the corresponding H/D partners are also determined and demonstrate that both H and D atoms produced can be highly spin polarized. Comparison of these predictions for HI and DI with experimental measurement will provide the most stringent test of the current model for the electronic structure and the interpretation of the dissociation based on noncoupled excited state dynamics.

  12. Di-boson signatures as standard candles for partial compositeness

    NASA Astrophysics Data System (ADS)

    Belyaev, Alexander; Cacciapaglia, Giacomo; Cai, Haiying; Ferretti, Gabriele; Flacke, Thomas; Parolini, Alberto; Serodio, Hugo

    2017-01-01

    Composite Higgs Models are often constructed including fermionic top partners with a mass around the TeV scale, with the top partners playing the role of stabilizing the Higgs potential and enforcing partial compositeness for the top quark. A class of models of this kind can be formulated in terms of fermionic strongly coupled gauge theories. A common feature they all share is the presence of specific additional scalar resonances, namely two neutral singlets and a colored octet, described by a simple effective Lagrangian. We study the phenomenology of these scalars, both in a model independent and model dependent way, including the bounds from all the available searches in the relevant channels with di-boson and di-top final states. We develop a generic framework which can be used to constrain any model containing pseudo-scalar singlets or octets. Using it, we find that such signatures provide strong bounds on the compositeness scale complementary to the traditional EWPT and Higgs couplings deviations. In many cases a relatively light scalar can be on the verge of discovery as a first sign of new physics.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Brucella melitensis cyclic di-GMP phosphodiesterase BpdA controls expression of flagellar genes.

    PubMed

    Petersen, Erik; Chaudhuri, Pallab; Gourley, Chris; Harms, Jerome; Splitter, Gary

    2011-10-01

    Brucella melitensis encounters a variety of conditions and stimuli during its life cycle--including environmental growth, intracellular infection, and extracellular dissemination--which necessitates flexibility of bacterial signaling to promote virulence. Cyclic-di-GMP is a bacterial secondary signaling molecule that plays an important role in adaptation to changing environments and altering virulence in a number of bacteria. To investigate the role of cyclic-di-GMP in B. melitensis, all 11 predicted cyclic-di-GMP-metabolizing proteins were separately deleted and the effect on virulence was determined. Three of these cyclic-di-GMP-metabolizing proteins were found to alter virulence. Deletion of the bpdA and bpdB genes resulted in attenuation of virulence of the bacterium, while deletion of the cgsB gene produced a hypervirulent strain. In a Vibrio reporter system to monitor apparent alteration in levels of cyclic-di-GMP, both BpdA and BpdB displayed a phenotype consistent with cyclic-di-GMP-specific phosphodiesterases, while CgsB displayed a cyclic-di-GMP synthase phenotype. Further analysis found that deletion of bpdA resulted in a dramatic decrease in flagellar promoter activities, and a flagellar mutant showed similar phenotypes to the bpdA and bpdB mutant strains in mouse models of infection. These data indicate a potential role for regulation of flagella in Brucella melitensis via cyclic-di-GMP.

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

    PubMed Central

    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. PMID:24822172

  19. Aspiration pneumonia in the child with DiGeorge syndrome -A case report-.

    PubMed

    Lee, Ji-Young; Han, Yun-Joung

    2011-06-01

    DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests with variable clinical findings. Aspiration pneumonia can be a perioperative complication of great concern in this syndrome. In this report, we present a case of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He developed perioperative aspiration pneumonia but was managed successfully.

  20. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study.

    PubMed

    Selim, Maria Angelica; Markert, Mary L; Burchette, James L; Herman, Christopher M; Turner, John W

    2008-04-01

    DiGeorge syndrome is a congenital anomaly with a constellation of findings that includes thymic hypoplasia. Only a small subset of patients with DiGeorge syndrome has complete athymia, classified as complete DiGeorge anomaly; one third of these patients show an eczematous dermatitis, oligoclonal T-cells and lymphadenopathy, known as atypical complete DiGeorge anomaly. Six biopsies from six patients with the distinctive clinical phenotype of atypical complete DiGeorge anomaly were studied. Every biopsy showed exocytosis (100%), parakeratosis, often confluent and spongiosis (100%). Neutrophilic abscesses (50%), dyskeratosis (67%) and satellite cell necrosis (50%) were seen. Perieccrine and perivascular inflammation were seen in half of the cases. Eosinophils were identified (83%); most commonly in both the epidermis and dermis. All of lymphocytes were CD3 positive. Most (83%) of cases contained T-cell intracellular antigen 1 (TIA-1) positive cells. Special testing of the selected patients using spectratyping identified oligoclonal T-cell populations. The presence of dyskeratotic keratinocytes, satellite cell necrosis and parakeratotic scale with neutrophils characterizes the cutaneous rash seen in this subset of complete DiGeorge syndrome patients. Such skin lesions from patients with DiGeorge anomaly should alert the pathologist to the potential diagnosis of atypical complete DiGeorge anomaly. The pathophysiologic role of the oligoclonal T-cells in this entity requires additional study.

  1. 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...

  2. 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.

  3. Identification of c-di-AMP-Binding Proteins Using Magnetic Beads.

    PubMed

    Kampf, Jan; Gundlach, Jan; Herzberg, Christina; Treffon, Katrin; Stülke, Jörg

    2017-01-01

    To identify cytosolic proteins that bind to cyclic di-AMP, a biotinylated analog of the nucleotide is used for protein pull-down experiments. In this approach, biotinylated c-di-AMP is coupled to Streptactin-covered beads. After protein separation using standard SDS-PAGE, the protein(s) of interest are identified by mass spectrometric analyses.

  4. 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

  5. Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem.

    PubMed

    Nicastro, Gianlucca G; Kaihami, Gilberto H; Pereira, Thays O; Meireles, Diogo A; Groleau, Marie-Christine; Déziel, Eric; Baldini, Regina L

    2014-05-01

    A large number of genes coding for enzymes predicted to synthesize and degrade 3'-5'-cyclic diguanylic acid (c-di-GMP) is found in most bacterial genomes and this dinucleotide emerged as an intracellular signal-controlling bacterial behaviour. An association between high levels of c-di-GMP and antibiotic resistance may be expected because c-di-GMP regulates biofilm formation and this mode of growth leads to enhanced antibiotic resistance. However, a clear understanding of this correlation has not been established. We found that increased levels of c-di-GMP in Pseudomonas aeruginosa improve fitness in the presence of imipenem, even when grown as planktonic cells. P. aeruginosa post-transcriptionally regulates the amounts of five porins in response to c-di-GMP, including OprD, responsible for imipenem uptake. Cells with low c-di-GMP levels are consequently more sensitive to this antibiotic. Main efflux pumps or β-lactamase genes did not show altered mRNA levels in P. aeruginosa strains with modified different c-di-GMP concentrations. Together, our findings show that c-di-GMP levels modulate fitness of planktonic cultures in the presence of imipenem. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Efficient hydrogenation of biomass-derived cyclic di-esters to 1,2-diols.

    PubMed

    Balaraman, Ekambaram; Fogler, Eran; Milstein, David

    2012-01-28

    The unprecedented homogeneous hydrogenation of cyclic di-esters, in particular biomass-derived glycolide and lactide, to the corresponding 1,2-diols is catalyzed by Ru(II) PNN (1) and Ru(II) CNN (2) pincer complexes under mild hydrogen pressure and (in the case of 1) neutral conditions. No racemization was observed when a chiral di-ester was used.

  7. 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...

  8. Growth and antioxidant defense responses of wheat seedlings to di-n-butyl phthalate and di (2-ethylhexyl) phthalate stress.

    PubMed

    Gao, Minling; Dong, Youming; Zhang, Ze; Song, Wenhua; Qi, Yun

    2017-04-01

    Phthalate acid esters (PAEs) are vital environmental hormone-like chemicals that are noxious to plants, animals, and human beings. In this study, the influences of di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) on the seed germination, root morphology, and various physiological changes of wheat seedlings were investigated by analyzing superoxide anion (O2(-)) accumulation, antioxidant enzyme activity, and lipid peroxidation. DBP and DEHP were found to obviously inhibit germination only at high concentrations, but significantly affected root morphology even at lower concentrations. Their toxic effects were the most severe on root elongation, followed by shoot elongation, and were the least severe on germination rate, indicating that root elongation was the best index for evaluating DBP and DEHP eco-toxicity. DBP and DEHP also enhanced O2(-) and malondialdehyde levels and membrane permeability, as well as produced changes in the antioxidant status and PAE content in the stem and leaf (combined tissues, hereafter shoot) and root tissues. The activities of superoxide dismutase, catalase, and peroxidase increased at low and medium DBP and DEHP concentrations, but declined at high PAE concentrations. These results indicated that PAEs could exert oxidative damage in the early development stage of wheat, particularly at higher concentrations. DBP and DEHP accumulation was higher in the roots than in the shoot tissues, and their levels in these tissues increased with increasing PAE concentrations, supporting their more-serious toxic effects on roots than those on shoots. Further, the physicochemical properties of DBP rendered it more harmful than DEHP.

  9. 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.

  10. The ins and outs of cyclic di-GMP signaling in Vibrio cholerae.

    PubMed

    Conner, Jenna G; Zamorano-Sánchez, David; Park, Jin Hwan; Sondermann, Holger; Yildiz, Fitnat H

    2017-04-01

    The second messenger nucleotide cyclic dimeric guanosine monophosphate (c-di-GMP) governs many cellular processes in the facultative human pathogen Vibrio cholerae. This organism copes with changing environmental conditions in aquatic environments and during transitions to and from human hosts. Modulation of c-di-GMP allows V. cholerae to shift between motile and sessile stages of life, thus allowing adaptation to stressors and environmental conditions during its transmission cycle. The V. cholerae genome encodes a large set of proteins predicted to degrade and produce c-di-GMP. A subset of these enzymes has been demonstrated to control cellular processes - particularly motility, biofilm formation, and virulence - through transcriptional, post-transcriptional, and translational mechanisms. Recent studies have identified and characterized enzymes that modulate or sense c-di-GMP levels and have led towards mechanistic understanding of c-di-GMP regulatory circuits in V. cholerae. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Interactions of the c-di-GMP riboswitch with its second messenger ligand

    PubMed Central

    Smith, Kathryn D.; Strobel, Scott A.

    2013-01-01

    The c-di-GMP riboswitch is a macromolecular target in the c-di-GMP second messenger signaling pathway. It regulates many genes related to c-di-GMP metabolism as well as genes involved in bacterial motility, virulence and biofilm formation. The riboswitch makes asymmetric contacts to the bases and phosphate backbone of this symmetric dinucleotide. The phylogenetics suggested and mutagenesis has confirmed that this is a flexible motif where variants can make alternative interactions with each of the guanine bases of c-di-GMP. A mutant riboswitch has been designed that can bind a related molecule, c-di-AMP, confirming the most important contacts made to the ligand. The binding kinetics reveal that this is a kinetically controlled riboswitch and mutations to the riboswitch lead to increases in the off-rate. This riboswitch is therefore flexible in sequence as well as kinetic properties. PMID:21428955

  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. 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 .

  14. 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

  15. Remote Sensing Global Surface Air Pressure Using Differential Absorption BArometric Radar (DiBAR)

    NASA Technical Reports Server (NTRS)

    Lin, Bing; Harrah, Steven; Lawrence, Wes; Hu, Yongxiang; Min, Qilong

    2016-01-01

    Tropical storms and severe weathers are listed as one of core events that need improved observations and predictions in World Meteorological Organization and NASA Decadal Survey (DS) documents and have major impacts on public safety and national security. This effort tries to observe surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at the 50-55 gigahertz O2 absorption band. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 4 millibars (approximately 1 millibar under all weather conditions). With these sea level pressure measurements, the forecasts of severe weathers such as hurricanes will be significantly improved. Since the development of the DiBAR concept about a decade ago, NASA Langley DiBAR research team has made substantial progress in advancing the concept. The feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. The team has developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.

  16. Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.

    PubMed

    Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M

    2013-05-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis.

  17. 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

  18. Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose

    PubMed Central

    Zorraquino, Violeta; García, Begoña; Latasa, Cristina; Echeverz, Maite; Toledo-Arana, Alejandro; Valle, Jaione

    2013-01-01

    Cyclic di-GMP (c-di-GMP) is a secondary messenger that controls a variety of cellular processes, including the switch between a biofilm and a planktonic bacterial lifestyle. This nucleotide binds to cellular effectors in order to exert its regulatory functions. In Salmonella, two proteins, BcsA and YcgR, both of them containing a c-di-GMP binding PilZ domain, are the only known c-di-GMP receptors. BcsA, upon c-di-GMP binding, synthesizes cellulose, the main exopolysaccharide of the biofilm matrix. YcgR is dedicated to c-di-GMP-dependent inhibition of motility through its interaction with flagellar motor proteins. However, previous evidences indicate that in the absence of YcgR, there is still an additional element that mediates motility impairment under high c-di-GMP levels. Here we have uncovered that cellulose per se is the factor that further promotes inhibition of bacterial motility once high c-di-GMP contents drive the activation of a sessile lifestyle. Inactivation of different genes of the bcsABZC operon, mutation of the conserved residues in the RxxxR motif of the BcsA PilZ domain, or degradation of the cellulose produced by BcsA rescued the motility defect of ΔycgR strains in which high c-di-GMP levels were reached through the overexpression of diguanylate cyclases. High c-di-GMP levels provoked cellulose accumulation around cells that impeded flagellar rotation, probably by means of steric hindrance, without affecting flagellum gene expression, exportation, or assembly. Our results highlight the relevance of cellulose in Salmonella lifestyle switching as an architectural element that is both essential for biofilm development and required, in collaboration with YcgR, for complete motility inhibition. PMID:23161026

  19. 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

  20. 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

  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.

  2. Bile acids and bicarbonate inversely regulate intracellular cyclic di-GMP in Vibrio cholerae.

    PubMed

    Koestler, Benjamin J; Waters, Christopher M

    2014-07-01

    Vibrio cholerae is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host. V. cholerae employs the second messenger molecule 3',5'-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in V. cholerae, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in V. cholerae. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that V. cholerae senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. 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

  4. Preimplantation genetic diagnosis of DiGeorge syndrome.

    PubMed

    Iwarsson, E; Ahrlund-Richter, L; Inzunza, J; Fridström, M; Rosenlund, B; Hillensjö, T; Sjöblom, P; Nordenskjöld, M; Blennow, E

    1998-09-01

    We report the first case of preimplantation genetic diagnosis used in order to avoid chromosomal imbalance in the progeny of a woman mildly affected by DiGeorge syndrome and carrier of a microdeletion of chromosome 22q11.2. In total, seven embryos were biopsied in three separate treatments and analysed by fluorescent in-situ hybridization (FISH). Of these, four were carrying the deletion, two were normal and in one the analysis was inconclusive. The diagnostic procedure was performed within 5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred in the third treatment, but no pregnancy was established. Patients with a 22q11 microdeletion, who have a 50% risk of transmitting the deletion to their offspring, can now be offered preimplantation genetic diagnosis using FISH for the detection of a 22q11 deletion.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

    Petreska, Elena

    2016-12-01

    We propose a factorization formula for the cross section for forward di-jet production in dilute-dense collisions. The new formula is applicable for an arbitrary value of the momentum imbalance of the two jets, kt. It unifies the previously derived transverse momentum dependent (TMD) factorization for small kt (of the order of the saturation scale), and the High Energy Factorization (HEF) for large kt (of the order of the momentum of the jets). We extend the previous TMD formula, first to finite Nc, and then to all ranges of kt by including off-shell matrix elements. We present previously unpublished analytical expressions for the TMD gluon distributions in the Golec-Biernat-Wusthoff model, and their perturbative behaviour in the McLerran-Venugopalan model. In addition, we show directly the equivalence of the HEF and the color glass condensate formulae in the dilute target approximation.

  7. Test and Analysis of Spliced DI-BSCCO HTS Tapes

    NASA Astrophysics Data System (ADS)

    Fetisov, S. S.; Sotnikov, D. V.; Radchenko, I. P.; Vysotsky, V. S.; Osabe, G.; Kinoshita, K.; Fujikami, J.; Kobayashi, S.; Yamazaki, K.

    For some applications, short unit lengths of HTS wires should be spliced if longer lengths are necessary and short unit lengths of HTS wires should be utilize by applying the splice technology to reduce the total wire cost in the application. The splice technology has been developed for DI-BSCCO Type HT-CA tapes by Sumitomo Electric and spliced tapes were tested in Russian Cable Institute. The test program included: measurements of splice's resistance, critical current anisotropy, thermo cycling tolerance, mechanical properties, overload tests and magnetization measurements. In the paper the results of tests are presented and discussed. The test results demonstrated that splices can be used for cable production if twisting and bending limitations are taken into account.

  8. Study of viscosity of mono-, di-, and trialkylamines

    NASA Astrophysics Data System (ADS)

    Oswal, S. L.; Sindhe, R. G.; Patel, A. T.; Dave, J. P.; Patel, S. G.; Patel, B. M.

    1992-07-01

    Viscosities of several mono-, di-, and trialkylamines have been measured in the temperature range 298 to 333 K. It is observed that viscosities are highly dependent on shape, size, and association through H-bond or through dipole. Following the transition state theory, energy, Gibbs free energy, and entropy of activation of viscous flow have been calculated. The values of expansion energy for these liquids have also been calculated using free volume theory, and subsequently amines have been classified as volume-restrained or energy-restrained liquids. The group contribution method of Van Velzen, Cardozo, and Langenkamp for estimating viscosity has been examined with the present and literature data, and the new group contribution increments ΔN i and ΔB i for amines have been evaluated.

  9. Research methodology in the "Associazione Italiana di Radioterapia Oncologica (AIRO)".

    PubMed

    Emiliani, E

    2000-01-01

    The research methodology in the "Associazione Italiana di Radioterapia (AIRO)" (The Italian Association of Radiation Oncology) is presented according to two interconnected aspects: the consensus research on similar projects with other Scientific Associations and the clinical research carried out in the ten years of life of the Association. The mechanism of the "Federazione Intersocietaria" (Federation of Associations) with the Radiology, Oncology and Physics Associations can be a stimulant to broaden the horizons and feasibility of cancer research which is one of the main causes of mortality and which is increasing due to the population aging. The results of three national multicentric trials on the clinical research on cancer of the rectum, oropharynx and in the elderly, are reported. The study methodology, based on the clinical evidence and multidisciplinarity, shows that the time is ripe for a development of research and, if coordinated by the Association, it would contribute to the prestige and importance of the Italian Radiotherapy.

  10. Metabolic studies with di(aziridin-i-yl) sulphoxide (diethyleneiminosulphoxide)

    PubMed Central

    Craig, A. W.; Jackson, H.; James, R. M. V.

    1963-01-01

    The work described was undertaken after the observation that the diuresis induced by several derivatives of ethyleneimine could be correlated with their content of ethyleneimine. The preparation of 35S-labelled di(aziridin-1-yl) sulphoxide (diethyleneiminosulphoxide) is described together with its metabolism in rat, mouse, rabbit and dog. The drug was completely metabolized in all species and, with the exception of the dog, most of the activity was excreted in the urine within 3 days. The main radioactive metabolite in all species was sulphate. In vitro studies demonstrated that the compound was slowly broken down to sulphite and free ethyleneimine; this hydrolysis was greatly accelerated in the presence of phosphate. PMID:14110758

  11. Molecular dynamics simulations of DiI-C18(3) in a DPPC lipid bilayer

    PubMed Central

    Gullapalli, Ramachandra R.

    2011-01-01

    We performed a 40 ns simulation of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI-C18(3)) in a 1,2-dipalmitoyl-sn-glycero-3-phosphatidyl choline (DPPC) bilayer in order to facilitate interpretation of lipid dynamics and membrane structure from fluorescence lifetime, anisotropy, and fluorescence correlations spectroscopy (FCS). Incorporation of DiI of 1.6 to 3.2 mol% induced negligible changes in area per lipid but detectable increases in bilayer thickness, each of which are indicators of membrane structural perturbation. The DiI chromophore angle was 77 ± 17° with respect to the bilayer normal, consistent with rotational diffusion inferred from polarization studies. The DiI headgroup was located 0.63 nm below the lipid head group–water interface, a novel result in contrast to some popular cartoon representations of DiI but consistent with DiI’s increase in quantum yield when incorporated into lipid bilayers. Importantly, the fast component of rotational anisotropy matched published experimental results demonstrating that sufficient free volume exists at the sub-interfacial region to support fast rotations. Simulations with non-charged DiI head groups exhibited DiI flip-flop, demonstrating that the positively-charged chromophore stabilizes the orientation and location of DiI in a single monolayer. DiI induced detectable changes in interfacial properties of water ordering, electrostatic potential, and changes in P–N vector orientation of DPPC lipids. The diffusion coefficient of DiI (9.7 ± 0.02 × 10−8 cm2 s−1) was similar to the diffusion of DPPC molecules (10.7 ± 0.04 × 10−8 cm2 s−1), supporting the conclusion that DiI dynamics reflect lipid dynamics. These results provide the first atomistic level insight into DiI dynamics, results essential in elucidating lipid dynamics through single molecule fluorescence studies. PMID:18548161

  12. Optogenetic Module for Dichromatic Control of c-di-GMP Signaling.

    PubMed

    Ryu, Min-Hyung; Fomicheva, Anastasia; Moskvin, Oleg V; Gomelsky, Mark

    2017-09-15

    Many aspects of bacterial physiology and behavior, including motility, surface attachment, and the cell cycle, are controlled by cyclic di-GMP (c-di-GMP)-dependent signaling pathways on the scale of seconds to minutes. Interrogation of such processes in real time requires tools for introducing rapid and reversible changes in intracellular c-di-GMP levels. Inducing the expression of genes encoding c-di-GMP-synthetic (diguanylate cyclases) and -degrading (c-di-GMP phosphodiesterase) enzymes by chemicals may not provide adequate temporal control. In contrast, light-controlled diguanylate cyclases and phosphodiesterases can be quickly activated and inactivated. A red/near-infrared-light-regulated diguanylate cyclase, BphS, was engineered previously, yet a complementary light-activated c-di-GMP phosphodiesterase has been lacking. In search of such a phosphodiesterase, we investigated two homologous proteins from Allochromatium vinosum and Magnetococcus marinus, designated BldP, which contain C-terminal EAL-BLUF modules, where EAL is a c-di-GMP phosphodiesterase domain and BLUF is a blue light sensory domain. Characterization of the BldP proteins in Escherichia coli and in vitro showed that they possess light-activated c-di-GMP phosphodiesterase activities. Interestingly, light activation in both enzymes was dependent on oxygen levels. The truncated EAL-BLUF fragment from A. vinosum BldP lacked phosphodiesterase activity, whereas a similar fragment from M. marinus BldP, designated EB1, possessed such activity that was highly (>30-fold) upregulated by light. Following light withdrawal, EB1 reverted to the inactive ground state with a half-life of ∼6 min. Therefore, the blue-light-activated phosphodiesterase EB1 can be used in combination with the red/near-infrared-light-regulated diguanylate cyclase BphS for the bidirectional regulation of c-di-GMP-dependent processes in E. coli as well as other bacterial and nonbacterial cells.IMPORTANCE Regulation of motility

  13. Three-dimensional integration (3DI) of semiconductor circuit layers: New devices and fabrication process

    NASA Astrophysics Data System (ADS)

    Sehari, Babak E.

    1998-12-01

    The device density of Integrated Circuits (ICs) manufactured by current VLSI technology is reaching its theoretical limit. Nevertheless, the demand for integration of more devices per chip is growing. To accommodate this need three main possibilities can be explored: Wafer Scale Integration (WSI), Ultra Large Scale Integration (ULSI), and Three Dimensional Integration (3DI). A brief review of these techniques along with their comparative advantages and disadvantages is presented. It has been concluded that 3DI technology is superior to others. Therefore, an attempt is made to develop a viable fabrication process for this technology. This is done by first reviewing the current technologies that are utilized for fabrication of Integrated Circuits (ICs) and their compatibility with 3DI stringent requirements. Based on this review, a set of fabrication procedure for realization of 3DI technology, are presented in chapter 3. In Chapter 1 the compatibility of the currently used devices, such as BJTs and FETs, with 3DI technology is examined. Moreover, a new active device is developed for 3DI technology to replace BJTs and FETs in circuits. This new device is more compatible to the constrains of 3DI technology. Chapter 2 is devoted to solving the overall problems of 3DI circuits. The problem of heat and power dispassion and signal coupling (Cross-Talk) between the layers are reviewed, and an inter-layer shield is proposed to overcome these problems. The effectiveness of such a thin shield is considered theoretically. In Chapter 3 a fabrication process for 3DI technology is proposed. This is done after a short analysis of previous attempts in developing 3DI technologies. Chapter 4 focuses on analog extension of 3DI technology. Moreover, in this chapter microwave 3DI circuits or 3DI MMIC is investigated. Practical considerations in choice of material for the proposed device is the subject of study in Chapter 5. Low temperature ohmic contact and utilization of metal

  14. A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer immunotherapy.

    PubMed

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

    2014-06-28

    Cyclic dinucleotides are of importance in the field of microbiology and immunology. They function as second messengers and are thought to participate in the signal transduction of cytosolic DNA immune responses. One such dinucleotide, cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons. Therefore c-di-GMP can be thought of as a new class of adjuvant. However, because c-di-GMP contains two phosphate groups, this prevents its use as an adjuvant because it cannot pass through the cell membrane, even though the target molecule of c-di-GMP is located in the cytoplasm. Our group has been developing a series of liposomal drug delivery systems and recently investigated YSK05 which is a synthetic, pH sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN-β in Raw264.7 cells. The induction of IFN-β from c-di-GMP liposomes was inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of IFN-β caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I. The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell activity and the inhibition of tumor growth in a mouse model. These findings indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di-GMP to the cytosol and induce an innate immune system but also as a platform for investigating the mechanism of immune sensing with cyclic dinucleotides in vitro and in vivo.

  15. 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

  16. Theoretical study of the effects of di-muonic molecules on muon-catalyzed fusion

    NASA Astrophysics Data System (ADS)

    Sheely, Eugene V.

    This document presents a theoretical study di-muonic hydrogen and helium molecules that have the potential of enhancing the muon-catalyzed fusion reaction rate. In order to study these di-muonic molecules a method of non-adiabatic quantum mechanics referred to as a General Particle Orbital (GPO) method was developed. Three mechanisms that have the possibility of enhancing the muon-catalyzed fusion rate were discovered. Two involve the formation of di-muonic hydrogen molecules, and the other uses di-muonic molecules to liberate muons stuck to 3He nuclei. The effects of muon spin on di-muonic hydrogen molecules was studied. The nuclear separation in di-muonic hydrogen molecules with parallel muon spin is too great for the molecules to have a fusion rate which can enhance the fusion yield. The possibility of these molecules transitioning to single muon molecules or triatomic oblate symmetric top molecules which may fuse faster is examined. Using two muons to catalyze 3He-3He fusion is shown to be impractical; however, using two muons to catalyze 3He-d fusion is possible. While studying the physical properties of di-muonic hydrogen and helium molecules some unique properties were discovered. Correlation interactions in these molecules result in an increase in the calculated nuclear bond length.

  17. The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

    PubMed Central

    Libanova, Rimma; Lienenklaus, Stefan; Weiss, Siegfried; Guzmán, Carlos A.

    2014-01-01

    The cyclic di-nucleotide bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) is a candidate mucosal adjuvant with proven efficacy in preclinical models. It was shown to promote specific humoral and cellular immune responses following mucosal administration. To date, there is only fragmentary knowledge on the cellular and molecular mode of action of c-di-AMP. Here, we report on the identification of dendritic cells and macrophages as target cells of c-di-AMP. We show that c-di-AMP induces the cell surface up-regulation of T cell co-stimulatory molecules as well as the production of interferon-β. Those responses were characterized by in vitro experiments with murine and human immune cells and in vivo studies in mice. Analyses of dendritic cell subsets revealed conventional dendritic cells as principal responders to stimulation by c-di-AMP. We discuss the impact of the reported antigen presenting cell activation on the previously observed adjuvant effects of c-di-AMP in mouse immunization studies. PMID:24755640

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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.

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

    PubMed Central

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

    2014-01-01

    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

  20. DiI staining of fine branches of Bonghan ducts on surface of rat abdominal organs.

    PubMed

    Lee, Byung-Cheon; Jhang, Seong-Uk; Choi, Jae-Hong; Lee, So-Yeong; Ryu, Pan-Dong; Soh, Kwang-Sup

    2009-12-01

    Novel thread-like structures and corpuscles, designated Bonghan ducts (BHDs) and corpuscles (BHCs), are known to form a system of networked channels. Here, we tested the effectiveness of a fluorescent carbocyanine dye, DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), in staining BHDs and BHCs. DiI solution was infused into a BHC on the surface of a rat abdominal organ at a steady rate and the resulting labeling of neighboring BHCs connected via BHDs was examined, as identified by the red fluorescence of DiI. BHDs diameters tapered away from BHCs and formed tree-like branches with fine arborizations embedded in the membranous tissues at their terminal parts. In the proximal parts, DiI fluorescence appeared as continuous lines within BHDs, but a large portion of BHDs remained unstained. In the distal parts of BHDs, discontinuous elongated DiI microparticles were identified along the sinuses within BHDs. The results showed that inner spaces within the BHDs allowed DiI to flow and that BHDs have tree-like branches and terminal arborizations. In conclusion, DiI can be used in visualizing BHDs fine structures.

  1. 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

  2. Functional Characterization of Core Components of the Bacillus subtilis Cyclic-Di-GMP Signaling Pathway

    PubMed Central

    Gao, Xiaohui; Mukherjee, Sampriti; Matthews, Paige M.; Hammad, Loubna A.; Kearns, Daniel B.

    2013-01-01

    Bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that regulates adaptation processes, including biofilm formation, motility, and virulence in Gram-negative bacteria. In this study, we have characterized the core components of a c-di-GMP signaling pathway in the model Gram-positive bacterium Bacillus subtilis. Specifically, we have directly identified and characterized three active diguanylate cyclases, DgcP, DgcK, and DgcW (formerly YtrP, YhcK, and YkoW, respectively), one active c-di-GMP phosphodiesterase, PdeH (formerly YuxH), and a cyclic-diguanylate (c-di-GMP) receptor, DgrA (formerly YpfA). Furthermore, elevation of c-di-GMP levels in B. subtilis led to inhibition of swarming motility, whereas biofilm formation was unaffected. Our work establishes paradigms for Gram-positive c-di-GMP signaling, and we have shown that the concise signaling system identified in B. subtilis serves as a powerful heterologous host for the study of c-di-GMP enzymes from bacteria predicted to possess larger, more-complex signaling systems. PMID:23893111

  3. Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation

    PubMed Central

    Gundlach, Jan; Rath, Hermann; Herzberg, Christina; Mäder, Ulrike; Stülke, Jörg

    2016-01-01

    The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR. PMID:27252699

  4. Identification of c-di-GMP derivatives resistant to an EAL domain phosphodiesterase

    PubMed Central

    Shanahan, Carly A.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2013-01-01

    The bacterial second messenger signaling molecule bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) controls important biological processes such as biofilm formation, virulence response, and motility. This second messenger is sensed by macromolecular targets inside the cell, both protein and RNA, which induce specific phenotypic responses critical for bacterial survival. One class of enzymes responsible for regulating the intracellular concentration of c-di-GMP, and therefore the physiological behavior of the cell, is the EAL domain phosphodiesterases, which degrade the second messenger to its linear form, pGpG. Here, we investigate how base and backbone modifications to c-di-GMP affect the rate of cyclic dinucleotide degradation by an EAL domain protein (CC3396 from Caulobacter crescentus). The doubly substituted thiophosphate analog is highly resistant to hydrolysis by this metabolizing enzyme but can still bind c-di-GMP riboswitch targets. We used these findings to develop a novel ribosyl-phosphate modified derivative of c-di-GMP containing 2′-deoxy and methylphosphonate substitutions that is charge neutral and demonstrate that this analog is also resistant to EAL domain catalyzed degradation. This suggests a general strategy for designing c-di-GMP derivatives with increased enzymatic stability that also possess desirable properties for development as chemical probes of c-di-GMP signaling. PMID:23256840

  5. Cyclic di-AMP Released from Staphylococcus aureus Biofilm Induces a Macrophage Type I Interferon Response

    PubMed Central

    Gries, Casey M.; Bruger, Eric L.; Moormeier, Derek E.; Scherr, Tyler D.; Waters, Christopher M.

    2016-01-01

    Staphylococcus aureus is a leading cause of community- and nosocomial-acquired infections, with a propensity for biofilm formation. S. aureus biofilms actively skew the host immune response toward an anti-inflammatory state; however, the biofilm effector molecules and the mechanism(s) of action responsible for this phenomenon remain to be fully defined. The essential bacterial second messenger cyclic diadenylate monophosphate (c-di-AMP) is an emerging pathogen-associated molecular pattern during intracellular bacterial infections, as c-di-AMP secretion into the infected host cytosol induces a robust type I interferon (IFN) response. Type I IFNs have the potential to exacerbate infectious outcomes by promoting anti-inflammatory effects; however, the type I IFN response to S. aureus biofilms is unknown. Additionally, while several intracellular proteins function as c-di-AMP receptors in S. aureus, it has yet to be determined if any extracellular role for c-di-AMP exists and its release during biofilm formation has not yet been demonstrated. This study examined the possibility that c-di-AMP released during S. aureus biofilm growth polarizes macrophages toward an anti-inflammatory phenotype via type I interferon signaling. DacA, the enzyme responsible for c-di-AMP synthesis in S. aureus, was highly expressed during biofilm growth, and 30 to 50% of total c-di-AMP produced from S. aureus biofilm was released extracellularly due to autolytic activity. S. aureus biofilm c-di-AMP release induced macrophage type I IFN expression via a STING-dependent pathway and promoted S. aureus intracellular survival in macrophages. These findings identify c-di-AMP as another mechanism for how S. aureus biofilms promote macrophage anti-inflammatory activity, which likely contributes to biofilm persistence. PMID:27736778

  6. 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.

  7. Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

    PubMed Central

    Chen, Li-Hong; Köseoğlu, Volkan K.; Güvener, Zehra T.; Myers-Morales, Tanya; Reed, Joseph M.; D'Orazio, Sarah E. F.; Miller, Kurt W.; Gomelsky, Mark

    2014-01-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

  8. Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes.

    PubMed

    Chen, Li-Hong; Köseoğlu, Volkan K; Güvener, Zehra T; Myers-Morales, Tanya; Reed, Joseph M; D'Orazio, Sarah E F; Miller, Kurt W; Gomelsky, Mark

    2014-08-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence.

  9. Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway

    PubMed Central

    Russell, Matthew H.; Bible, Amber N.; Fang, Xin; Gooding, Jessica R.; Campagna, Shawn R.; Gomelsky, Mark; Alexandre, Gladys

    2013-01-01

    ABSTRACT Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors. PMID:23512960

  10. 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.

  11. 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.

  12. 1,1'-(Ethane-1,2-di-yl)dipyridinium bis-(1,2-di-cyano-ethene-1,2-di-thiol-ato-κ(2) S,S')cuprate(II).

    PubMed

    Hu, Bing-Xiang; Zhou, Chang-Xiao; Liu, Yang-Mei; Chen, Li-Zhuang; Wang, Fang-Ming

    2013-06-01

    In the title ion-pair complex, (C12H14N2)[Cu(C4N2S2)2], the complex anion exhibits a highly twisted coordination environment around the tetra-coordinated Cu(II) atom. The dihedral angles between the 1,2-di-cyano-ethene-1,2-di-thiol-ato ligands and between the two pyridine rings in the cation are 37.49 (3) and 29.18 (10)°, respectively. Weak C-H⋯N and C-H⋯S hydrogen bonds link the cations and anions into a three-dimensional network.

  13. Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy

    NASA Astrophysics Data System (ADS)

    Yang, Yun; Zhang, Lijuan; Deng, Guo-Jun; Gong, Hang

    2017-01-01

    A practical, efficient, and operationally simple strategy for the ipsoiododecarboxylation and di-iodination of aromatic carboxylic acids using the low-cost commercial reagent succinimide (NIS) as iodine source is reported. This iodination or di-iodination process can be easily controlled through reaction conditions, thereby providing corresponding iodination or di-iodination products with high yields. Furthermore, these two reactions can be easily scaled up to gram-scale by using palladium catalyst (0.66 mol%), which provides high isolated yield.

  14. Interaction of potassium mono and di phosphates with bovine serum albumin studied by fluorescence quenching method.

    PubMed

    Bakkialakshmi, S; Shanthi, B; Chandrakala, D

    2011-03-01

    The interactions between potassium mono and di phosphates and bovine serum albumin (BSA) were studied using fluorescence spectroscopy (FS) and ultraviolet spectroscopy (UV). The experimental results showed that the potassium mono and di phosphates could insert into the BSA and quench the inner fluorescence of BSA by forming the potassium mono phosphate-BSA and pottassium di phosphate-BSA complexes. It was found that the static quenching was the main reason leading to the fluorescence quenching. It was conformed by XRD and SEM techniques.

  15. Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy

    PubMed Central

    Yang, Yun; Zhang, Lijuan; Deng, Guo-Jun; Gong, Hang

    2017-01-01

    A practical, efficient, and operationally simple strategy for the ipsoiododecarboxylation and di-iodination of aromatic carboxylic acids using the low-cost commercial reagent succinimide (NIS) as iodine source is reported. This iodination or di-iodination process can be easily controlled through reaction conditions, thereby providing corresponding iodination or di-iodination products with high yields. Furthermore, these two reactions can be easily scaled up to gram-scale by using palladium catalyst (0.66 mol%), which provides high isolated yield. PMID:28091536

  16. 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

  17. Pancreatic Panniculitis in an 18-Month-Old with Complete DiGeorge Syndrome.

    PubMed

    Aivaz, Ohara; Radfar, Arash; Kirkorian, Anna Yasmine

    2016-05-01

    Pancreatic panniculitis, characterized by tender, erythematous subcutaneous nodules occurring most commonly on the lower extremities, occurs in 2% of cases of pancreatic disease. We present a rare case of pancreatic panniculitis in a child with complete DiGeorge syndrome.

  18. Isolation of a zinc finger gene consistently deleted in DiGeorge syndrome.

    PubMed

    Aubry, M; Demczuk, S; Desmaze, C; Aikem, M; Aurias, A; Julien, J P; Rouleau, G A

    1993-10-01

    DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of the thymus and parathyroids, and conotruncal heart defects. We recently isolated four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2 DiGeorge critical region. We now report that one of them, ZNF74 gene, is hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested. ZNF74 mRNA transcripts are detected in human and mouse embryos but not in adult tissues. Sequence analysis of a corresponding cDNA reveals an an open reading frame encoding 12 zinc finger motifs of the Kruppel/TFIIIA type as well as N-terminal and C-terminal non-zinc finger domains. These results suggest that changes in the dosage of a putative transcription factor through ZNF74 hemizygous deletion may be critical for DiGeorge developmental anomalies.

  19. Combination of diOlistic labeling with retrograde tract tracing and immunohistochemistry.

    PubMed

    Neely, M Diana; Stanwood, Gregg D; Deutch, Ariel Y

    2009-11-15

    Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. DiOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has recently been introduced as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the restricted use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies.

  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. Combination of DiOlistic Labeling with Retrograde Tract Tracing and Immunohistochemistry

    PubMed Central

    Diana Neely, M.; Stanwood, Gregg D; Deutch, Ariel Y.

    2009-01-01

    Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. Recently diOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has been developed as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies. PMID:19712695

  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. Features of Turner's and DiGeorge's syndromes in a child with an X;22 translocation.

    PubMed Central

    Pinto, M R; Leite, R P; Areias, A

    1989-01-01

    We describe the clinical and cytogenetic findings in an infant who presented with the features of both Turner's and DiGeorge's syndromes associated with a unique translocation between chromosomes X and 22. Images PMID:2614798

  4. Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

    PubMed Central

    Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Sitong; Bian, Tingwei; Han, Chunmao; Meng, Qin

    2016-01-01

    Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring. PMID:27901027

  5. Characterization of factors that transform linoleic acid into di- and trihydroxyoctadecenoic acids in mash.

    PubMed

    Kuroda, Hisao; Kobayashi, Naoyuki; Kaneda, Hirotaka; Watari, Junji; Takashio, Masachika

    2002-01-01

    The qualities of beer are deteriorated by the presence of either di- or trihydroxyoctadecenoic acids, which reduce the beer 'head' and produce an astringent flavor. In this study we found that native extracts of malt mash transformed linoleic acid into di- and trihydroxyoctadecenoic acids, but this transforming activity and lipoxygenase activity were inactivated by heating the mash at 70 degrees C for 30 min. Recombinant barley lipoxygenase 1 was not able to transform linoleic acid into di- and trihydroxyoctadecenoic acids. The transforming activity of mash extract heated at 70 degrees C for 30 min could be restored by the addition of recombinant barley lipoxygenase 1; in contrast, the activity of boiled mash extract was not substantially restored by the recombinant enzyme. These results indicate that di- and trihydroxyoctadecenoic acids are generated from linoleic acid by both lipoxygenase and a heat-stable enzymatic factor present in the mash.

  6. Expression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli

    PubMed Central

    Reinders, Alberto; Hee, Chee-Seng; Ozaki, Shogo; Mazur, Adam; Boehm, Alex; Schirmer, Tilman

    2015-01-01

    ABSTRACT Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of diguanylate cyclases and phosphodiesterases. The phosphodiesterase PdeH was identified as a key regulator of motility in Escherichia coli, while deletions of any of the other 12 genes encoding potential phosphodiesterases did not interfere with motility. To analyze the roles of E. coli phosphodiesterases, we demonstrated that most of these proteins are expressed under laboratory conditions. We next isolated suppressor mutations in six phosphodiesterase genes, which reinstate motility in the absence of PdeH by reducing cellular levels of c-di-GMP. Expression of all mutant alleles also led to a reduction of biofilm formation. Thus, all of these proteins are bona fide phosphodiesterases that are capable of interfering with different c-di-GMP-responsive output systems by affecting the global c-di-GMP pool. This argues that E. coli possesses several phosphodiesterases that are inactive under laboratory conditions because they lack appropriate input signals. Finally, one of these phosphodiesterases, PdeL, was studied in more detail. We demonstrated that this protein acts as a transcription factor to control its own expression. Motile suppressor alleles led to a strong increase of PdeL activity and elevated pdeL transcription, suggesting that enzymatic activity and transcriptional control are coupled. In agreement with this, we showed that overall cellular levels of c-di-GMP control pdeL transcription and that this control depends on PdeL itself. We thus propose that PdeL acts both as an enzyme and as a c-di-GMP sensor to couple transcriptional activity to the c-di-GMP status of the cell. IMPORTANCE Most bacteria possess multiple diguanylate cyclases and phosphodiesterases. Genetic studies have proposed that these enzymes show signaling specificity by contributing to distinct cellular processes without much cross talk. Thus, spatial

  7. Monitoring Changes of Tropical Extreme Rainfall Events Using Differential Absorption Barometric Radar (DiBAR)

    NASA Technical Reports Server (NTRS)

    Lin, Bing; Harrah, Steven; Lawrence, R. Wes; Hu, Yongxiang; Min, Qilong

    2015-01-01

    This work studies the potential of monitoring changes in tropical extreme rainfall events such as tropical storms from space using a Differential-absorption BArometric Radar (DiBAR) operating at 50-55 gigahertz O2 absorption band to remotely measure sea surface air pressure. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 5 millibars (approximately 1 millibar) under all weather conditions. With these sea level pressure measurements, the forecasts, analyses and understanding of these extreme events in both short and long time scales can be improved. Severe weathers, especially hurricanes, are listed as one of core areas that need improved observations and predictions in WCRP (World Climate Research Program) and NASA Decadal Survey (DS) and have major impacts on public safety and national security through disaster mitigation. Since the development of the DiBAR concept about a decade ago, our team has made substantial progress in advancing the concept. Our feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. We have developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with our instrumentation goals. Observational system simulation experiments for space DiBAR performance show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on tropical extreme rainfall weather and climate conditions.

  8. Aspiration pneumonia in the child with DiGeorge syndrome -A case report-

    PubMed Central

    Han, Yun-Joung

    2011-01-01

    DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests with variable clinical findings. Aspiration pneumonia can be a perioperative complication of great concern in this syndrome. In this report, we present a case of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He developed perioperative aspiration pneumonia but was managed successfully. PMID:21738851

  9. The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium.

    PubMed

    Chen, Zhi-hui; Schaap, Pauline

    2012-08-30

    Cyclic di-(3′:5′)-guanosine monophosphate (c-di-GMP) is a major prokaryote signalling intermediate that is synthesized by diguanylate cyclases and triggers sessility and biofilm formation. We detected the first eukaryote diguanylate cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium discoideum amoebas collect into aggregates, which first transform into migrating slugs and then into sessile fruiting structures. These structures consist of a spherical spore mass that is supported by a column of stalk cells and a basal disk. A polyketide, DIF-1, which induces stalk-like cells in vitro, was isolated earlier. However, its role in vivo proved recently to be restricted to basal disk formation. Here we show that the Dictyostelium diguanylate cyclase, DgcA, produces c-di-GMP as the morphogen responsible for stalk cell differentiation. Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and was expressed at the slug tip, which is the site of stalk cell differentiation. Disruption of the DgcA gene blocked the transition from slug migration to fructification and the expression of stalk genes. Fructification and stalk formation were restored by exposing DgcA-null slugs to wild-type secretion products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3′:5′)-adenosine monophosphate, induced stalk gene expression in dilute cell monolayers. Apart from identifying the long-elusive stalk-inducing morphogen, our work also identifies a role for c-di-GMP in eukaryotes.

  10. A post-translational, c-di-GMP-dependent mechanism regulating flagellar motility.

    PubMed

    Fang, Xin; Gomelsky, Mark

    2010-06-01

    Elevated levels of the second messenger cyclic dimeric GMP, c-di-GMP, promote transition of bacteria from single motile cells to surface-attached multicellular communities. Here we describe a post-translational mechanism by which c-di-GMP initiates this transition in enteric bacteria. High levels of c-di-GMP induce the counterclockwise bias in Escherichia coli flagellar rotation, which results in smooth swimming. Based on co-immunoprecipitation, two-hybrid and mutational analyses, the E. coli c-di-GMP receptor YcgR binds to the FliG subunit of the flagellum switch complex, and the YcgR-FliG interaction is strengthened by c-di-GMP. The central fragment of FliG binds to YcgR as well as to FliM, suggesting that YcgR-c-di-GMP biases flagellum rotation by altering FliG-FliM interactions. The c-di-GMP-induced smooth swimming promotes trapping of motile bacteria in semi-solid media and attachment of liquid-grown bacteria to solid surfaces, whereas c-di-GMP-dependent mechanisms not involving YcgR further facilitate surface attachment. The YcgR-FliG interaction is conserved in the enteric bacteria, and the N-terminal YcgR/PilZN domain of YcgR is required for this interaction. YcgR joins a growing list of proteins that regulate motility via the FliG subunit of the flagellum switch complex, which suggests that FliG is a common regulatory entryway that operates in parallel with the chemotaxis that utilizes the FliM-entryway.

  11. BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive transcription factor.

    PubMed

    Chambers, Jacob R; Liao, Julie; Schurr, Michael J; Sauer, Karin

    2014-05-01

    The transcriptional regulator BrlR is a member of the MerR family of multidrug transport activators that contributes to the high-level drug tolerance of Pseudomonas aeruginosa biofilms. While MerR regulators are known to activate both the expression of multidrug efflux pump genes and their own transcription upon inducer binding, little is known about BrlR activation. We demonstrate using promoter reporter strains, in vivo and in vitro DNA-binding assays combined with 5'RACE, that BrlR binds to its own promoter, likely via a MerR-like palindromic sequence. Unlike known MerR multidrug transport activators, BrlR and brlR expression are not activated by multidrug transporter substrates. Instead, BrlR-DNA binding was enhanced by the secondary messenger c-di-GMP. In addition to enhanced BrlR-DNA binding, c-di-GMP levels contributed to PbrlR promoter activity in initial attached cells with elevated c-di-GMP levels correlating with increased expression of brlR. While not harbouring amino acid motifs resembling previously defined c-di-GMP-binding domains, BrlR was found to bind c-di-GMP in vitro at a ratio of one c-di-GMP per two BrlR. Cross-linking assays confirmed dimer formation to be enhanced in the presence of elevated c-di-GMP levels. Our findings demonstrate BrlR to be an unusual MerR-family member in that BrlR function and expression require the secondary messenger c-di-GMP.

  12. BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive transcription factor

    PubMed Central

    Chambers, Jacob R.; Liao, Julie; Schurr, Michael J.; Sauer, Karin

    2014-01-01

    The transcriptional regulator BrlR is a member of the MerR family of multidrug transport activators that contributes to the high-level drug tolerance of Pseudomonas aeruginosa biofilms. While MerR regulators are known to activate both the expression of multidrug efflux pump genes and their own transcription upon inducer-binding, little is known about BrlR activation. We demonstrate using promoter reporter strains, in vivo and in vitro DNA-binding assays combined with 5’RACE, that BrlR binds to its own promoter, likely via a MerR-like palindromic sequence. Unlike known MerR multidrug transport activators, BrlR and brlR expression are not activated by multidrug transporter substrates. Instead, BrlR-DNA binding was enhanced by the secondary messenger c-di-GMP. In addition to enhanced BrlR-DNA binding, c-di-GMP levels contributed to PbrlR promoter activity in initial attached cells with elevated c-di-GMP levels correlating with increased expression of brlR. While not harboring amino acid motifs resembling previously defined c-di-GMP-binding domains, BrlR was found to bind c-di-GMP in vitro at a ratio of one c-di-GMP per two BrlR. Crosslinking assays confirmed dimer formation to be enhanced in the presence of elevated c-di-GMP levels. Our findings demonstrate BrlR to be an unusual MerR-family member in that BrlR function and expression require the secondary messenger c-di-GMP. PMID:24612375

  13. 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.

  14. The carcinogenicity of di(2-ethylhexyl) phthalate (DEHP) in perspective.

    PubMed

    Kluwe, W M; Haseman, J K; Huff, J E

    1983-07-01

    The commonly used plasticizer di(2-ethylhexyl) phthalate (DEHP) was recently tested for chronic toxic potential by incorporation into the diet of rats and mice for approximately 2 yr. Upon reviewing the test results, the sponsoring organization concluded that DEHP was carcinogenic to the rats and mice, as indicated by increased occurrences of liver tumors in the DEHP-exposed animals in comparison to controls. Another group has disagreed with this conclusion, however, citing perceived methodological deficiencies and improper interpretations in the study, and has also suggested that rodents may not be adequate models of human response to DEHP. This communication compares the conduct of the DEHP bioassay favorably with state-of-the-art procedures in animal carcinogenicity testing and documents approval of the study interpretations by several independent peer review groups. The carcinogenic potential of DEHP is placed in perspective by evaluating the evidence for DEHP-induced tumors in rodent species in light of dose response relationships, other biochemical and toxicological effects of DEHP, and its comparative metabolism and disposition in rodent and primate species. A composite analysis of the currently available information indicates that DEHP has been shown to be carcinogenic to rodents in a valid chronic test, indicating that it should be considered as a potential carcinogen in humans, as well. Further experimental inquiry will be required, however, to accurately assess the potential health risks posed to humans by exposure to small amounts of this plasticizer.

  15. Absence of genomic imprinting at the DiGeorge locus

    SciTech Connect

    Theophile, D.; Berube, D.; Auge, J.; Vekemans, M.

    1994-09-01

    In situ hybridization with fluorescence probes (FISH) on interphase nuclei allows evaluation of the stage of DNA replication. For example, in a diploid cell in G1, unreplicated DNA gives two single dots of hybridization whereas in a diploid cell in G2, for loci which have already replicated, the hybridization signal is seen as two pairs of doublets. In contrast, sequences which have an asynchronous replication are characterized by one double hybridization signal and one single hybridization signal. It has been shown recently that sequences subject to genomic imprinting have an asynchronous replication, i.e., the two homologous alleles have a different pattern of replication. We have tested the replication pattern of different sequences of the DiGeorge critical region using FISH. The results obtained with probes 48F8, C350, C237 and COS40 show no evidence of asynchronous replication. This suggests that these loci are not subject to imprinting. These results are in agreement with recent observation of cases of uniparental disomy of chromosome 22 without phenotypic features. Further studies are necessary to exclude other regions of chromosome 22 which might be subject to genomic imprinting.

  16. DiI cell labeling in lamprey embryos.

    PubMed

    Nikitina, Natalya; Bronner-Fraser, Marianne; Sauka-Spengler, Tatjana

    2009-01-01

    Lampreys are one of the most basal animals in which many of the true vertebrate characteristics (e.g., neural crest, placodes, segmented brain, skull, paired sensory organs, pharyngeal skeleton) are present. Studying the molecular and developmental mechanisms responsible for the formation of these structures in lamprey and higher vertebrates can provide insight into how these vertebrate characteristics evolved. The relative ease of obtaining mature adults and embryos makes this animal an ideal model for investigations into early vertebrate evolution. In addition, studies of features that are unique to lampreys can provide insights into mechanisms of parallel evolution. Lamprey embryos are particularly amenable to injection techniques. Like zebrafish and Xenopus embryos, they have double chorions and are resistant to surface-tension-induced rupture when removed from liquid. They can therefore be injected in a dry dish; this eliminates the need to support the embryo while performing injections and makes the procedure very rapid. Also, a single ovulating female can contain up to 100,000 eggs, so the number of injectable embryos per fertilization is not a limiting factor. This protocol describes how to label lamprey embryo cells by microinjecting the fluorescent dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) to study cell fate during development.

  17. Clinical and molecular study of DiGeorge sequence.

    PubMed

    Levy-Mozziconacci, A; Wernert, F; Scambler, P; Rouault, F; Metras, D; Kreitman, B; Depetris, D; Mattei, M G; Philip, N

    1994-11-01

    DiGeorge sequence (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. The cardinal features of the syndrome are hypo- or aplasia of the thymus and parathyroids, congenital heart defect of the conotruncal type and characteristic facial dysmorphism. Such a pattern of malformations has been associated with various conditions but it is now well established that most cases of DGS are due to haplo-insufficiency of the chromosome 22q11 region. We report here a series of 16 patients, including a familial case. Minimal criteria for inclusion in this series were two or more of the following features: conotruncal heart defect, hypocalcaemia, hypoplastic/absent thymus and typical facial dysmorphism. Molecular analysis with specific probes of the 22q11 region was conducted in all patients according to two methods, fluorescent in situ hybridization and DNA dosage analysis. A deletion was found at the molecular level in all patients. We emphasize the fact that clinical analysis remains an important step of the diagnosis. The implication of these molecular techniques on diagnosis, prognosis and genetic counselling of DGS are discussed.

  18. 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.

  19. Competition in di- and tri-trophic food web modules.

    PubMed

    Křivan, Vlastimil

    2014-02-21

    Competition in di- and tri-trophic food web modules with many competing species is studied. The food web modules considered are apparent competition between n species sharing a single predator and a diamond-like food web with a single resource, a single top predator and many competing middle species. The predators have either fixed preferences for their prey, or they switch between available prey in a way that maximizes their fitness. Dependence of these food web dynamics on environmental carrying capacity and food web connectance is studied. The results predict that optimal flexible foraging strongly weakens apparent competition and promotes species coexistence. Food web robustness (defined here as the proportion of surviving species) does not decrease with increased connectance in these food-webs. Moreover, it is shown that flexible prey switching leads to the same population equilibria as in corresponding food webs with highly specialized predators. The results show that flexible foraging behavior by predators can have very strong impact on species richness, as well as the response of communities to changes in resource enrichment and food-web connectance when compared to the same food-web topology with inflexible top predators. Several results on global stability using Lyapunov functions are provided. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Mono-, Di-, or Trimorphism in Black Sea Ammonia sp.

    NASA Astrophysics Data System (ADS)

    Altenbach, Alexander V.; Bassler, Barbara

    2014-05-01

    For the genus Ammonia, the size of proloculi was considered one of the valuable taxonomic landmarks, although it may split in first alternating generations. We analysed 140 living (stained) tests of Ammonia sp. from the outer shelf of the Black Sea, collected from 5 stations on a depth gradient (138 to 206 m water depth). Samples were treated by standard technologies, such as live staining, wet sieving, volume detection, counts, and measures by light microscopy. The size of the proloculi was detected, extended by biometric characterisations of 11 measures, 5 qualitative characters, and 4 numerical ratios. Surprisingly, the multitude of test parameters allows the definition of either one highly variable taxon, or several species, or either di- or trimorphism, exclusively resulting from the definition of 'decisive' or 'neglectable' parameters, or parameter subsets. We followed the general taxonomic definition for the species of the genera, and applied, discussed and rejected published criteria considered as taxonomically important. Surprisingly, in result none of the species described hitherto fully correlates with the morphological roundup observed. It is a new species. This conclusion mainly results from the balance of all morphologies, and not from the selection of an ultimate subset.

  2. Thermochromic transitions in poly(di- n-hexylsilane) films

    NASA Astrophysics Data System (ADS)

    Ostapenko, N. I.; Zaika, V.; Suto, S.; Watanabe, A.

    2004-07-01

    The spectra of absorption (77-398 K) and luminescence (5 K) of poly(di- n-hexylsilane) films are studied in relation to the heating of the films above the phase transition temperature. Two new absorption bands in the region of the band of the gauche conformation are found. The position and intensity of these bands depend on the annealing temperature, annealing regime, and sample thickness. These bands are assumed to be associated with the appearance of a liquid crystalline phase in the polymer, which is determined by intermolecular interactions between neighboring polymer chains. The appearance of the liquid crystalline phase in the heat-treated polymer films is confirmed by the increase in their birefringence in comparison with the birefringence of the initial films and by the observation of a stable orientation of an E 7 nematic liquid crystal applied to the surface of an annealed sample. In addition, the absorption spectra of the films cooled after the annealing exhibit many new bands in comparison with the spectra of the initial samples. These bands are associated with the appearance in the polymer of defect states and longer segments as a result of orientation of polymer chains. The appearance of longer segments is consistent with the observation of a long-wavelength band in the luminescence spectra of the annealed samples.

  3. 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

  4. DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum.

    PubMed

    Saltman, Anna J; Barakat, May; Bryant, Donald M; Brodovskaya, Anastasia; Whited, Jessica L

    2017-06-16

    Perfusion techniques have been used for centuries to visualize the circulation of tissues. Axolotl (Ambystoma mexicanum) is a species of salamander that has emerged as an essential model for regeneration studies. Little is known about how revascularization occurs in the context of regeneration in these animals. Here we report a simple method for visualization of the vasculature in axolotl via perfusion of 1,1'-Dioctadecy-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). DiI is a lipophilic carbocyanine dye that inserts into the plasma membrane of endothelial cells instantaneously. Perfusion is done using a peristaltic pump such that DiI enters the circulation through the aorta. During perfusion, dye flows through the axolotl's blood vessels and incorporates into the lipid bilayer of vascular endothelial cells upon contact. The perfusion procedure takes approximately one hour for an eight-inch axolotl. Immediately after perfusion with DiI, the axolotl can be visualized with a confocal fluorescent microscope. The DiI emits light in the red-orange range when excited with a green fluorescent filter. This DiI perfusion procedure can be used to visualize the vascular structure of axolotls or to demonstrate patterns of revascularization in regenerating tissues.

  5. 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

  6. DiNAMIC: a method to identify recurrent DNA copy number aberrations in tumors

    PubMed Central

    Walter, Vonn; Nobel, Andrew B.; Wright, Fred A.

    2011-01-01

    Motivation: DNA copy number gains and losses are commonly found in tumor tissue, and some of these aberrations play a role in tumor genesis and development. Although high resolution DNA copy number data can be obtained using array-based techniques, no single method is widely used to distinguish between recurrent and sporadic copy number aberrations. Results: Here we introduce Discovering Copy Number Aberrations Manifested In Cancer (DiNAMIC), a novel method for assessing the statistical significance of recurrent copy number aberrations. In contrast to competing procedures, the testing procedure underlying DiNAMIC is carefully motivated, and employs a novel cyclic permutation scheme. Extensive simulation studies show that DiNAMIC controls false positive discoveries in a variety of realistic scenarios. We use DiNAMIC to analyze two publicly available tumor datasets, and our results show that DiNAMIC detects multiple loci that have biological relevance. Availability: Source code implemented in R, as well as text files containing examples and sample datasets are available at http://www.bios.unc.edu/research/genomic_software/DiNAMIC. Contact: vwalter@email.unc.edu; fwright@bios.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21183584

  7. Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.

    PubMed

    Forner-Piquer, Isabel; Maradonna, Francesca; Gioacchini, Giorgia; Santangeli, Stefania; Allarà, Marco; Piscitelli, Fabiana; Habibi, Hamid R; Di Marzo, Vincenzo; Carnevali, Oliana

    2017-10-01

    Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. Copyright © 2017 Endocrine Society.

  8. Synthesis, structures and charge-transfer complexations of 1,n-di-[3,6-di-(9-carbazolyl)-9-carbazolyl]alkanes with tetracyanoethylene and tetranitromethane

    NASA Astrophysics Data System (ADS)

    Özgün, Selin; Asker, Erol; Zeybek, Orhan

    2017-01-01

    Synthesis and charge-transfer (CT) complexations of amorphous 3,6-di-(9-carbazolyl)-9-ethylcarbazole, 3,6-di-(9-carbazolyl)-9-hexylcarbazole and a series of 1,n-di-[3,6-di-(9-carbazolyl)-9-carbazolyl]alkanes (n = 1-5) with electron acceptors tetracyanoethylene and tetranitromethane are reported. The molar extinction coefficients (ε), equilibrium constants (Keq), enthalpies (ΔH) and entropies (ΔS) of complexations have been determined. The low Keq values (1.83-3.82 M-1 for carbazole-TCNE and 0.28-0.45 M-1 for carbazole-TNM complexes) show weak donor-acceptor associations. The negative values of ΔH determined to be between -2.09 ± 0.08 and -3.10 ± 0.21 kcal mol-1 for carbazole-TCNE complexes and -0.91 ± 0.08 and -3.31 ± 0.28 kcal mol-1 for carbazole-TNM complexes indicate that complexations are driven by the exothermic enthalpies. Computational analysis using semi-empirical and DFT methods were applied to clarify the structures of the synthesized molecules and the nature of their CT complexations.

  9. 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.

  10. [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.

  11. 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.

  12. Structures of di-substituted and charged cavitands

    NASA Astrophysics Data System (ADS)

    Aniol, Alexandra; Mallick, Bert; Winter, Manuela; Feigel, Martin

    2017-09-01

    Calix[4]resorcinarene based cavitands build from resorcinol or 2-methylresorcinol were synthesized with a focus on systems having less than four substituents at the upper rim. The structures of the synthesized di-substituted calix[4]resorcinarenes, 2 (5,17-Dibromo-4(24),6(10),12(16),18(22)-tetramethylendioxy-2,8,14,20-tetrapentylresorcin[4]arene) and 4 (5,11-Bis[urotropinyliummethyl]-17,23-dimethyl-4(24),6(10),12(16),18(22)-tetramethylendioxy-2,8,14,20-tetrapentylresorcin[4]arene-dibromide), together with the tetra-substituted calix[4]resorcinarene 1 (5,11,17,23-Tetrabromo-4(24),6(10),12(16),18(22)-tetramethylendioxy-2,8,14,20-tetrapentylresorcin[4]arene) were investigated via 1H, 13C NMR and X-ray single crystal diffraction. The stereochemistry of the anti-dibromo-resorcinarene-cavitand 2 and of the syn-bis(urotropinyliummethyl)-cavitand 4 was anticipated by their NMR-data and is confirmed by X-ray derived structures. Small solvent molecules (n-pentane and chloroform resp.) are included in the resorcinarene cavities of 1, 2 and 4. Compound 4 builds a crystal in which polar layers of the substituents at the upper rim of the cavitand, consisting of the charged urotropinyl units and their bromide counter ions, alternate with lipophilic layers filled with the pentyl chains at the lower rim of the cavitand. So a multiple bilayer structure is formed via head to head and tail to tail arrangements as found in the crystal structures of membrane lipids.

  13. 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.

  14. Structural and biochemical determinants of ligand binding by the c-di-GMP riboswitch†,‡

    PubMed Central

    Smith, Kathryn D.; Lipchock, Sarah V.; Livingston, Alison L.; Shanahan, Carly A.; Strobel, Scott A.

    2011-01-01

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that the most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high resolution (2.3 Å) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3′-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation. PMID:20690679

  15. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Replenishing the cyclic-di-AMP pool: regulation of diadenylate cyclase activity in bacteria.

    PubMed

    Pham, Thi Huong; Liang, Zhao-Xun; Marcellin, Esteban; Turner, Mark S

    2016-11-01

    Bacteria can sense environmental cues and alter their physiology accordingly through the use of signal transduction pathways involving second messenger nucleotides. One broadly conserved second messenger is cyclic-di-AMP (c-di-AMP) which regulates a range of processes including cell wall homeostasis, potassium uptake, DNA repair, fatty acid synthesis, biofilm formation and central metabolism in bacteria. The intracellular pool of c-di-AMP is maintained by the activities of diadenylate cyclase (DAC) and phosphodiesterase (PDE) enzymes, as well as possibly via c-di-AMP export. Whilst extracellular stimuli regulating c-di-AMP levels in bacteria are poorly understood, recent work has identified effector proteins which directly interact and alter the activity of DACs. These include the membrane bound CdaR and the phosphoglucosamine mutase GlmM which both bind directly to the membrane bound CdaA DAC and the recombination protein RadA which binds directly to the DNA binding DisA DAC. The genes encoding these multiprotein complexes are co-localised in many bacteria providing further support for their functional connection. The roles of GlmM in peptidoglycan synthesis and RadA in Holliday junction intermediate processing suggest that c-di-AMP synthesis by DACs will be responsive to these cellular activities. In addition to these modulatory interactions, permanent dysregulation of DAC activity due to suppressor mutations can occur during selection to overcome growth defects, rapid cell lysis and osmosensitivity. DACs have also been investigated as targets for the development of new antibiotics and several small compound inhibitors have recently been identified. This review aims to provide an overview of how c-di-AMP synthesis by DACs can be regulated.

  17. A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP.

    PubMed

    Commichau, Fabian M; Dickmanns, Achim; Gundlach, Jan; Ficner, Ralf; Stülke, Jörg

    2015-07-01

    Second messengers are key components of many signal transduction pathways. In addition to cyclic AMP, ppGpp and cyclic di-GMP, many bacteria use also cyclic di-AMP as a second messenger. This molecule is synthesized by distinct classes of diadenylate cyclases and degraded by phosphodiesterases. The control of the intracellular c-di-AMP pool is very important since both a lack of this molecule and its accumulation can inhibit growth of the bacteria. In many firmicutes, c-di-AMP is essential, making it the only known essential second messenger. Cyclic di-AMP is implicated in a variety of functions in the cell, including cell wall metabolism, potassium homeostasis, DNA repair and the control of gene expression. To understand the molecular mechanisms behind these functions, targets of c-di-AMP have been identified and characterized. Interestingly, c-di-AMP can bind both proteins and RNA molecules. Several proteins that interact with c-di-AMP are required to control the intracellular potassium concentration. In Bacillus subtilis, c-di-AMP also binds a riboswitch that controls the expression of a potassium transporter. Thus, c-di-AMP is the only known second messenger that controls a biological process by interacting with both a protein and the riboswitch that regulates its expression. Moreover, in Listeria monocytogenes c-di-AMP controls the activity of pyruvate carboxylase, an enzyme that is required to replenish the citric acid cycle. Here, we review the components of the c-di-AMP signaling system.

  18. The Effect of Diethylene Glycol Monomethyl Ether (DiEGME) on Microbial Contamination of Jet Fuel: A Minimum Concentration Study

    DTIC Science & Technology

    2010-03-01

    suggests that a minimum of ~0.01-0.02% DiEGME is needed to retain biocidal/biostatic effectiveness. See Alternate Abstract on reverse 15...ii 14. ABSTRACT ( alternate ) Diethylene glycol monomethyl ether (DiEGME) is widely used in military aircraft as a fuel system icing inhibitor...investigation into the effects of alternate filter types, flow passage sizes, overall flow rate, and total filtration surface areas. Thus far, DiEGME

  19. A C-di-GMP-proflavine-hemin supramolecular complex has peroxidase activity--implication for a simple colorimetric detection.

    PubMed

    Nakayama, Shizuka; Roelofs, Kevin; Lee, Vincent T; Sintim, Herman O

    2012-03-01

    Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) and hence provides simple colorimetric detection of c-di-GMP at low micromolar concentrations.

  20. Comparison of anti-bacterial activity of three types of di-O-caffeoylquinic acids in Lonicera japonica flowers based on microcalorimetry.

    PubMed

    Han, Jin; Lv, Qing-Yuan; Jin, Shi-Ying; Zhang, Tian-Tian; Jin, Shi-Xiao; Li, Xian-Yi; Yuan, Hai-Long

    2014-02-01

    The anti-bacterial activities of three types of di-O-caffeoylquinic acids (diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine (TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid (3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid (3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid (4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power-time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs (IC50) were obtained by quantitative analysis. Based on the quantity-activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.

  1. Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor

    PubMed Central

    Hickman, Jason W.; Harwood, Caroline S.

    2008-01-01

    High levels of the intracellular signaling molecule cyclic diguanylate (c-di-GMP) supress motility and activate exopolysaccharide (EPS) production in a variety of bacterial species. In many bacteria part of the effect of c-di-GMP is on gene expression, but the mechanism involved is not known for any species. We have identified the protein FleQ as a c-di-GMP-responsive transcriptional regulator in Pseudomonas aeruginosa. FleQ is known to activate expression of flagella biosynthesis genes. Here we show that it also represses transcription of genes including the pel operon involved in EPS biosynthesis, and that this repression is relieved by c-di-GMP. Our in vivo data indicate that FleQ represses pel transcription and that pel transcription is not repressed when intracellular c-di-GMP levels are high. FleN, a known antiactivator of FleQ also participates in control of pel expression. In in vitro experiments we found that FleQ binds to pel promoter DNA and that this binding is inhibited by c-di-GMP. FleQ binds radiolabeled c-di-GMP in vitro. FleQ does not have amino acid motifs that resemble previously defined c-di-GMP binding domains. Our results show that FleQ is a new type of c-di-GMP binding protein that controls the transcriptional regulation of EPS biosynthesis genes in P. aeruginosa. PMID:18485075

  2. 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.

  3. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    PubMed

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. 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

  5. Theoretical study of the substituent effect on the intramolecular hydrogen bonds in di(4-hydroxycoumarin) derivatives

    NASA Astrophysics Data System (ADS)

    Mihaylov, Tzvetan; Georgieva, Ivelina; Bauer, Günther; Kostova, Irena; Manolov, Ilia; Trendafilova, Natasha

    Geometry optimization of ortho-, meta-, and para-pyridyl-substituted di(4-hydroxycoumarin) [di(4-HC)] was performed with the density functional theory (DFT) [B3LYP/6-31G(d)] method. Two asymmetrical intramolecular O bond H?O hydrogen bonds (HBs) stabilized the structures. The calculated single HB energies varied from -62.56 to -47.53 kJ mol-1 and pointed to a relative strong hydrogen bond in the systems studied. The 2- and 6-pyridyl substituents produced the largest geometrical changes in di(4-hydroxycoumarin) fragment. The highest total HB energy was found for 2-pyridyl-substituted and the lowest one for 6-pyridyl-substituted di(4-hydroxycoumarin). The HB energy variations were confirmed with rotational barrier method calculations. Both steric and electrostatic factors were found to be responsible for the HB asymmetry in the compounds studied. According to the molecular electrostatic potential (MEP) calculations the most preferred reactive site for electrophilic attack of pyridyl-substituted di(4-hydroxycoumarin)s are the pyridine nitrogen and the carbonyl oxygens, followed by the hydroxyl oxygens.

  6. Temperature affects c-di-GMP signaling and biofilm formation in Vibrio cholerae

    PubMed Central

    Townsley, Loni; Yildiz, Fitnat H.

    2016-01-01

    SUMMARY 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 signaling molecule, cyclic diguanylate (c-di-GMP). Strains harboring 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 (VPS) 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 signaling. PMID:25684220

  7. 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.

  8. Engineering a novel c-di-GMP-binding protein for biofilm dispersal.

    PubMed

    Ma, Qun; Yang, Zhonghua; Pu, Mingming; Peti, Wolfgang; Wood, Thomas K

    2011-03-01

    Bacteria prefer to grow attached to themselves or an interface, and it is important for an array of applications to make biofilms disperse. Here we report simultaneously the discovery and protein engineering of BdcA (formerly YjgI) for biofilm dispersal using the universal signal 3,5-cyclic diguanylic acid (c-di-GMP). The bdcA deletion reduced biofilm dispersal, and production of BdcA increased biofilm dispersal to wild-type level. Since BdcA increases motility and extracellular DNA production while decreasing exopolysaccharide, cell length and aggregation, we reasoned that BdcA decreases the concentration of c-di-GMP, the intracellular messenger that controls cell motility through flagellar rotation and biofilm formation through synthesis of curli and cellulose. Consistently, c-di-GMP levels increase upon deleting bdcA, and purified BdcA binds c-di-GMP but does not act as a phosphodiesterase. Additionally, BdcR (formerly YjgJ) is a negative regulator of bdcA. To increase biofilm dispersal, we used protein engineering to evolve BdcA for greater c-di-GMP binding and found that the single amino acid change E50Q causes nearly complete removal of biofilms via dispersal without affecting initial biofilm formation. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  9. Production and structure elucidation of di- and oligosaccharide lipids (biosurfactants) from Tsukamurella sp. nov.

    PubMed

    Vollbrecht, E; Heckmann, R; Wray, V; Nimtz, M; Lang, S

    1998-11-01

    The bacterium Tsukamurella sp. nov., isolated from soil, was found to produce novel glycolipids when grown on sunflower oil as the sole carbon source. The glycolipids were isolated by chromatography on silica columns and their structures elucidated using a combination of multidimensional NMR and MS techniques. The three main components are 2,3-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D-glucopyranose, 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-4,6-di-O-acyl-alpha-D- glucopyranosyl-(1-1)-alpha-D-glucopyranose and 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-beta-D-galactopyranosyl- (1-6)-4,6-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D- glucopyranosyl which are linked to fatty acids varying in chain length from C4 to C18. The glycolipids are mainly extracellular but are also found attached to the cell walls. During the cultivation the composition of the glycolipids changed from disaccharide- to tri- and tetrasaccharide lipids. The glycolipids show good surface-active behaviour and have antimicrobial properties.

  10. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome.

    PubMed

    Voss, Anne K; Vanyai, Hannah K; Collin, Caitlin; Dixon, Mathew P; McLennan, Tamara J; Sheikh, Bilal N; Scambler, Peter; Thomas, Tim

    2012-09-11

    DiGeorge syndrome, caused by a 22q11 microdeletion or mutation of the TBX1 gene, varies in severity greatly, even among monozygotic twins. Epigenetic phenomena have been invoked to explain phenotypic differences in individuals of identical genetic composition, although specific chromatin modifications relevant to DiGeorge syndrome are elusive. Here we show that lack of the histone acetyltransferase MOZ (MYST3/KAT6A) phenocopies DiGeorge syndrome, and the MOZ complex occupies the Tbx1 locus, promoting its expression and histone 3 lysine 9 acetylation. Importantly, DiGeorge syndrome-like anomalies are present in mice with homozygous mutation of Moz and in heterozygous Moz mutants when combined with Tbx1 haploinsufficiency or oversupply of retinoic acid. Conversely, a Tbx1 transgene rescues the heart phenotype in Moz mutants. Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome.

  11. Tetrameric c-di-GMP Mediates Effective Transcription Factor Dimerization to Control Streptomyces Development

    PubMed Central

    Tschowri, Natalia; Schumacher, Maria A.; Schlimpert, Susan; Chinnam, Naga babu; Findlay, Kim C.; Brennan, Richard G.; Buttner, Mark J.

    2014-01-01

    Summary The cyclic dinucleotide c-di-GMP is a signaling molecule with diverse functions in cellular physiology. Here, we report that c-di-GMP can assemble into a tetramer that mediates the effective dimerization of a transcription factor, BldD, which controls the progression of multicellular differentiation in sporulating actinomycete bacteria. BldD represses expression of sporulation genes during vegetative growth in a manner that depends on c-di-GMP-mediated dimerization. Structural and biochemical analyses show that tetrameric c-di-GMP links two subunits of BldD through their C-terminal domains, which are otherwise separated by ∼10 Å and thus cannot effect dimerization directly. Binding of the c-di-GMP tetramer by BldD is selective and requires a bipartite RXD-X8-RXXD signature. The findings indicate a unique mechanism of protein dimerization and the ability of nucleotide signaling molecules to assume alternative oligomeric states to effect different functions. PMID:25171413

  12. 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.

  13. 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

    2015-04-07

    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.

  14. 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.

  15. 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. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. [Dao-di herbs and its change of cultivated origin place].

    PubMed

    Meng, Xiangcai; Chen, Shilin; Wang, Xijun

    2011-07-01

    The origin place change is an almost universal rule for many Chinese medicines according to the formation and change history of ancient and recent Dao-di herbs. Among them, the quality and output are the essence and driving force of the formation and change of Dao-di herbs origin place. More and more species and quantities of Chinese medicine were cultivated along with development of Chinese medicine and modern manufacturing technology, and its production regions far exceed natural location zones, the rationality of origin place change should be based on drug quality evaluation. Under the guidance of the formation mode of Dao-di herbs, characteristics of Dao-di herbs were summarized, its characteristics and applied limits were suggested, some traditional Chinese medicinal materials only with higher output, cultivated materials in distribution area for wild, or materials with poor genetic resources failing to answer with Dao-di herbs. Chinese medicines authenticity should strengthen the study of germplasm and drug quality assessment, the suitability of producing area should be assessed according to output and quality under the guidance of suitable locations regionalization.

  17. 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.

  18. Disintegration of aerobic granules: role of second messenger cyclic di-GMP.

    PubMed

    Wan, Chunli; Zhang, Peng; Lee, Duu-Jong; Yang, Xue; Liu, Xiang; Sun, Supu; Pan, Xiangliang

    2013-10-01

    Loss of structural stability of aerobic granular process is the challenge for its field applications to treat wastewaters. The second messenger, cyclic diguanylate (c-di-GMP), is widely used by bacteria to regulate the synthesis of exopolysaccharide. This study for the first time confirmed the correlation between concentration of intracellular c-di-GMP and the granular stability under sequencing batch reactor (MBR) mode. In the presence of manganese ions (Mn(2+)), the concentrations of intracellular c-di-GMP and of extracellular polysaccharides and proteins in granules were declined. Clone library study revealed that the polysaccharide producers. Acinetobacter sp., Thauera sp., Bdellovibrio sp. and Paracoccus sp. were lost after Mn(2+) addition. The findings reported herein confirmed that the c-di-GMP is a key chemical factor epistatic to quorum sensing to determine granular stability. Stimulation of synthesis of intracellular c-di-GMP presents a potential way to enhance long-term stability of aerobic granules. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Biosynthesis of di-rhamnolipids and variations of congeners composition in genetically-engineered Escherichia coli.

    PubMed

    Du, Jin; Zhang, Aijun; Hao, Jian'an; Wang, Jing

    2017-07-01

    To engineer Escherichia coli for the heterologous production of di-rhamnolipids, which are important biosurfactants but mainly produced by opportunistic pathogen Pseudomonas aeruginosa. The codon-optimized rhlAB and rhlC genes originating from P. aeruginosa and Burkholderia pseudomallei were combinatorially expressed in E. coli to produce di-rhamnolipids with varied congeners compositions. Genes involved in endogenous upstream pathways (rhamnose and fatty acids synthesis) were co-overexpressed with rhlAB-rhlC, resulting in variations of rhamnolipids production and congeners compositions. Under the shake-flask condition, co-overexpression of rfbD with rhlAB-rhlC increased rhamnolipids production (0.64 ± 0.02 g l(-1)) than that in strain only expressing rhlAB-rhlC (0.446 ± 0.009 g l(-1)), which was mainly composed of di-rhamnolipids congeners Rha-Rha-C10-C10. Biosynthesis of di-rhamnolipids and variations of congeners composition in genetically engineered E. coli strains were achieved via combiniations of mono-/di-rhamnolipids synthesis modules and endogenous upstream modules.

  20. Capture Compound Mass Spectrometry - A Powerful Tool to Identify Novel c-di-GMP Effector Proteins

    PubMed Central

    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 organisms1. 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. PMID:25867682

  1. 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

  2. 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

  3. Thymus transplantation for complete DiGeorge syndrome: European experience.

    PubMed

    Davies, E Graham; Cheung, Melissa; Gilmour, Kimberly; Maimaris, Jesmeen; Curry, Joe; Furmanski, Anna; Sebire, Neil; Halliday, Neil; Mengrelis, Konstantinos; Adams, Stuart; Bernatoniene, Jolanta; Bremner, Ronald; Browning, Michael; Devlin, Blythe; Erichsen, Hans Christian; Gaspar, H Bobby; Hutchison, Lizzie; Ip, Winnie; Ifversen, Marianne; Leahy, T Ronan; McCarthy, Elizabeth; Moshous, Despina; Neuling, Kim; Pac, Malgorzata; Papadopol, Alina; Parsley, Kathryn L; Poliani, Luigi; Ricciardelli, Ida; Sansom, David M; Voor, Tiia; Worth, Austen; Crompton, Tessa; Markert, M Louise; Thrasher, Adrian J

    2017-04-08

    Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. We sought to confirm and extend the results previously obtained in a single center. Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10(6)/L (range, 11-440 × 10(6)/L) and 200 × 10(6)/L (range, 5-310 × 10(6)/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10(6) T cells (range, 320-8,807/10(6) T cells) and 4,184/10(6) T cells (range, 1,582-24,596/10(6) T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors. Copyright © 2017 The Authors

  4. 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.

  5. 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

  6. GIL, a new c-di-GMP-binding protein domain involved in regulation of cellulose synthesis in enterobacteria.

    PubMed

    Fang, Xin; Ahmad, Irfan; Blanka, Andrea; Schottkowski, Marco; Cimdins, Annika; Galperin, Michael Y; Römling, Ute; Gomelsky, Mark

    2014-08-01

    In contrast to numerous enzymes involved in c-di-GMP synthesis and degradation in enterobacteria, only a handful of c-di-GMP receptors/effectors have been identified. In search of new c-di-GMP receptors, we screened the Escherichia coli ASKA overexpression gene library using the Differential Radial Capillary Action of Ligand Assay (DRaCALA) with fluorescently and radioisotope-labelled c-di-GMP. We uncovered three new candidate c-di-GMP receptors in E. coli and characterized one of them, BcsE. The bcsE gene is encoded in cellulose synthase operons in representatives of Gammaproteobacteria and Betaproteobacteria. The purified BcsE proteins from E. coli, Salmonella enterica and Klebsiella pneumoniae bind c-di-GMP via the domain of unknown function, DUF2819, which is hereby designated GIL, GGDEF I-site like domain. The RxGD motif of the GIL domain is required for c-di-GMP binding, similar to the c-di-GMP-binding I-site of the diguanylate cyclase GGDEF domain. Thus, GIL is the second protein domain, after PilZ, dedicated to c-di-GMP-binding. We show that in S. enterica, BcsE is not essential for cellulose synthesis but is required for maximal cellulose production, and that c-di-GMP binding is critical for BcsE function. It appears that cellulose production in enterobacteria is controlled by a two-tiered c-di-GMP-dependent system involving BcsE and the PilZ domain containing glycosyltransferase BcsA.

  7. Crystal structure of seleno-l-cystine di-hydro-chloride.

    PubMed

    Görbitz, Carl Henrik; Levchenko, Vladimir; Semjonovs, Jevgenijs; Sharif, Mohamed Yusuf

    2015-06-01

    Numerous crystal structures are available for the dimeric amino acid cystine. In proteins it is formed by oxidation of the -SH thiol groups of two closely spaced cysteine residues, resulting in the formation of a familiar di-sulfide bridge. The title compound [systematic name: (R,R)-1,1'-dicarb-oxy-2,2'-(diselanedi-yl)diethanaminium dichloride], C6H14N2O4Se2 (2+)·2Cl(-), is the first example of a small mol-ecule structure of the biologically important analogue with a -CH2-Se-Se-CH2- bridging unit. Bond lengths and angles of seleno-l-cystine di-hydro-chloride and its isotypic sulfur analogue l-cystine di-hydro-chloride are compared.

  8. Crystal structure of seleno-l-cystine di­hydro­chloride

    PubMed Central

    Görbitz, Carl Henrik; Levchenko, Vladimir; Semjonovs, Jevgenijs; Sharif, Mohamed Yusuf

    2015-01-01

    Numerous crystal structures are available for the dimeric amino acid cystine. In proteins it is formed by oxidation of the –SH thiol groups of two closely spaced cysteine residues, resulting in the formation of a familiar di­sulfide bridge. The title compound [systematic name: (R,R)-1,1′-dicarb­oxy-2,2′-(diselanedi­yl)diethanaminium dichloride], C6H14N2O4Se2 2+·2Cl−, is the first example of a small mol­ecule structure of the biologically important analogue with a —CH2—Se—Se—CH2— bridging unit. Bond lengths and angles of seleno-l-cystine di­hydro­chloride and its isotypic sulfur analogue l-cystine di­hydro­chloride are compared. PMID:26090162

  9. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Inherited t(9;22) as the cause of DiGeorge syndrome: a case report.

    PubMed

    Shuib, Salwati; Abdul Latif, Zarina; Abidin, Nor Zarina Zainal; Akmal, Sharifah Noor; Zakaria, Zubaidah

    2009-12-01

    DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur sporadically although vertical transmission has been documented. We report a rare case of DiGeorge syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following standard procedure. All of the 20 cells analysed showed a karyotype of 45, XX, -22, t (9;22) (p23; q11.2). Cytogenetic investigation done on the patient's mother revealed that she was the carrier for the translocation. Her karyotype was 46, XX, t (9;22) (p23; q11.2). Fluorescence in situ hybridisation (FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2 region in the patient, confirming the diagnosis of DiGeorge syndrome. FISH analysis showed no deletion of the region in the mother.

  11. 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.

  12. 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.

  13. Anisotropic thermal transport in double-pancake coil wound with DI-BSCCO® tape

    NASA Astrophysics Data System (ADS)

    Naito, T.; Fujishiro, H.; Yamada, Y.

    2010-11-01

    We have measured the temperature dependence of the thermal resistances Rr(T) and Rz(T) of the parallelepiped samples cut from a double-pancake coil along the radial (r) and the thickness (z) directions, respectively. The double-pancake coil was wound with DI-BSCCO® tape fabricated by Sumitomo Electric Industries, Ltd. DI-BSCCO is a (Bi, Pb)2Sr2Ca2Cu3O10+x tape sheathed with silver. Both Rr(T) and Rz(T) increase monotonically with decreasing temperature. We analyze the thermal transport in the coil by use of the parallel and series heat current circuit of DI-BSCCO tapes and insulators.

  14. 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

  15. 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.

  16. [Experimental verification and prospect on stress effect of Dao-di herbs Scutellaria baicalensis].

    PubMed

    Yuan, Yuan; Zhou, Jun-Hui; Huang, Lu-Qi

    2016-01-01

    The stress effect is a characteristic of Dao-di herbs caused by environmental gene expression of medical plants is influenced by environmental changes and finally affects the formation and accumulation of metabolites. Using Scutellaria baicalensis as material, active component of wild type of S. baicalensis from 19 production areas were analysed; It was found that climate change can influence the accumulation of active components. Then, S. baicalensis suspension cells was exposed to various environments, and enzyme activity and gene expression were measured, indicating the molecular mechanism of stress effect on S. baicalensis. Hence, we found the prerequisite and method to study the stress effect on Dao-di herbs, and we hope this research can provides some references for another studies of Dao-di herbs. Copyright© by the Chinese Pharmaceutical Association.

  17. Retinal vascular tortuosity in DiGeorge syndrome complicated by solar retinopathy.

    PubMed

    De Niro, Jennifer E; Randhawa, Sandeep; McDonald, H Richard

    2013-01-01

    To report a case of vascular tortuosity associated with DiGeorge syndrome that was complicated by solar retinopathy. Case report and literature review. A 56-year-old woman with DiGeorge syndrome with secondary schizophrenia and developmental delay presented with decreased vision that was worse in her left eye. Ocular examination revealed bilateral retinal vascular tortuosity involving both the arteries and veins. Both eyes had an abnormal foveal light reflex with a central yellowish hue, which was more pronounced in the left eye. Optical coherence tomography showed disruption of the photoreceptor inner segment-outer segment junction and retinal pigment epithelium centrally, which was also more prominent in the left eye. DiGeorge syndrome is associated with retinal vascular tortuosity in a large percentage of patients. The patient's decreased vision is likely caused by solar retinopathy (prolonged sun gazing as a result of the secondary schizophrenia and developmental delay).

  18. 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.

  19. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants.

    PubMed

    Ito, Takamitsu; Fujimoto, Shunsuke; Suito, Fumiaki; Shimosaka, Makoto; Taguchi, Goro

    2017-04-02

    Citrus plants accumulate many kinds of flavonoids, including di-C-glucosyl flavonoids, which have attracted considerable attention owing to their health benefits. However, biosynthesis of di-C-glucosyl flavonoids has not been elucidated at the molecular level. Here, we identified the C-glycosyltransferases (CGTs) FcCGT (UGT708G1) and CuCGT (UGT708G2) as the primary enzymes involved in the biosynthesis of di-C-glucosyl flavonoids in the citrus plants kumquat (Fortunella crassifolia) and satsuma mandarin (Citrus unshiu), respectively. The amino acid sequences of these CGTs were 98% identical, indicating that CGT genes are highly conserved in the citrus family. The recombinant enzymes FcCGT and CuCGT utilized 2-hydroxyflavanones, dihydrochalcone, and their mono-C-glucosides as sugar acceptors and produced corresponding di-C-glucosides. The Km and kcat values of FcCGT toward phloretin were <0.5 μM and 12.0 s(-1) , and those toward nothofagin (3'-C-glucosylphloretin) were 14.4 μM and 5.3 s(-1) , respectively; these values are comparable to those of other glycosyltransferases reported to date. Transcripts of both CGT genes were found to concentrate in various plant organs, and particularly in leaves. Our results suggest that di-C-glucosyl flavonoid biosynthesis proceeds via a single enzyme using either 2-hydroxyflavanones or phloretin as a substrate in citrus plants. In addition, Escherichia coli cells expressing CGT genes were found to be capable of producing di-C-glucosyl flavonoids, which is promising for commercial production of these valuable compounds. This article is protected by copyright. All rights reserved.

  20. Biodegradation of diazinon by Serratia marcescens DI101 and its use in bioremediation of contaminated environment.

    PubMed

    Abo-Amer, Aly

    2011-01-01

    Four diazinon-degrading bacteria were isolated from agricultural soil by using an enrichment technique. The biochemical analysis and molecular method including RFLP indicated that these isolates were identical, and one strain designated DI101 was selected for further study. Phylogenetic analysis based on 16S rDNA sequencing indicated that the strain DI101 clearly belongs to the Serratia marcescens group. The ability of the strain to utilize diazinon as a source of carbon and phosphorus was investigated under different culture conditions. The DI101 strain was able to completely degrade 50 mg/l diazinon in MSM within 11 days with a degradation rate of 0.226 day-1. The inoculation of sterilized soil treated with 100 mg/kg of diazinon with 10(6) CFU/g DI101 resulted in a faster degradation rate than was recorded in non-sterilized soil. The diazinon degradation rate by DI101 was efficient at temperatures from 25 to 30degrees C and at pHs from 7.0 to 8.0. The degradation rate of diazinon was not affected by the absence of a phosphorus supplement, and addition of other carbon sources (glucose or succinate) resulted in the slowing down of the degradation rate. The maximum degradation rate (Vmax) of diazinon was 0.292 day-1 and its saturation constant (Ks) was 11 mg/l, as determined by a Michaelis-Menten curve. The strain was able to degrade diethylthiophosphate-containing organophosphates such as chlorpyrifos, coumaphos, parathion, and isazofos when provided as a source of carbon and phosphorus, but not ethoprophos, cadusafos, and fenamiphos. These results propose useful information for the potential application of the DI101 strain in bioremediation of pesticide-contaminated environments.

  1. Constant DI pacing suppresses cardiac alternans formation in numerical cable models

    NASA Astrophysics Data System (ADS)

    Zlochiver, S.; Johnson, C.; Tolkacheva, E. G.

    2017-09-01

    Cardiac repolarization alternans describe the sequential alternation of the action potential duration (APD) and can develop during rapid pacing. In the ventricles, such alternans may rapidly turn into life risking arrhythmias under conditions of spatial heterogeneity. Thus, suppression of alternans by artificial pacing protocols, or alternans control, has been the subject of numerous theoretical, numerical, and experimental studies. Yet, previous attempts that were inspired by chaos control theories were successful only for a short spatial extent (<2 cm) from the pacing electrode. Previously, we demonstrated in a single cell model that pacing with a constant diastolic interval (DI) can suppress the formation of alternans at high rates of activation. We attributed this effect to the elimination of feedback between the pacing cycle length and the last APD, effectively preventing restitution-dependent alternans from developing. Here, we extend this idea into cable models to study the extent by which constant DI pacing can control alternans during wave propagation conditions. Constant DI pacing was applied to ventricular cable models of up to 5 cm, using human kinetics. Our results show that constant DI pacing significantly shifts the onset of both cardiac alternans and conduction blocks to higher pacing rates in comparison to pacing with constant cycle length. We also demonstrate that constant DI pacing reduces the propensity of spatially discordant alternans, a precursor of wavebreaks. We finally found that the protective effect of constant DI pacing is stronger for increased electrotonic coupling along the fiber in the sense that the onset of alternans is further shifted to higher activation rates. Overall, these results support the potential clinical applicability of such type of pacing in improving protocols of implanted pacemakers, in order to reduce the risk of life-threatening arrhythmias. Future research should be conducted in order to experimentally validate

  2. c-di-GMP enhances protective innate immunity in a murine model of pertussis.

    PubMed

    Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A; Gerdts, Volker

    2014-01-01

    Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required.

  3. 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.

  4. 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.

  5. DI2ADEM: an adaptive hypermedia designed to improve access to relevant medical information.

    PubMed

    Pagesy, R; Soula, G; Fieschi, M

    2000-01-01

    The World Wide Web (web) provides the same type of information to widely different users and these users must then find the information suitable for their use in the package offered. The authors present the DI2ADEM project designed to take the user into account and intended to provide this user with appropriate medical information. To do that, DI2ADEM is suggesting an adaptive hypermedia based on the management of a meta-knowledge of the user and a knowledge of the information that can be circulated. An adaptive hypermedia prototype devoted to paediatric oncology was implemented on the intranet network of a university hospital.

  6. A novel rearrangement in ESI-MSn of spirocyclic pentaerythritol di(phosphate monoamides)

    NASA Astrophysics Data System (ADS)

    Ju, Zhi-Yu; Ye, Yong; Zhong, Shang-Bin; Zou, Ru-Yi; Liao, Xin-Cheng; Zhao, Yu-Fen

    2008-06-01

    Several spirocyclic pentaerythritol di(phosphate monoamides) as intumescent flame retardants were synthesized and analyzed by electrospray ionization multistage tandem mass spectrometry. A novel amino group migration from the phosphoryl group to the two methylenes was observed. This migration is believed to be a general pathway for ions with the small size and electronic donating alkyl groups of spirocyclic pentaerythritol di(phosphate monoamides), which is assisted by twice nucleophilic substitutions. Steric and electronic effects of alkyl groups might be a key factor responsible for this migration.

  7. Measurement of q ˆ in Relativistic Heavy Ion Collisions using di-hadron correlations

    NASA Astrophysics Data System (ADS)

    Tannenbaum, M. J.

    2017-08-01

    The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficient q ˆ and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum pT, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle pTt and associated pTa transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, jT, is dominated by kT, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger kT in A+A than in p+p collisions. The present work introduces the observation that the kT measured in p+p collisions for di-hadrons with pTt and pTa must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the kT measured with the same di-hadron pTt and pTa in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result < q ˆ L > = 2.1 ± 0.6 GeV2. This is more precise but in agreement with a theoretical calculation of < q ˆ L > =14-14+42 GeV2 using the same data. Assuming a length < L > ≈ 7 fm for central Au+Au collisions the present result gives q ˆ ≈ 0.30 ± 0.09 GeV2/fm, in fair agreement with the JET collaboration result from single hadron suppression of q ˆ ≈ 1.2 ± 0.3 GeV2/fm at an initial time τ0 = 0.6 fm/c in Au+Au collisions at √{sNN} = 200 GeV.

  8. 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

  9. (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

  10. 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

  11. Migration matrices and surnames in populations with different isolation patterns: Val di Lima (Italian Apennines), Val di Sole (Italian Alps), and La Cabrera (Spain).

    PubMed

    Boattini, Alessio; Calboli, Federico C F; Blanco Villegas, Maria José; Gueresi, Paola; Franceschi, Marcello G; Paoli, Giorgio; Cavicchi, Sandro; Pettener, Davide

    2006-01-01

    Biodemographic methods are widely used to infer the genetic structure of human populations. In this study, we revise and standardize the procedures required by the migration matrix model of Malécot ([1950] Ann Univ Lyon Sci [A] 13:37-60), testing it in large historical-demographic databases of 85 populations from three mountain valleys with different degrees of isolation: Val di Lima (Italian Apennines, 21 parishes), Val di Sole, (Italian Alps, 27 parishes), and La Cabrera (Spain, 37 parishes). An add-on package (Biodem) for the R program is proposed to perform all calculations. Results from migration matrices are compared with those obtained from isonymic relationships. Migration and isonymy matrices are derived from 22,781 marriage records. Matrices are analyzed using a nonlinear isolation-by-distance (IBD) model and multivariate techniques (multidimensional scaling, Procrustes rotation, and cluster analysis). Microdifferentiation levels (F(ST)) from the migration data agree with the observed inbreeding values: higher values are found in La Cabrera (F(ST) = 0.0082), the most isolated population; Val di Lima (F(ST) = 0.0015) and Val di Sole (F(ST) = 0.0012) have lower values due to the larger parish population sizes and greater mobility. Temporal changes of F(ST) and IBD are analyzed using the migration matrix approach. The populations show a marked decline in F(ST) values in time, together with increased population mobility and emigration rates. In all three valleys, marital migration and isonymy yield similar results, suggesting that geographic distance is the most important factor structuring the populations. However, isonymy shows a lower correlation with geographic distance than migration matrices do. This difference can be attributed to the differing sensitivity of the methods for past migration events, and to genetic drift.

  12. [Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin].

    PubMed

    Zhou, Jing; Ma, Hong-yue; Fan, Xin-sheng; Xiao, Wei; Wang, Tuan-jie

    2012-10-01

    To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

  13. 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

    ... 32 National Defense 4 2012-07-01 2011-07-01 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...

  14. 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

    ... 32 National Defense 4 2014-07-01 2013-07-01 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...

  15. 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

    ... 32 National Defense 4 2013-07-01 2013-07-01 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...

  16. 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…

  17. 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...

  18. Brucella melitensis Cyclic di-GMP Phosphodiesterase BpdA Controls Expression of Flagellar Genes▿†

    PubMed Central

    Petersen, Erik; Chaudhuri, Pallab; Gourley, Chris; Harms, Jerome; Splitter, Gary

    2011-01-01

    Brucella melitensis encounters a variety of conditions and stimuli during its life cycle—including environmental growth, intracellular infection, and extracellular dissemination—which necessitates flexibility of bacterial signaling to promote virulence. Cyclic-di-GMP is a bacterial secondary signaling molecule that plays an important role in adaptation to changing environments and altering virulence in a number of bacteria. To investigate the role of cyclic-di-GMP in B. melitensis, all 11 predicted cyclic-di-GMP-metabolizing proteins were separately deleted and the effect on virulence was determined. Three of these cyclic-di-GMP-metabolizing proteins were found to alter virulence. Deletion of the bpdA and bpdB genes resulted in attenuation of virulence of the bacterium, while deletion of the cgsB gene produced a hypervirulent strain. In a Vibrio reporter system to monitor apparent alteration in levels of cyclic-di-GMP, both BpdA and BpdB displayed a phenotype consistent with cyclic-di-GMP-specific phosphodiesterases, while CgsB displayed a cyclic-di-GMP synthase phenotype. Further analysis found that deletion of bpdA resulted in a dramatic decrease in flagellar promoter activities, and a flagellar mutant showed similar phenotypes to the bpdA and bpdB mutant strains in mouse models of infection. These data indicate a potential role for regulation of flagella in Brucella melitensis via cyclic-di-GMP. PMID:21856843

  19. 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...

  20. 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...

  1. 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....

  2. 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....

  3. 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...

  4. Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm.

    PubMed

    Huynh, TuAnh Ngoc; Woodward, Joshua J

    2016-04-01

    Bacteria that synthesize c-di-AMP also encode several mechanisms for controlling c-di-AMP levels within the cytoplasm. One major class of phosphodiesterases comprises GdpP and DhhP homologs, which degrade c-di-AMP into the linear molecule 5'-pApA or AMP by the DHH-DHHA1 domain. The other major class comprises PgpH homologs, which degrade c-di-AMP by the HD domain. Both GdpP and PgpH harbor sensory domains, likely to regulate c-di-AMP hydrolysis activity in response to signal input. As another possible mechanism for controlling cytoplasmic c-di-AMP levels, bacteria also secrete c-di-AMP via multidrug resistance transporters, as demonstrated for Listeria monocytogenes. Mutants that accumulate high c-di-AMP levels, by deletion of phosphodiesterases or multidrug resistance transporters, exhibit aberrant physiology, growth defects, and attenuated virulence in infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation.

    PubMed

    Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo; Berthelsen, Jens; Liu, Yang; Yang, Liang; Nielsen, Thomas E; Kaever, Volkhard; Givskov, Michael; Tolker-Nielsen, Tim

    2016-10-01

    Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP content in P. aeruginosa, doxorubicin was unable to inhibit biofilm formation or disperse established biofilms. On the contrary, the drug was found to promote P. aeruginosa biofilm formation, possibly through release of extracellular DNA from a subpopulation of killed bacteria. Our findings emphasize that lowering of the c-di-GMP content in bacteria might not be sufficient to mediate biofilm inhibition or dispersal.

  6. 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...

  7. 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...

  8. 76 FR 51980 - Atlantic Shipping Company, Inc. v. Di Nos Shipping, Inc.; Notice of Filing of Complaint and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... COMMISSION Atlantic Shipping Company, Inc. v. Di Nos Shipping, Inc.; Notice of Filing of Complaint and...) by Atlantic Shipping Company, Inc., hereinafter ``Complainant,'' against DI Nos Shipping, Inc... Respondent is in violation of the Shipping Act of 1984, 46 U.S.C. 40901 and 40902, by operating as a freight...

  9. 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…

  10. Cyclic-di-GMP binding induces structural rearrangements in the PlzA and PlzC proteins of the Lyme disease and relapsing fever spirochetes: a possible switch mechanism for c-di-GMP-mediated effector functions.

    PubMed

    Mallory, Katherine L; Miller, Daniel P; Oliver, Lee D; Freedman, John C; Kostick-Dunn, Jessica L; Carlyon, Jason A; Marion, James D; Bell, Jessica K; Marconi, Richard T

    2016-11-01

    The c-di-GMP network of Borrelia burgdorferi, a causative agent of Lyme disease, consists of Rrp1, a diguanylate cyclase/response regulator; Hpk1, a histidine kinase; PdeA and PdeB, c-di-GMP phosphodiesterases; and PlzA, a PilZ domain c-di-GMP receptor. Borrelia hermsii, a causative agent of tick-borne relapsing fever, possesses a putative c-di-GMP regulatory network that is uncharacterized. While B. burgdorferi requires c-di-GMP to survive within ticks, the associated effector mechanisms are poorly defined. Using site-directed mutagenesis, size exclusion chromatography, isothermal titration calorimetry and fluorescence resonance energy transfer, we investigate the interaction of c-di-GMP with the Borrelia PilZ domain-containing Plz proteins: B. burgdorferi PlzA and B. hermsii PlzC. The Plz proteins were determined to be monomeric in their apo and holo forms and to bind c-di-GMP with high affinity with a 1:1 stoichiometry. C-di-GMP binding induced structural rearrangements in PlzA and PlzC. C-di-GMP binding proved to be dependent on positive charge at R145 of the PilZ domain motif, R145xxxR. Comparative sequence analyses led to the identification of Borrelia consensus sequences for the PilZ domain signature motifs. This study provides insight into c-di-GMP:Plz receptor interaction and identifies a possible switch mechanism that may regulate Plz protein effector functions. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2016-05-01

    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 diagnosis. Confirmatory factor analyses found a better fit against a DSM-5 model than a DSM-IV-TR model of ASD. Exploration of the content validity of the 3Di-sv for the DSM-5 revealed some construct underrepresentation, therefore we obtained data from a panel of 3Di-trained clinicians from ASD-specialized centers to recommend items to fill these gaps. Taken together, the 3Di-sv provides a solid basis to create a similar instrument suitable for DSM-5. Concrete recommendations are provided to improve DSM-5 compatibility.

  12. c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria.

    PubMed

    Fahmi, Tazin; Port, Gary C; Cho, Kyu Hong

    2017-08-07

    Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an

  13. 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.

  14. c-di-GMP can form remarkably stable G-quadruplexes at physiological conditions in the presence of some planar intercalators.

    PubMed

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

    2011-04-28

    The ubiquitous bacterial biofilm regulator, c-di-GMP can form G-quadruplexes at physiological conditions in the presence of some aromatic compounds, such as acriflavine and proflavine. The fluorescence of these compounds is quenched upon c-di-GMP binding and some of the formed c-di-GMP G-quadruplexes are stable even at 75 °C.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Method of dissolving metal oxides with di- or polyphosphonic acid and a redundant

    DOEpatents

    Horwitz, Earl P.; Chiarizia, Renato

    1996-01-01

    A method of dissolving metal oxides using a mixture of a di- or polyphosphonic acid and a reductant wherein each is present in a sufficient amount to provide a synergistic effect with respect to the dissolution of metal oxides and optionally containing corrosion inhibitors and pH adjusting agents.

  17. Draft Genome Sequence of the Xylella fastidiosa CoDiRO Strain

    PubMed Central

    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

  18. Difference gel electrophoresis (DiGE) identifies differentially expressed proteins in endoscopically-collected pancreatic fluid

    PubMed Central

    Paulo, Joao A.; Lee, Linda S.; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

    2012-01-01

    Alterations in the pancreatic fluid proteome of individuals with chronic pancreatitis may offer insights into the development and progression of the disease. The endoscopic pancreas function test (ePFT) can safely collect large volumes of pancreatic fluid that are potentially amenable to proteomic analyses using difference gel electrophoresis (DiGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pancreatic fluid was collected endoscopically using the ePFT method following secretin stimulation from three individuals with severe chronic pancreatitis and three chronic abdominal pain controls. The fluid was processed to minimize protein degradation and the protein profiles of each cohort, as determined by DiGE and LC-MS/MS, were compared. This DiGE-LC-MS/MS analysis reveals proteins that are differentially expressed in chronic pancreatitis compared to chronic abdominal pain controls. Proteins with higher abundance in pancreatic fluid from chronic pancreatitis individuals include: actin, desmoplankin, alpha-1-antitrypsin, SNC73, and serotransferrin. Those of relatively lower abundance include carboxypeptidase B, lipase, alpha-1-antichymotrypsin, alpha-2-macroglobulin, Arp2/3 subunit 4, glyceraldehyde-3-phosphate dehydrogenase, and protein disulfide isomerase. Endoscopic collection (ePFT) in tandem with DiGE-LC-MS/MS is a suitable approach for pancreatic fluid proteome analysis, however, further optimization of our protocol, as outlined herein, may improve proteome coverage in future analyses. PMID:21792986

  19. MONO-(3-CARBOXYPROPYL) PHTHALATE, A METABOLITE OF DI-N-OCTYL PHTHALATE

    EPA Science Inventory

    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, mo...

  20. 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...

  1. Partial attenuation of Marek's disease virus by manipulation of Di-codon bias

    USDA-ARS?s Scientific Manuscript database

    All species studied to date demonstrate a preference for certain codons over other synonymous codons (codon bias), a preference which is also observed for pairs of codons (di-codon bias). Previous studies using poliovirus and influenza virus as models have demonstrated the ability to cause attenuat...

  2. 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...

  3. 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

  4. Synthesis and comparative anion binding profiles of two di-aqua Eu(III) complexes.

    PubMed

    Imperio, Daniela; Giovenzana, Giovanni B; Law, Ga-Lai; Parker, David; Walton, James W

    2010-11-07

    Two di-aqua Eu(iii) complexes of heptadentate ligands are reported that show differing reactivity profiles towards various anions; a cationic complex with two azaxanthone moieties exhibits pronounced selectivity towards bicarbonate with an affinity constant, logK = 2.65 (295 K, 0.1 M NaCl).

  5. 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...

  6. 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.

  7. 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...

  8. Shallow subsurface drip irrigation (S3DI) for small irregular-shaped fields in the southeast

    USDA-ARS?s Scientific Manuscript database

    Field tests were conducted using S3DI on cotton (Gossypium hirsutum, L.), corn (Zea mays, L.), and peanut (Arachis hypogeae, L.) rotations to investigate yield potential and economic sustainability of this irrigation system. Drip tubing was installed in alternate row middles, strip tillage was used ...

  9. Yield and economics of shallow subsurface drip irrigation (S3DI) and furrow diking

    USDA-ARS?s Scientific Manuscript database

    A shallow subsurface drip irrigation (S3DI) was installed yearly in conjunction with furrow diking to document yield and economic benefit of these techniques on peanut (Arachis hypogaea L.), cotton (Gossypium hirsutum L.), and corn (Zea mays L.). This research was conducted for three years from 2005...

  10. 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

  11. 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…

  12. 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...

  13. Elastic Constants of Rare Earth and Transition Metal Di-Hydrides

    NASA Astrophysics Data System (ADS)

    Snow, C. S.; Knapp, J. A.; Browning, J. F.

    2007-03-01

    Determinations of the elastic constants of rare earth (RE=Er, La,) and some transition metal (TM=Sc, Ti, Zr) di-hydrides are extremely difficult. Single crystals of these di-hydrided metals can not be obtained because they break up into fine powders due to the large stresses in the materials caused by the crystallographic changes upon hydriding. However, polycrystalline thin films of these hydrided materials can be grown and are stable over a wide temperature and pressure range. In order to determine the elastic constants of thin metal di-hydride films ab-initio electronic structure calculations using the VASP code have been carried out. These calculations are then compared to bulk and shear moduli measured by a nano-indentation technique. Details and results of the calculations and measurements of the elastic constants of rare earth and transition metal di-hydride films will be presented and a discussion of future applications of this technique will be given.

  14. 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. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. 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

  16. 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 ...

  17. The Instructional Instrument SL-EDGE Student Library-Educational DiGital Environment.

    ERIC Educational Resources Information Center

    Kyriakopoulou, Antonia; Kalamboukis, Theodore

    An educational digital environment that will provide appropriate methods and techniques for the support and enhancement of the educational and learning process is a valuable tool for both educators and learners. In the context of such a mission, the educational tool SL-EDGE (Student Library-Educational DiGital Environment) has been developed. The…

  18. 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…

  19. Deoxythymidine 3', 5'-di-p-nitrophenyl phosphate as a synthetic substrate for bovine pancreatic deoxyribonuclease.

    PubMed

    Liao, T

    1975-05-25

    Bovine pancreatic deoxyribonuclease liberates p-nitrophenol from the 3'-group of deoxythymidine 3', 5'-di-p-nitrophenyl phosphate. A similar hydrolysis occurs with deoxythymidine 3'-p-nitrophenyl phosphate 5'-phsophate, but the rate is less than 2% of that with the di-p-nitrophenyl ester. The rate of formation of the p-nitrophenol, measured spectrophotometrically at 400 nm, varies linearly with DNase concentration. The binding of the substrate is not strong (K-m(app) in the 10 mM range), but the hydrolysis is rapid; 1 mug of DNase (free from other phosphodiesterases) can be assayed in 3 min after addition to a 10 mM substrate solution at pH 7.2, 10mM in MnCl2, and 1mM in CaCl2. All four bovine pancreatic DNases (A,B,C, and D) show the same relative activities toward DNA and toward the di-p-nitrophenyl ester; both activities are lost when DNase is inactivated by iodoacetate or by trypsin. The specificity of DNase toward the di-p-nitrophenyl substrate is different from that which has been established for the enzyme's predominant action on DNA or synthetic oligonucleotides, where a monoesterified phosphate group is formed at the 5'-position.

  20. 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...

  1. Three new di-O-glycosyl-C-glucosyl flavones from the leaves of Caesalpinia ferrea Mart..

    PubMed

    Nawwar, Mahmoud; El-Mousallami, Amani; Hussein, Sahar; Hashem, Amani; Mousa, Mona; Lindequist, Ulrike; Linscheid, Michael

    2014-01-01

    Three hitherto unknown di-O-xylosyl-C-glycosyl flavones were isolated from the leaves of Caesalpinia ferrea. The structures of all isolated compounds were elucidated by conventional methods and spectroscopic analysis, including 1D and 2D NMR, as well as by HRESIMS.

  2. MALDI-TOF Mass Spectrometry of Naturally-Occurring Mixtures of Mono- and Di-rhamnolipids

    USDA-ARS?s Scientific Manuscript database

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been developed for high-throughput screening of naturally-occurring mixtures of rhamnolipids from Pseudomonas spp. Mono- and di-rhamnolipids are readily distinguished by characteristic molecular adduct i...

  3. MONO-(3-CARBOXYPROPYL) PHTHALATE, A METABOLITE OF DI-N-OCTYL PHTHALATE

    EPA Science Inventory

    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, mo...

  4. 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...

  5. 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 ...

  6. Cyclic Di-GMP Signaling Contributes to Pseudomonas aeruginosa-Mediated Catheter-Associated Urinary Tract Infection

    PubMed Central

    Cole, Stephanie J.

    2015-01-01

    ABSTRACT Bis-(3′-5′) cyclic dimeric GMP (c-di-GMP) controls the lifestyle transition between the sessile and motile states in many Gram-negative bacteria, including the opportunistic human pathogen Pseudomonas aeruginosa. Under laboratory conditions, high concentrations of c-di-GMP decrease motility and promote biofilm formation, while low concentrations of c-di-GMP promote motility and decease biofilm formation. Here we sought to determine the contribution of c-di-GMP signaling to biofilm formation during P. aeruginosa-mediated catheter-associated urinary tract infection (CAUTI). Using a murine CAUTI model, a decrease in CFU was detected in the bladders and kidneys of mice infected with strains overexpressing the phosphodiesterases (PDEs) encoded by PA3947 and PA2133 compared to those infected with wild-type P. aeruginosa. Conversely, overexpression of the diguanylate cyclases (DGCs) encoded by PA3702 and PA1107 increased the number of bacteria in bladder and significantly increased dissemination of bacteria to the kidneys compared to wild-type infection. To determine which of the DGCs and PDEs contribute to c-di-GMP signaling during infection, a panel of PA14 in-frame deletion mutants lacking DGCs and PDEs were tested in the CAUTI model. Results from these infections revealed five mutants, three containing GGDEF domains (ΔPA14_26970, ΔPA14_72420, and ΔsiaD) and two containing dual GGDEF-EAL domains (ΔmorA and ΔPA14_07500), with decreased colonization of the bladder and dissemination to the kidneys. These results indicate that c-di-GMP signaling influences P. aeruginosa-mediated biofilms during CAUTI. IMPORTANCE Biofilm-based infections are an important cause of nosocomial infections, since they resist the immune response and traditional antibiotic treatment. Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in many Gram-negative pathogens, including Pseudomonas aeruginosa. Here we determined the contribution of c-di

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

    DOE PAGES

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.; ...

    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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Analysis of tomographic mineralogical data using YaDiV—Overview and practical case study

    NASA Astrophysics Data System (ADS)

    Friese, Karl-Ingo; Cichy, Sarah B.; Wolter, Franz-Erich; Botcharnikov, Roman E.

    2013-07-01

    We introduce the 3D-segmentation and -visualization software YaDiV to the mineralogical application of rock texture analysis. YaDiV has been originally designed to process medical DICOM datasets. But due to software advancements and additional plugins, this open-source software can now be easily used for the fast quantitative morphological characterization of geological objects from tomographic datasets. In this paper, we give a summary of YaDiV's features and demonstrate the advantages of 3D-stereographic visualization and the accuracy of 3D-segmentation for the analysis of geological samples. For this purpose, we present a virtual and a real use case (here: experimentally crystallized and vesiculated magmatic rocks, corresponding to the composition of the 1991-1995 Unzen eruption, Japan). Especially the spacial representation of structures in YaDiV allows an immediate, intuitive understanding of the 3D-structures, which may not become clear by only looking on 2D-images. We compare our results of object number density calculations with the established classical stereological 3D-correction methods for 2D-images and show that it was possible to achieve a seriously higher quality and accuracy. The methods described in this paper are not dependent on the nature of the object. The fact, that YaDiV is open-source and users with programming skills can create new plugins themselves, may allow this platform to become applicable to a variety of geological scenarios from the analysis of textures in tiny rock samples to the interpretation of global geophysical data, as long as the data are provided in tomographic form.

  13. Cyclic Di-GMP-Regulated Periplasmic Proteolysis of a Pseudomonas aeruginosa Type Vb Secretion System Substrate.

    PubMed

    Cooley, Richard B; Smith, T Jarrod; Leung, Wilfred; Tierney, Valerie; Borlee, Bradley R; O'Toole, George A; Sondermann, Holger

    2015-06-22

    We previously identified a second-messenger-regulated signaling system in the environmental bacterium Pseudomonas fluorescens which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse bacteria, predictions of LapG substrates are sparse. Notably, the opportunistic pathogen Pseudomonas aeruginosa harbors LapDG orthologs, but neither the substrate of LapG nor any associated secretion machinery has been identified to date. Here, we identified P. aeruginosa CdrA, a protein known to mediate cell-cell aggregation and biofilm maturation, as a substrate of LapG. We also demonstrated LapDG to be a minimal system sufficient to control CdrA localization in response to changes in the intracellular concentration of c-di-GMP. Our work establishes this biofilm signaling node as a regulator of a type Vb secretion system substrate in a clinically important pathogen. Here, the biological relevance of a conserved yet orphan signaling system in the opportunistic pathogen Pseudomonas aeruginosa is revealed. In particular, we identified the adhesin CdrA, the cargo of a two-partner secretion system, as a substrate of a periplasmic protease whose activity is controlled by intracellular c-di-GMP levels and a corresponding transmembrane receptor via an inside-out signaling mechanism. The data indicate a posttranslational control mechanism of CdrA via c-di-GMP, in addition to its established transcriptional regulation via the same second messenger. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Cyclic Di-GMP-Regulated Periplasmic Proteolysis of a Pseudomonas aeruginosa Type Vb Secretion System Substrate

    PubMed Central

    Cooley, Richard B.; Smith, T. Jarrod; Leung, Wilfred; Tierney, Valerie; Borlee, Bradley R.; O'Toole, George A.

    2015-01-01

    ABSTRACT We previously identified a second-messenger-regulated signaling system in the environmental bacterium Pseudomonas fluorescens which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse bacteria, predictions of LapG substrates are sparse. Notably, the opportunistic pathogen Pseudomonas aeruginosa harbors LapDG orthologs, but neither the substrate of LapG nor any associated secretion machinery has been identified to date. Here, we identified P. aeruginosa CdrA, a protein known to mediate cell-cell aggregation and biofilm maturation, as a substrate of LapG. We also demonstrated LapDG to be a minimal system sufficient to control CdrA localization in response to changes in the intracellular concentration of c-di-GMP. Our work establishes this biofilm signaling node as a regulator of a type Vb secretion system substrate in a clinically important pathogen. IMPORTANCE Here, the biological relevance of a conserved yet orphan signaling system in the opportunistic pathogen Pseudomonas aeruginosa is revealed. In particular, we identified the adhesin CdrA, the cargo of a two-partner secretion system, as a substrate of a periplasmic protease whose activity is controlled by intracellular c-di-GMP levels and a corresponding transmembrane receptor via an inside-out signaling mechanism. The data indicate a posttranslational control mechanism of CdrA via c-di-GMP, in addition to its established transcriptional regulation via the same second messenger. PMID:26100041

  15. 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.

    2015-01-01

    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 work, 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. Finally, 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.

  16. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-09-28

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  17. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-09-28

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The visual shows Hurricane Sandy. The visual uses data from Goddard Earth Observing System Model, Version 5 (GEOS-5) to simulate surface wind speeds across the Atlantic during Sandy’s lifecycle. svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=30465 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  18. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-09-28

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The background visual shows the biosphere with data from a NASA satellite instrument called the Sea-viewing Wide Field-of-View Sensor (SeaWiFS). svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=10704 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  19. Stimulatory actions of di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS), voltage-sensitive dye, on the BKCa channel in pituitary tumor (GH3) cells.

    PubMed

    Wu, Sheng-Nan; Lin, Ming-Wei; Wang, Ya-Jean

    2008-01-01

    Di-8-ANEPPS (4-{2-[6-(dibutylamino)-2-naphthalenyl]-ethenyl}-1-(3-sulfopropyl)pyridinium inner salt) has been used as a fast-response voltage-sensitive styrylpyridinium probe. However, little is known regarding the mechanism of di-8-ANEPPS actions on ion currents. In this study, the effects of this dye on ion currents were investigated in pituitary GH(3) cells. In whole-cell configuration, di-8-ANEPPS (10 microM) reversibly increased the amplitude of Ca(2+)-activated K(+) current. In inside-out configuration, di-8-ANEPPS (10 microM) applied to the intracellular surface of the membrane caused no change in single-channel conductance; however, it did enhance the activity of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels with an EC(50) value of 7.5 microM. This compound caused a left shift in the activation curve of BK(Ca) channels with no change in the gating charge of these channels. A decrease in mean closed time of the channels was seen in the presence of this dye. In the cell-attached mode, di-8-ANEPPS applied on the extracellular side of the membrane also activated BK(Ca) channels. However, neither voltage-gated K(+) nor ether-à-go-go-related gene (erg)-mediated K(+) currents in GH(3) cells were affected by di-8-APPNES. Under current-clamp configuration, di-8-ANEPPS (10 microM) decreased the firing of action potentials in GH(3) cells. In pancreatic betaTC-6 cells, di-8-APPNES (10 microM) also increased BK(Ca)-channel activity. Taken together, this study suggests that during the exposure to di-8-ANEPPS, the stimulatory effects on BK(Ca) channels could be one of potential mechanisms through which it may affect cell excitability.

  20. 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.

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

    DOE PAGES

    Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.; ...

    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

  2. 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.

  3. Protection of hepatocytes against death due to mitochondrial failure: effect of di-Calciphor on antimycin A-induced toxicity.

    PubMed

    Park, Y; Devlin, T M; Jones, D P

    1994-05-01

    Di-Calciphor is a synthetic derivative of prostaglandin B1 that protects against cerebral and cardiac ischemia apparently by preserving mitochondrial function. To determine whether di-Calciphor specifically protects against mitochondrial failure, we studied its effects on mitochondrial functions in hepatocytes treated with the specific mitochondrial poison, antimycin A. The results show that 1 microM di-Calciphor protects against cell death at concentrations of antimycin A that inhibited mitochondrial respiration and caused cellular ATP depletion. Di-Calciphor did not protect against loss of ATP but did protect against the loss of mitochondrial delta psi and delta pH. In addition, di-Calciphor protected against antimycin A-induced loading of phosphate into mitochondria and an associated mitochondrial swelling. Thus, these results show that di-Calciphor protects against a specific mitochondrial poison and support the interpretation that di-Calciphor is a mitochondrial protective agent. In addition, the results suggest that the protection of the mitochondria involves preservation of mitochondrial ionic and osmotic stability and does not involve improved ATP supply.

  4. The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus

    PubMed Central

    Tosi, Tommaso; Campeotto, Ivan; Corrigan, Rebecca M.; Freemont, Paul; Gründling, Angelika

    2017-01-01

    Staphylococcus aureus is an important opportunistic human pathogen that is highly resistant to osmotic stresses. In order to survive an increase in osmolarity, bacteria immediately take up potassium and small organic compounds, also referred to as compatible solutes. The second messenger c-di-AMP binds to several receptor proteins, most of which are involved in ion and potassium uptake, that help bacteria cope with osmotic stress. In this study, we identified OpuCA, the ATPase component of an uptake system for the compatible solute carnitine, as a c-di-AMP target protein in S. aureus and found that a strain overproducing c-di-AMP showed reduced carnitine uptake. The CBS domains of OpuCA bound to c-di-AMP, and a crystal structure revealed a putative binding pocket for c-di-AMP in the cleft between the two CBS domains. Thus, c-di-AMP is involved in regulating both branches of osmoprotection (potassium uptake and compatible solute uptake), suggesting that c-di-AMP is a general osmotic stress regulator. PMID:27531650

  5. 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

  6. Structural and biochemical characterization of linear dinucleotide analogs bound to the c-di-GMP-I aptamer†,‡

    PubMed Central

    Smith, Kathryn D.; Lipchock, Sarah V.; Strobel, Scott A.

    2011-01-01

    The cyclic dinucleotide c-di-GMP regulates lifestyle transitions in many bacteria, such as the change from a free motile state to a biofilm-forming community. Riboswitches that bind this second messenger are important downstream targets in this bacterial signaling pathway. The breakdown of c-di-GMP in the cell is accomplished enzymatically and results in the linear dinucleotide pGpG. The c-di-GMP-binding riboswitches must be able to discriminate between their cognate cyclic ligand and linear dinucleotides in order to be selective biological switches. It has been reported that the cdi-GMP-I riboswitch binds c-di-GMP five orders of magnitude better than the linear pGpG, but the cause of this large energetic difference in binding is unknown. Here we report binding data and crystal structures of several linear c-di-GMP analogs in complex with the c-di-GMP-I riboswitch. These data reveal the parameters for phosphate recognition and the structural basis of linear dinucleotide binding to the riboswitch. Additionally, the pH dependence of binding shows that exclusion of pGpG is not due to the additional negative charge on the ligand. These data reveal principles that, along with published work, will contribute to the design of c-di-GMP analogs with properties desirable for use as chemical tools and potential therapeutics. PMID:22148472

  7. Cohesive Properties of the Caulobacter crescentus Holdfast Adhesin Are Regulated by a Novel c-di-GMP Effector Protein

    PubMed Central

    Sprecher, Kathrin S.; Hug, Isabelle; Nesper, Jutta; Potthoff, Eva; Mahi, Mohamed-Ali; Sangermani, Matteo; Kaever, Volkhard; Schwede, Torsten; Vorholt, Julia

    2017-01-01

    ABSTRACT When encountering surfaces, many bacteria produce adhesins to facilitate their initial attachment and to irreversibly glue themselves to the solid substrate. A central molecule regulating the processes of this motile-sessile transition is the second messenger c-di-GMP, which stimulates the production of a variety of exopolysaccharide adhesins in different bacterial model organisms. In Caulobacter crescentus, c-di-GMP regulates the synthesis of the polar holdfast adhesin during the cell cycle, yet the molecular and cellular details of this control are currently unknown. Here we identify HfsK, a member of a versatile N-acetyltransferase family, as a novel c-di-GMP effector involved in holdfast biogenesis. Cells lacking HfsK form highly malleable holdfast structures with reduced adhesive strength that cannot support surface colonization. We present indirect evidence that HfsK modifies the polysaccharide component of holdfast to buttress its cohesive properties. HfsK is a soluble protein but associates with the cell membrane during most of the cell cycle. Coincident with peak c-di-GMP levels during the C. crescentus cell cycle, HfsK relocalizes to the cytosol in a c-di-GMP-dependent manner. Our results indicate that this c-di-GMP-mediated dynamic positioning controls HfsK activity, leading to its inactivation at high c-di-GMP levels. A short C-terminal extension is essential for the membrane association, c-di-GMP binding, and activity of HfsK. We propose a model in which c-di-GMP binding leads to the dispersal and inactivation of HfsK as part of holdfast biogenesis progression. PMID:28325767

  8. 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

  9. 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

  10. 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

  11. DiPyMe in SDS Micelles: Artifacts and Their Implications in the Interpretation of Micellar Properties.

    PubMed

    Fowler, Michael; Hisko, Victoria; Henderson, Jason; Casier, Remi; Li, Lu; Thoma, Janine Lydia; Duhamel, Jean

    2015-11-10

    This study provides experimental evidence that di(1-pyrenylmethyl) ether or DiPyMe, a well-known fluorescent probe employed to determine the microviscosity of surfactant or polymeric micelles, is being hydrolyzed in the presence of water upon UV irradiation. This effect was established from a careful analysis of the fluorescence spectra and decays acquired with aqueous solutions of DiPyMe dissolved in micelles of sodium dodecyl sulfate (SDS). The size of the SDS micelles could be adjusted from an aggregation number (N(agg)) of 70 to 172 by increasing the ionic strength of the aqueous solution from 0.0 to 0.5 M NaCl. The hydrolysis of DiPyMe was much reduced in the larger SDS micelles. While the degradation of DiPyMe in aqueous solutions of SDS micelles affected the analysis of the fluorescence spectra, model-free analysis (MFA) of the fluorescence decays of DiPyMe could reliably retrieve the rate constant ⟨k⟩ of excimer formation for DiPyMe. After calibration with mixtures of organic solvents of known macroscopic viscosity, the ⟨k⟩ values obtained for DiPyMe yielded the microviscosity (μη) of the SDS micelles as a function of salt concentration. The μη was found to increase from 4.0 to 8.8 mPa·s as the salt concentration increased from 0.0 to 0.5 M. This study demonstrated that, regardless of the problem of its hydrolysis that jeopardizes its use in steady-state fluorescence experiments, DiPyMe remains an extremely valuable probe for describing the microviscosity of hydrophobic domains in aqueous solution as long as its decays are analyzed with a model that accounts for the presence of degradation products as the MFA does.

  12. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    PubMed Central

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  13. 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.

  14. Structural Insights into the Distinct Binding Mode of Cyclic Di-AMP with SaCpaA_RCK.

    PubMed

    Chin, Ko-Hsin; Liang, Juin-Ming; Yang, Jauo-Guey; Shih, Min-Shao; Tu, Zhi-Le; Wang, Yu-Chuang; Sun, Xing-Han; Hu, Nien-Jen; Liang, Zhao-Xun; Dow, J Maxwell; Ryan, Robert P; Chou, Shan-Ho

    2015-08-11

    Cyclic di-AMP (c-di-AMP) is a relatively new member of the family of bacterial cyclic dinucleotide second messengers. It has attracted significant attention in recent years because of the abundant roles it plays in a variety of Gram-positive bacteria. The structural features that allow diverse bacterial proteins to bind c-di-AMP are not fully understood. Here we report the biophysical and structural studies of c-di-AMP in complex with a bacterial cation-proton antiporter (CpaA) RCK (regulator of the conductance of K(+)) protein from Staphylococcus aureus (Sa). The crystal structure of the SaCpaA_RCK C-terminal domain (CTD) in complex with c-di-AMP was determined to a resolution of 1.81 Å. This structure revealed two well-liganded water molecules, each interacting with one of the adenine bases by a unique H2Olp-π interaction to stabilize the complex. Sequence blasting using the SaCpaA_RCK primary sequence against the bacterial genome database returned many CpaA analogues, and alignment of these sequences revealed that the active site residues are all well-conserved, indicating a universal c-di-AMP binding mode for CpaA_RCK. A proteoliposome activity assay using the full-length SaCpaA membrane protein indicated that c-di-AMP binding alters its antiporter activity by approximately 40%. A comparison of this structure to all other reported c-di-AMP-receptor complex structures revealed that c-di-AMP binds to receptors in either a "U-shape" or "V-shape" mode. The two adenine rings are stabilized in the inner interaction zone by a variety of CH-π, cation-π, backbone-π, or H2Olp-π interaction, but more commonly in the outer interaction zone by hydrophobic CH-π or π-π interaction. The structures determined to date provide an understanding of the mechanisms by which a single c-di-AMP can interact with a variety of receptor proteins, and how c-di-AMP binds receptor proteins in a special way different from that of c-di-GMP.

  15. Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci

    PubMed Central

    2011-01-01

    Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences. Methods We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS. The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis. Results We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome. Conclusion Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling. PMID:21406098

  16. Crystal structure of [N,N′-bis­(4-methyl­phen­yl)-1,2-di­phenyl­ethane-1,2-di­imine-κ2 N,N′]di­chlorido­palladium(II) methanol monosolvate

    PubMed Central

    Peñaloza, Alfredo; Fronczek, Frank R.; Isovitsch, Ralph

    2015-01-01

    The title compound, [PdCl2(C28H24N2)]·CH3OH, was pre­pared from the reaction of PdCl2(DMSO)2 (DMSO is di­methyl sulfoxide) and N,N′-bis­(4-methyl­phen­yl)-1,2-di­phenyl­ethane-1,2-di­imine in methanol. The chelating di­imine core of the title compound deviates slightly from planarity, with an N—C—C—N torsion angle of 5.3 (3)°. Delocalization in the di­imine core is indicated by N—C and C—C bonds that are, respectively, longer and shorter than those found in related nonchelating di­imines. The distorted square-planar coordination environment around the PdII atom is manifested as bond angles that are smaller and larger than 90°, and palladacycle torsion angles of −173.22 (16) and 167.06 (16)°. These deviations are attributed to the small bite angle of 79.13 (8)° of the di­imine chelate. The crystal packing exhibits weak inter­molecular hydrogen-bonding inter­actions involving aromatic H atoms, Cl atoms and inter­calated methanol solvent mol­ecules, defining layers parallel to (010). PMID:26396867

  17. 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

  18. 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 Central

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

    2015-01-01

    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. PMID:25957408

  19. 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.

  20. Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

    PubMed Central

    He, Ming; Ouyang, Zhiming; Troxell, Bryan; Xu, Haijun; Moh, Akira; Piesman, Joseph; Norgard, Michael V.; Gomelsky, Mark; Yang, X. Frank

    2011-01-01

    Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host. PMID:21738477

  1. 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.

  2. 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

  3. 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

  4. Genetic Modulation of c-di-GMP Turnover Affects Multiple Virulence Traits and Bacterial Virulence in Rice Pathogen Dickeya zeae

    PubMed Central

    Chen, Yufan; Lv, Mingfa; Liao, Lisheng; Gu, Yanfang; Liang, Zhibin; Shi, Zurong; Liu, Shiyin; Zhou, Jianuan; Zhang, Lianhui

    2016-01-01

    The frequent outbreaks of rice foot rot disease caused by Dickeya zeae have become a significant concern in rice planting regions and countries, but the regulatory mechanisms that govern the virulence of this important pathogen remain vague. Given that the second messenger cyclic di-GMP (c-di-GMP) is associated with modulation of various virulence-related traits in various microorganisms, here we set to investigate the role of the genes encoding c-di-GMP metabolism in the regulation of the bacterial physiology and virulence by construction all in-frame deletion mutants targeting the annotated c-di-GMP turnover genes in D. zeae strain EC1. Phenotype analyses identified individual mutants showing altered production of exoenzymes and phytotoxins, biofilm formation and bacterial motilities. The results provide useful clues and a valuable toolkit for further characterization and dissection of the regulatory complex that modulates the pathogenesis and persistence of this important bacterial pathogen. PMID:27855163

  5. 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.

  6. 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.

  7. Extreme-Mg olivines from venancite lavas of Pian di Celle volcano (Italy)

    NASA Astrophysics Data System (ADS)

    Plechov, P. Yu.; Nekrylov, N. A.; Shcherbakov, V. D.; Tikhonova, M. S.

    2017-05-01

    Olivines with a forsterite minal of up to 99.5 mol % were discovered in ultra-potassium lavas of Pian di Celle volcano (Italy). Based on high-precision analyses of these olivines and the available literature data, a new type of extreme-Mg olivines with a forsterite content of >96 mol % was distinguished. These olivines could have formed as a result of oxidation of lower Mg olivines, crystallization from the carbonatite melt, or they may represent earlier crystallized phenocrysts in skarn. Oxidized olivines are easily diagnosed on the content of typomorphic admixtures, in particular, high MgO and NiO contents. It is difficult to recognize olivines from skarns and carbonatites due to the lack of high-precision analytical data. Extreme-Mg olivines from Pian di Celle (Italy) are close to the carbonatite subtype of olivines.

  8. Diffusion of He Interstitial and di-He Cluster at Grain Boundaries in Alpha-Fe

    SciTech Connect

    Gao, Fei; Heinisch, Howard L.; Kurtz, Richard J.

    2007-08-01

    A systematic molecular dynamics study of the diffusion mechanisms of He interstitial and their small clusters at two representative interfaces, sigma11 and sigma3, has been carried out in alpha-Fe. The diffusion coefficient of a He interstitial and the effective migration energies were determined, and the diffusion mechanisms of single interstitials and di-He interstitials are discussed in detail. A di-He interstitial cluster can kick out a self interstitial atom (SIA) at high temperatures, forming a He2V complex. The SIA migrates rapidly near interfaces, whereas the He2V complex is immobile at the temperatures considered. This small cluster may serve as a smallest nucleation for the formation of helium bubbles at interfaces.

  9. MeDiA: Mean Distance Association and Its Applications in Nonlinear Gene Set Analysis.

    PubMed

    Peng, Hesen; Ma, Junjie; Bai, Yun; Lu, Jianwei; Yu, Tianwei

    2015-01-01

    Probabilistic association discovery aims at identifying the association between random vectors, regardless of number of variables involved or linear/nonlinear functional forms. Recently, applications in high-dimensional data have generated rising interest in probabilistic association discovery. We developed a framework based on functions on the observation graph, named MeDiA (Mean Distance Association). We generalize its property to a group of functions on the observation graph. The group of functions encapsulates major existing methods in association discovery, e.g. mutual information and Brownian Covariance, and can be expanded to more complicated forms. We conducted numerical comparison of the statistical power of related methods under multiple scenarios. We further demonstrated the application of MeDiA as a method of gene set analysis that captures a broader range of responses than traditional gene set analysis methods.

  10. The Identification of Mono-, Di-, Tri-, and Tetragalactosyldiacylglycerols and their Natural Estolides in Oat Kernels†

    PubMed Central

    Moreau, Robert A.; Doehlert, Douglas C.; Welti, Ruth; Isaac, Giorgis; Roth, Mary; Tamura, Pamela; Nuñez, Alberto

    2014-01-01

    Oat kernels were extracted with methanol, and glycolipid-enriched fractions were prepared using silica solid phase extraction. Using direct infusion electrospray ionization (ESI) tandem mass spectrometry (MS), high performance liquid chromatography (HPLC)-ESI-MS, and HPLC-atmospheric pressure chemical ionization (APCI)-MS, we confirmed previous reports that digalactosyldiacylglycerol (DGDG) was the most abundant glycolipid in oat kernels and confirmed a previous report of the presence of a DGDG mono-estolide in oat kernels. In the current study we also identified several additional natural galactolipid estolides: two new DGDG estolides (di- and tri-estolides), two trigalactosyldiacylglycerol (TriGDG) estolides (mono- and di-estolides), and one tetragalactosyldiacylglycerol (TetraGDG) estolide (monoestolide). The levels of total galactolipid estolides in oat kernels were estimated to be about 29% of the total glycolipid fraction. To our knowledge, this report is the first evidence of natural diand tri-estolides of polar lipids. PMID:18481134

  11. 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.

  12. 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.

  13. Simultaneous di-oxygenation and denitrification in an internal circulation baffled bioreactor.

    PubMed

    Jiang, Ling; Tang, Yingxia; Sun, Weihua; Yi, Na; Zhang, Yongming; Shi, Hanchang; Rittmann, Bruce E

    2017-03-04

    An internal circulation baffled bioreactor was employed to realize simultaneous di-oxygenation of phthalic acid (PA) and denitrification of nitrate, which require aerobic and anoxic conditions, respectively. Adding a small concentration of succinate as an exogenous electron donor stimulated PA di-oxygenation, which produced readily oxidizable downstream products whose oxidation also enhanced denitrification of nitrate; succinate addition also stimulated denitrification. Depending on the concentration of PA, addition of 0.17 mM succinate increased the PA removal rate by 25 and 42%, while the corresponding nitrate removal rate was increased by 73 and 51%. UV/H2O2 advanced oxidation of PA had the same effects as adding succinate, since succinate is generated by UV/H2O2; this acceleration effect was approximately equivalent to adding 0.17 mM succinate.

  14. 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.

  15. DiGeorge syndrome associated with solitary median maxillary central incisor.

    PubMed

    Yang, Huai-Chih; Shyur, Shyh-Dar; Huang, Li-Hsin; Chang, Yi-Chi; Wen, Da-Chin; Liang, Pei-Hsuan; Lin, Mao-Tsair

    2005-01-01

    DiGeorge syndrome is a primary immunodeficiency disease characterized by dysgenesis of the thymus and parathyroid glands, conotruncal cardiac anomalies, and other dysmorphic features. Although most patients have a common microscopic deletion in chromosome 22q11.2, marked clinical variability exists. A solitary median maxillary central incisor (SMMCI) is a rare dental anomaly which may be an isolated occurrence or associated with congenital nasal airway abnormalities or holoprosencephaly. We report a patient with DiGeorge syndrome who was diagnosed at nearly 1 month of age and was later found to have a solitary median central incisor. Initially, the patient presented with recurrent episodes of respiratory distress attributed to partial airway obstruction, one of the phenotypic features of SMMCI. A fluorescence in situ hybridization study showed a chromosome 22q11.2 deletion.

  16. [DiGeorge syndrome/velcardiofacial syndrome: oral and maxillofacial surgery].

    PubMed

    Pradel, W; Bartsch, O; Müller, R; Lauer, G; Eckelt, U

    2003-09-01

    The DiGeorge syndrome/velocardiofacial syndrome is the most frequent chromosomal microdeletion syndrome. Partial deletion of chromosome 22q11 may lead to symptoms including facial dysmorphy, hypoparathyroidism, thymic aplasia, congenital heart disease, developmental retardation, and disturbance of speech development. According to the literature, 9% of patients have cleft palate, an additional 5% have a submucosal cleft, and a total of 32% show velopharyngeal insufficiency. We studied 64 children with a cleft, or with delayed speech development and a submucosal or occult cleft, for the presence of the 22q11deletion using fluorescent in situ hybridisation. Five patients had the 22q11 deletion. We conclude that patients presenting with nasal speech and additional anomalies should all be studied for the presence of submucosal or occult clefting and for the presence of the DiGeorge syndrome/velocardiofacial syndrome.

  17. 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.

  18. Misaligned spin and orbital axes cause the anomalous precession of DI Herculis.

    PubMed

    Albrecht, Simon; Reffert, Sabine; Snellen, Ignas A G; Winn, Joshua N

    2009-09-17

    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. One system, however-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. Here we report 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.

  19. Fifty ways to inhibit motility via cyclic di-GMP: the emerging Pseudomonas aeruginosa swarming story.

    PubMed

    McCarter, Linda L; Gomelsky, Mark

    2015-02-01

    There are numerous ways by which cyclic dimeric GMP (c-di-GMP) inhibits motility. Kuchma et al. (S. L. Kuchma, N. J. Delalez, L. M. Filkins, E. A. Snavely, J. P. Armitage, and G. A. O'Toole, J. Bacteriol. 197:420-430, 2015, http://dx.doi.org/10.1128/JB.02130-14) offer a new, previously unseen way of swarming motility inhibition in Pseudomonas aeruginosa PA14. This bacterium possesses a single flagellum with one rotor and two sets of stators, only one of which can provide torque for swarming. The researchers discovered that elevated levels of c-di-GMP inhibit swarming by skewing stator selection in favor of the nonfunctional, "bad" stators. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. CanDiD: A Framework for Linking Executive Function and Education.

    PubMed

    Kamkar, Niki H; Morton, J B

    2017-01-01

    The close association between executive functions (EFs) and educational achievement has led to the idea that targeted EF training might facilitate learning and goal-directed behavior in the classroom. The evidence that training interventions have long-lasting and transferable effects is however decidedly mixed (Melby-Lervåg and Hulme, 2013; Simons et al., 2016). The goal of the current paper is to propose a new CanDiD framework for re-thinking EF and its links to education. Based on findings from basic EF research, the proposed CanDiD framework highlights dynamic and contextual influences on EF and emphasizes the importance of development and individual differences for understanding these effects. Implications for remedial interventions and curriculum design are discussed.

  1. Antiinflammatory 2,6-di-tert-butyl-4-(2-arylethenyl)phenols.

    PubMed

    Lazer, E S; Wong, H C; Possanza, G J; Graham, A G; Farina, P R

    1989-01-01

    A series of 2,6-di-tert-butyl-4-(2-arylethenyl)phenols was prepared and examined for their ability to inhibit cyclooxygenase and 5-lipoxygenase in vitro and developing adjuvant arthritis in vivo in the rat. Structure-activity relationships are discussed. Among the best compounds is (E)-2,6-di-tert-butyl-4-[2-(3-pyridinyl)ethenyl]phenol (7d). It has an IC50 of 0.67 microM for cyclooxygenase and 2.7 microM for 5-lipoxygenase and an ED50 of 2.1 mg/kg in developing adjuvant arthritis. Additional in vivo data are reported for 7d.

  2. Temperature-dependent photochemistry of 1,3-diphenylpropenes. The di-pi-methane reaction revisited.

    PubMed

    Lewis, F D; Zuo, X; Kalgutkar, R S; Wagner-Brennan, J M; Miranda, M A; Font-Sanchis, E; Perez-Prieto, J

    2001-12-05

    The temperature-dependent photochemical behavior of 1,3-diphenylpropene and several of its 3-substituted derivatives has been investigated over a wide temperature range. The singlet state is found to decay via two unactivated processes, fluorescence and intersystem crossing, and two activated processes, trans,cis isomerization and phenyl-vinyl bridging. The latter activated process yields a diradical intermediate which partitions between ground-state reactant and formation of the di-pi-methane rearrangement product. Kinetic modeling of temperature-dependent singlet decay times and quantum yields of fluorescence, isomerization, di-pi-methane rearrangement, and nonradiative decay provides rate constants and activation parameters for each of the primary and secondary processes. Substituents at the 3-position are found to have little effect on the electronic spectra or unactivated fluorescence and intersystem crossing pathways. However, they do effect the activated primary and secondary processes. Thus, the product ratios are highly temperature dependent.

  3. 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.

  4. 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.

  5. Crystal structure of 2,4-di­amino-6-oxo-3,6-di­hydro­pyrimidin-1-ium p-toluene­sulfonate

    PubMed Central

    Mamallan, Krishnasamy; Tagore, Sadasivam Sharmila; Gomathi, Sundaramoorthy; Sethuraman, Velusamy

    2015-01-01

    In the title salt, C4H7N4O+·C7H7O3S−, the 2,6-di­amino-4-oxo-1,3-di­hydro­pyrimidin-1-ium cation inter­acts with the sulfonate group of the p-toluene­sulfonate anion via a pair of N—H⋯O hydrogen bonds, forming a hetero-synthon R 2 2(8) that mimics the role of a carboxyl­ate. The self-assembled cations form a homo-synthon R 2 1(6) motif which is further linked with the sulfonate anion via N—H⋯O hydrogen bonds to generate an R 3 2(10) ring motif. The three motifs are fused together and extended as supra­molecular ribbons along the b-axis direction. Adjacent ribbons are further linked via N—H⋯O hydrogen bonds to form an annulus, with an R 4 4(20) ring motif, resulting in a tunnel-like arrangement propagating along [010]. There are slipped parallel π–π stacking inter­actions [inter-centroid distance = 3.6539 (7) Å], between the tunnel-like polymer chains, forming slabs parallel to (100). PMID:25995859

  6. 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.

  7. Novel octahedral Pt(IV) complex with di-n-propyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoato ligand exerts potent immunomodulatory effects.

    PubMed

    Miljković, Djordje; Poljarević, Jelena M; Petković, Filip; Blaževski, Jana; Momčilović, Miljana; Nikolić, Ivana; Saksida, Tamara; Stošić-Grujičić, Stanislava; Grgurić-Šipka, Sanja; Sabo, Tibor J

    2012-01-01

    We have recently reported that a novel octahedral Pt(IV) complex with di-n-propyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoato ligand has a potent cytotoxic effect on glioma, melanoma and fibrosarcoma cell lines. In this work, we investigated the influence of the Pt(IV) compound on immune cells. We determined its effect on the viability of spleen cells and lymph node cells and on their capability to produce interferon (IFN)-γ and interleukin (IL)-17. Also, we researched the compound's impact on peritoneal macrophages and generation of NO in these cells. Our results show that the complex has limited influence on cell viability of immune cells, but profound inhibitory effect on the production of examined immune mediators. These results are valuable as they show that the novel Pt(IV) complex applied in concentrations which are effective against tumor cells do not affect immune cell viability. Moreover, they also imply that the complex has immunomodulatory properties.

  8. Chamber studies on mass-transfer of di(2-ethylhexyl)phthalate (DEHP) and di- n-butylphthalate (DnBP) from emission sources into house dust

    NASA Astrophysics Data System (ADS)

    Schripp, Tobias; Fauck, Christian; Salthammer, Tunga

    2010-08-01

    For a number of phthalates and especially for di(2-ethylhexyl)phthalate (DEHP), surprisingly high house dust concentrations are reported in the literature. Therefore, the uptake of the most prominent compounds DEHP and di- n-butylphthalate (DnBP) from plasticized indoor materials into house dust samples of different organic content has been experimentally determined. The experiments have been performed within 45 days which is sufficient for the more volatile phthalate (DnBP) to reach equilibrium conditions. DnBP reaches considerably higher concentrations in the chamber air compared to real room measurements and, thus, also elevated dust concentrations. In contrast, the mass transfer of DEHP in the dust via the gas phase was significantly lower. However, small chamber experiments showed elevated mass transfer of DEHP in case of direct contact between emission source and sink. This aspect is experimentally determined using an plasticized PVC polymer with and without direct contact to house dust. A transfer into the dust could be observed in dependence of the initial concentration in the material. However, the results do not allow the differentiation between the two uptake mechanisms via capillary forces and contact to the material's boundary layer. The results illustrate that the reasons for elevated DEHP concentrations in dust indoors can be traced back to direct contact of source and sink, abrasion from the source, and transport via airborne particles.

  9. 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

    2015-02-05

    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.

  10. Perioperative management of patients with DiGeorge syndrome undergoing cardiac surgery.

    PubMed

    Yeoh, Tze Yeng; Scavonetto, Federica; Hamlin, Ryan J; Burkhart, Harold M; Sprung, Juraj; Weingarten, Toby N

    2014-08-01

    DiGeorge syndrome is a genetic disorder with multisystem involvement resulting in craniofacial and cardiac anomalies and parathyroid and immune system dysfunction. This study describes perioperative management of a large cohort of patients with DiGeorge syndrome undergoing cardiac surgery. Retrospective cohort study. Major academic tertiary institution. The medical records of patients diagnosed with DiGeorge syndrome and undergoing cardiac surgery at this institution, from January 1, 1976, to July 31, 2012, were reviewed for phenotypic characteristics and intraoperative and postoperative complications, with specific attention to hemodynamic instability, perioperative perturbations of plasma calcium homeostasis, and airway difficulty. None. Sixty-two patients underwent 136 cardiac surgical procedures; 47 patients (76%) had multiple operations. Sternotomies for reoperations often were complex (8 complicated by vascular injury or difficulty achieving hemostasis and 5 requiring bypass before sternotomy). Two patients had persistent hypocalcemia intraoperatively, requiring infusion of calcium chloride, and hypocalcemia developed postoperatively in 8 patients. Prolonged mechanical ventilation (>24 hours) was required after 48 procedures (35%), and 25 (18%) required prolonged inotropic support (>72 hours). Infectious complications occurred after 31 procedures (23%). There was no in-hospital or 30-day mortality. Patients with DiGeorge syndrome often have complex cardiac anomalies that require surgical repair. The postoperative course is notable for the frequent need for prolonged respiratory and hemodynamic support. Patients can develop hypocalcemia and may require calcium supplementation. Immunodeficiencies may be associated with the increased rate of postoperative infections and may dictate the need for specific transfusion management practices. © 2014 Elsevier Inc. All rights reserved.

  11. 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.

  12. New DiFX Software Correlator Cluster at Bonn and Summary of Recent Activities

    NASA Astrophysics Data System (ADS)

    Müskens, Arno; Alef, Walter; Bertarini, Alessandra; Bernhart, Simone; La Porta, Laura; Rottmann, Helge; Bruni, Gabriele; Schüler, Torben; Brisken, Walter

    2016-12-01

    We report on the status of the Bonn Correlator Center for the period 2015/2016. The correlator center has been operated jointly by the Max Planck Institute for Radio Astronomy (MPIfR) in Bonn and the Federal Agency for Cartography and Geodesy in Frankfurt with support from the Institute of Geodesy and Geoinformation in Bonn for more than 25 years. Since 2010 we have been using the DiFX software correlator te{Deller2011

  13. [Clinical features and molecular diagnosis of three patients with DiGeorge anomaly].

    PubMed

    Sun, Jin-qiao; Wang, Lai-shuan; Qi, Chun-hua; Ying, Wen-jing; Guo, Xiao-hong; Liu, Dan-ru; Hui, Xiao-ying; Liu, Fang; Cao, Yun; Luo, Fei-hong; Wang, Xiao-chuan

    2012-12-01

    To investigate the clinical features and molecular diagnostic methods of three patients with DiGeorge anomaly. The clinical manifestations and immunological features of the three cases with DiGeorge anomaly were analyzed. We detected the chromosome 22q11.2 gene deletion by fluorescence in situ hybridization (FISH). (1) CLINICAL MANIFESTATIONS: All three cases had varying degrees of infection, congenital heart disease and small thymus by imaging; two cases had significant hypocalcemia (1.11 mmol/L and 1.22 mmol/L, respectively), accompanied by convulsions; only 1 case had cleft palate and all had no significant facial deformity. (2) Immunological characteristics: All three cases had varying degrees of T-cell immune function defects (percentage of T lymphocytes was 24% - 43%, absolute count was 309 - 803/µl), and levels of immunoglobulin G, A, M, and percent of B lymphocytes and absolute count were normal. (3) Detection of the chromosome 22q11.2 gene deletion: 400 cells of each case were detected. All cells showed two green and one red hybridization signal, indicating the presence of gene deletions in chromosome 22q11.2. (4) OUTCOME: All three cases were treated with thymosin, and appropriate clinical intervention for cardiac malformations, hypocalcemia, and were followed-up for 4 - 18 months, the prognosis was good. DiGeorge anomaly showed diverse clinical manifestations. We should consider the disease if patients had congenital heart disease, thymic hypoplasia, hypocalcemia and/or impaired immune function. FISH for detecting chromosome 22q11.2 gene deletion can be used as accurate and rapid diagnostic method. Thymosin treatment and other clinical intervention may help to improve the prognosis of patients with partial DiGeorge anomaly.

  14. 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.

  15. 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.

  16. Autoimmune thrombocytopenic purpura in partial DiGeorge syndrome: case presentation.

    PubMed

    Hernández-Nieto, Leticia; Yamazaki-Nakashimada, Marco Antonio; Lieberman-Hernández, Esther; Espinosa-Padilla, Sara Elva

    2011-08-01

    The absence of an appropriate central tolerance in primary immunodeficiencies favors proliferation of autoreactive lymphocyte clones, causing a greater incidence of autoimmunity. Del 22q11.2 syndrome presents an increased incidence of allergic and autoimmune diseases. One of the most relevant and frequent immune manifestations is autoimmune thrombocytopenia. We present the case of a pediatric patient with autoimmune thrombocytopenia due to the immunological dysregulation observed in partial DiGeorge syndrome.

  17. Dermatological clues to the diagnosis of atypical complete DiGeorge syndrome.

    PubMed

    Seminario-Vidal, Lucia; Kole, Lauren; Knapp, Charles; Fort, Prem; Kankirawatana, Suthida; Atkinson, T Prescott; McKay, Kristopher M; Theos, Amy

    2016-11-15

    Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis.

  18. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients.

    PubMed

    Markert, M Louise; Sarzotti, Marcella; Ozaki, Daniel A; Sempowski, Gregory D; Rhein, Maria E; Hale, Laura P; Le Deist, Francoise; Alexieff, Marilyn J; Li, Jie; Hauser, Elizabeth R; Haynes, Barton F; Rice, Henry E; Skinner, Michael A; Mahaffey, Samuel M; Jaggers, James; Stein, Leonard D; Mill, Michael R

    2003-08-01

    Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.

  19. [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.

  20. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.

    PubMed

    Haire, R N; Buell, R D; Litman, R T; Ohta, Y; Fu, S M; Honjo, T; Matsuda, F; de la Morena, M; Carro, J; Good, R A

    1993-09-01

    Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.

  1. Synergistic Physical Properties of Co-Cured Networks Formed from Di- and Tri-cyanate Esters

    DTIC Science & Technology

    2013-09-01

    Guenthner , Josiah T. Reams, Kevin R. Lamison, Sean M. Ramirez David D. Swanson, Gregory R. Yandek, Christopher M. Sahagun Matthew C. Davis Joseph M...Co-Cured Networks Formed from Di- and Tri-cyanate Esters” Andrew J. Guenthner * 1 , Josiah T. Reams 2 , Kevin R. Lamison 2 , Sean M. Ramirez 2... Guenthner , A. J.; Groshens, T. J.; Reams, J. T.; Mabry, J. M., J. Polym. Sci. Part A, Polym. Chem. 2012, 50, 4127-4136. S2. Guenthner , A. J.; Davis, M

  2. DiAs User Interface: A Patient-Centric Interface for Mobile Artificial Pancreas Systems

    PubMed Central

    Keith-Hynes, Patrick; Guerlain, Stephanie; Mize, Benton; Hughes-Karvetski, Colleen; Khan, Momin; McElwee-Malloy, Molly; Kovatchev, Boris P.

    2013-01-01

    Background Recent in-hospital studies of artificial pancreas (AP) systems have shown promising results in improving glycemic control in patients with type 1 diabetes mellitus. The next logical step in AP development is to conduct transitional outpatient clinical trials with a mobile system that is controlled by the patient. In this article, we present the user interface (UI) of the Diabetes Assistant (DiAs), an experimental smartphone-based mobile AP system, and describe the reactions of a round of focus groups to the UI. This work is an initial inquiry involving a relatively small number of potential users, many of whom had never seen an AP system before, and the results should be understood in that light. Methods We began by considering how the UI of an AP system could be designed to make use of the familiar touch-based graphical UI of a consumer smartphone. After developing a working prototype UI, we enlisted a human factors specialist to perform a heuristic expert analysis. Next we conducted a formative evaluation of the UI through a series of three focus groups with N = 13 potential end users as participants. The UI was modified based upon the results of these studies, and the resulting DiAs system was used in transitional outpatient AP studies of adults in the United States and Europe. Results The DiAs UI was modified based on focus group feedback from potential users. The DiAs was subsequently used in JDRF- and AP@Home-sponsored transitional outpatient AP studies in the United States and Europe by 40 subjects for 2400 h with no adverse events. Conclusions Adult patients with type 1 diabetes mellitus are able to control an AP system successfully using a patient-centric UI on a commercial smartphone in a transitional outpatient environment. PMID:24351168

  3. Prevention of gastric mucosal lesions in rats by tri-potassium di-citrato bismuthate.

    PubMed

    Malandrino, S; Campagnoli, G; Borsa, M; Guidoboni, R; Tonon, G C

    1984-01-01

    Tri-potassium di-citrato bismuthate given intragastrically to rats 60 min before administration of necrotizing agents such as 85% ethanol, 0.2 N sodium hydroxide or acidified indomethacin, reduced the formation of mucosal lesions dose-dependently. Prostaglandin I2 (PGI2)-like material, determined by bioassay, was higher in the gastric mucosa of animals treated with bismuth subcitrate complex than in control animals.

  4. Spatial distributions of airborne di-carbonyls in urban and rural areas in China

    NASA Astrophysics Data System (ADS)

    Lui, K. H.; Dai, Wen-Ting; Chan, C. S.; Ho, Steven Sai Hang; Cao, Jun-Ji; Lee, S. C.; Ho, K. F.

    2017-04-01

    Gaseous glyoxal and methylglyoxal concentrations were characterized in nine cities of China during 2010-2011. The average summer (winter) glyoxal and methylglyoxal concentrations were 36.4-178.4 (12.3-241.4) and 67.8-359.4 (28.4-530.0) ng/m3, respectively. In summer, the highest average glyoxal concentration was in Guangzhou (GZ), while the lowest was in Shanghai (SH). In winter, Xiamen (XM) showed the highest average methylglyoxal concentration and Yantai (YT) reported the lowest. Both di-carbonyls showed distinct seasonal variations. The maximum average methylglyoxal concentration was approximately twice as much as glyoxal, which is consistent with the results of other studies. Glyoxal-to-methylglyoxal ratios showed that there was a consistent direct source of emissions in remote areas such as Qinghai Lake and Lhasa in both seasons (r ≥ 0.9). Pearson's correlation analysis suggested possible similar sources formation (R ≥ 0.7) for the two di-carbonyls in winter. Multiple linear regression analyses demonstrated that every 1 °C temperature increase could lead to a > 2% increase in the concentration of the di-carbonyls in both seasons. There was a greater percentage gain for glyoxal in winter than in summer for the same temperature increase. The northeast monsoon occurs in winter, and for every 1 ms- 1 increase in wind speed, > 20% of the di-carbonyls can be transferred out of China. This study is useful to understand about the secondary organic aerosol formation in the areas, the statistical analysis can provide information about the relationships between these carbonyls in atmosphere.

  5. 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.

  6. Domino Staudinger/aza-Wittig/Mannich Reaction: An Approach to Diversity of Di- and Tetrahydropyrrole Scaffolds.

    PubMed

    Pavlova, Anna S; Ivanova, Olga A; Chagarovskiy, Alexey O; Stebunov, Nikolay S; Orlov, Nikolay V; Shumsky, Alexey N; Budynina, Ekaterina M; Rybakov, Victor B; Trushkov, Igor V

    2016-12-12

    A highly efficient and selective domino reaction producing valuable di- and tetrahydropyrrole-based skeletons from azidoethyl-substituted CH-acids and (thio)carbonyl compounds has been developed. By involving the additional functional groups in starting compounds into the domino reaction or postmodification of the primary reaction products, the simple construction of the pharmaceutically relevant three- and polycyclic azaheterocyclic scaffolds was demonstrated. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 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.

  8. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    DOE PAGES

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; ...

    2015-12-28

    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 cellularmore » 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.« less

  9. 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

  10. New Functions and Subcellular Localization Patterns of c-di-GMP Components (GGDEF Domain Proteins) in B. subtilis.

    PubMed

    Bedrunka, Patricia; Graumann, Peter L

    2017-01-01

    The universal and pleiotropic cyclic dinucleotide second messenger c-di-GMP is most prominently known to inversely regulate planktonic and sessile lifestyles of Gram-negative species. In the Gram-positive model organism Bacillus subtilis, intracellular c-di-GMP levels are modulated by a concise set of three diguanylate cylases (DgcK, DgcP, DgcW) and one phosphodiesterase (PdeH). Two recent studies have reported the negative influence of the c-di-GMP receptor DgrA (PilZ domain protein) on swarming motility indicating a conserved role of this second messenger across the bacterial domain. However, it has been suggested that the degenerated GGDEF protein YdaK and the inactive EAL domain protein YkuI may also function as c-di-GMP receptors regulating potentially other processes than motility. Here we describe a novel c-di-GMP dependent signaling network in B. subtilis regulating the production of an unknown exopolysaccharide (EPS) that leads to strongly altered colony morphologies upon overproduction. The network consists of the c-di-GMP receptor YdaK and the c-di-GMP synthetase DgcK. Both proteins establish a spatially close signal-effector cluster at the membrane. The cytoplasmic DgcP synthetase can complement for DgcK only upon overproduction, while the third c-di-GMP synthetase, DgcW, of B. subtilis is not part of the signaling pathway. Removal of the regulatory EAL domain from DgcW reveals a distinct function in biofilm formation. Therefore, our study is compatible with the "local pool signaling" hypothesis, but shows that in case of the yda operon, this can easily be overcome by overproduction of non-cognate DGCs, indicating that global pools can also confer signals to regulatory circuits in a Gram-positive bacterium.

  11. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

    PubMed Central

    Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs

    2017-01-01

    ABSTRACT The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli. This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. PMID:28928205

  12. Inactivation of cyclic Di-GMP binding protein TDE0214 affects the motility, biofilm formation, and virulence of Treponema denticola.

    PubMed

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

    2013-09-01

    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.

  13. 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

  14. Microcrystals engineering using assemblies of di-protonated meso-tetraphenylporphine dimers under Zundel cations operation

    NASA Astrophysics Data System (ADS)

    Udal'tsov, Alexander V.

    2015-03-01

    New approach based on the usage of self-organized assemblies of di-protonated meso-tetraphenylporphine (TPP) dimers under Zundel cations action is suggested for the microcrystals engineering. Properties of the assemblies consisting of water and the protonated dimers, as produced in aqueous HCl in the presence of a small concentration of water-soluble organic solvent were investigated by UV-Vis and infrared spectroscopy and atomic force microscopy (AFM) in thin films. The self-organized assemblies consisting of water and di-protonated TPP dimers looked like long rods produced green crystals. These crystals were found by light microscopy. The ordered assembled structures crystallized into thin layers at open air at relative humidity of least 60%. Three acts of the microcrystals engineering actions are needed to obtain the green crystals that are (i) self-assembling of protonated TPP dimers under Zundel cations operation; (ii) generation of pure rod precursor in the di-protonated state and (iii) application of gaseous water to initiate the crystallization in order to Zundel cations action in the surface layer could occur. The size of the green crystals produced by the self-organized assemblies varies within 30-35 μm.

  15. Crystal structure of N,N′-di­benzyl­pyromellitic diimide

    PubMed Central

    Im, Hansu; Moon, Suk-Hee; Kim, Tae Ho; Park, Ki-Min

    2016-01-01

    The title compound, C24H16N2O4 [systematic name: 2,6-di­benzyl­pyrrolo­[3,4-f]iso­indole-1,3,5,7(2H,6H)-tetra­one], consists of a central pyromellitic di­imide moiety with terminal benzyl groups at the N-atom positions. The mol­ecule is located about an inversion centre, so the asymmetric unit contains one half-mol­ecule. In the mol­ecule, both terminal phenyl groups, tilted by 72.97 (4)° with respect to the mean plane of the central pyromellitic di­imide moiety (r.m.s. deviation = 0.0145 Å), are oriented away from each other, forming an elongated S-shaped conformation. In the crystal, mol­ecules are connected via weak C—H⋯O hydrogen bonds and C—H⋯π inter­actions, resulting in the formation of supra­molecular layers extending parallel to the ab plane. PMID:27980836

  16. 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

  17. DiGeorge Syndrome Presenting as Hypocalcaemia-Induced Seizures in Adulthood.

    PubMed

    Zammit, Adrian; Grech Marguerat, Deborah; Psaila, Josephine; Attard, Alexander

    2013-01-01

    Introduction. DiGeorge syndrome is a developmental defect commonly caused by a microdeletion on the long arm of chromosome 22 or less frequently by a deletion of the short arm of chromosome 10. Case report. We report a case of a gentleman with mild dysmorphic features who presented with hypocalcaemia-induced seizures and an associated thyroid mass with a background of learning difficulties and abnormal immune function. Discussion. DiGeorge syndrome was initially described in 1967 by Angelo DiGeorge. The majority of cases are due to a novel mutation. The resulting learning difficulties, congenital heart disease, palatal abnormalities, hypoplasia/aplasia of the parathyroid and thymus glands, and immune deficiency generally lead to diagnosis in childhood. Presentation in adulthood is rare but must be borne in mind when dealing with cases of hypocalcaemia even in the absence of florid phenotypic features. A link with malignant disease has also been reported and should lead to prompt investigation of concerning masses.

  18. [Analysis of compiling date of Huang di nei jing (Huangdi's Internal Classic)].

    PubMed

    Zhang, W B; Gao, Y T; Li, H Y

    2017-05-28

    There are Seven Medical Classics recorded in the Han shu Yi wen zhi(Bibliography in Annals of the Han Dynasty), among which the 18-volume Huang di nei jing (Huangdi's Internal Classic) is not the current edition of Ling shu (Miraculous Pivot) and Su wen(Plain Questions). The present edition of Huang di nei jing containing these two works might be merged in the Eastern Han Dynasty, benefited from the invention of Cai Lun's papermaking technique and the development of Nine needles, especially filiform needle manufacturing. Huang di nei jing was compiled on the basis of two major integrations: The first was joined by some medical experts such as Bian Que and tai yi ling (minister of imperial physicians) of the Qin State by using the language in the Warring States, contributing mainly to the theoretical system and forming its basic academic framework; The second was the second Royal book-collating activity in the Eastern Han Dynasty (100-110), which had revised the seven volumes of Chinese Medical Classics and incorporated them into two parts, Ling Shu and Su Wen, together with Bian Que's medical works and the new contents from the introductory Chapter on Nine Needles and Twelve Yuan(origin) Acupoints.

  19. A Basic Behavior of CNG DI Combustion in a Spark-Ignited Rapid Compression Machine

    NASA Astrophysics Data System (ADS)

    Huang, Zuohua; Shiga, Seiichi; Ueda, Takamasa; Jingu, Nobuhisa; Nakamura, Hisao; Ishima, Tsuneaki; Obokata, Tomio; Tsue, Mitsuhiro; Kono, Michikata

    A basic characteristics of compressed natural gas direct-injection (CNG DI) combustion was studied by using a rapid compression machine. Results show that comparing with homogeneous mixture, CNG DI has short combustion duration, high pressure rise due to combustion, and high rate of heat release, which are considered to come from the charge stratification and the gas flow generated by the fuel injection. CNG DI can realize extremely lean combustion which reaches 0.03 equivalence ratio, φ. Combustion duration, maximum pressure rise due to combustion and combustion efficiency are found to be insensitive to the injection modes. Unburned methane showed almost the same level as that of homogeneous mixture combustion. CO increased steeply with the increase in φ when φ was greater than 0.8 due to the excessive stratification, and NOx peak value shifted to the region of lower φ. Combustion inefficiency maintains less than 0.08 in the range of φ from 0.1 to 0.9 and increases at very low φ due to bulk quenching and at higher φ due to excessive stratification. The combustion efficiency estimated from combustion products shows good agreement with that of heat release analysis.

  20. Cyclic-di-GMP signalling meets extracellular polysaccharide synthesis in Bacillus subtilis.

    PubMed

    Kampf, Jan; Stülke, Jörg

    2017-06-01

    In order to resist harmful environmental conditions, many bacteria form multicellular aggregates called biofilms. In these biofilms, they protect themselves in a self-produced matrix consisting of extracellular polysaccharides, proteins and DNA. In many bacteria, biofilm formation is stimulated in the presence of the second messenger cyclic di-GMP. In this issue of Environmental Microbiology Reports, Bedrunka and Graumann have studied matrix production by the proteins encoded in the Bacillus subtilis ydaJKLMN operon. For the first time, they were able to provide a link between c-di-GMP signalling and matrix production in this bacterium. The work demonstrates that the c-di-GMP receptor protein YdaK forms a membrane-bound complex with the YdaM and YdaN proteins, and that this interaction with YdaK is required for polysaccharide production by YdaL, YdaM and YdaN. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. The effect of real and virtual photons in the di-lepton channel at the LHC

    NASA Astrophysics Data System (ADS)

    Accomando, Elena; Fiaschi, Juri; Hautmann, Francesco; Moretti, Stefano; Shepherd-Themistocleous, Claire H.

    2017-07-01

    We present a study of di-lepton production at the CERN Large Hadron Collider with a particular focus on the contribution resulting from both real and virtual photons in the initial state. We discuss the region of phase space in which the invariant mass of the lepton pair is of the order of several TeV, where searches for new physics phenomena yielding a di-lepton signature are presently carried out. We study both the yield and associated uncertainties for all possible topologies in photon-induced di-lepton production and compare these with what is expected in the standard Drell-Yan channel, where quark-antiquark pairs are responsible for the production of lepton pairs. We analyse the impact of these QED contributions on the expected Standard Model background and on searches for new physics. In this latter case, we use the production of an extra heavy Z‧-boson predicted by the Sequential Standard Model (SSM) as a benchmark process.

  2. "Pecorino di Filiano" cheese as a selective habitat for the yeast species, Debaryomyces hansenii.

    PubMed

    Capece, A; Romano, P

    2009-06-30

    The composition of yeast microflora in artisanal "Pecorino di Filiano" cheese, a typical product of the Basilicata region of Southern Italy, was studied during ripening. The isolates were identified by restriction analysis of the 18S rDNA amplified region with the combined use of Hinf I and Cfo I enzymes. The majority of the isolates were identified as Debaryomyces hansenii, whereas two yeasts were identified as Kluyveromyces lactis and one as Dekkera anomala. To evaluate natural biodiversity, D. hansenii "Pecorino di Filiano" isolates were submitted to genetic and technological characterization. RAPD-PCR analysis with P80 (5CGCGTGCCCA3) primer revealed significant polymorphism among D. hansenii isolates. About 30% of the isolates showed single molecular profiles, whereas the other D. hansenii yeasts were separated into three main patterns, differing for both the ripening time and the isolation source. Furthermore, the yeasts showed significant variability in their, "proteolytic activity". This work demonstrated the high predominance of D. hansenii among the yeast population of "Pecorino di Filiano" cheese, probably in consequence of the traditional salting process, which was selected for this salt tolerant species. This preliminary study allowed us to isolate autochthonous D. hansenii yeasts potentially useful as starters for the production of this artisanal cheese.

  3. 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.

  4. Synthesis and structure-activity relationship of oleanolic mono- or di-glycosides against Magnaporthe oryzae.

    PubMed

    Huo, G; Liu, C; Hui, Y; Chen, X; Xiao, D

    2016-09-23

    Saponins are naturally-occurring units with broad diversity and are usually recognized as phytoanticipins. In order to develop new saponin chemical entities with high activity against Magnaporthe oryzae, we selected oleanolic acid (OA), which has wide natural distribution and rich content in plants. We used the ability of OA to act as an aglycone for glycosylation to obtain information on the structure-activity relationship (SAR) for rational molecular pesticide design. Oleanolic mono- or di-glycosides were synthesized at either the C3-hydroxy and/or C28-carboxyl position, using trichloroacetimidate or glycosyl bromide donors, respectively. Structures were confirmed by [(1)H]-,[(13)C]-NMR. Furthermore, the activity of the synthesized glycosides against M. oryzae was assessed in vitro, based on the mycelium growth rate. The twenty five oleanolic mono- or di-glycosides comprised fourteen saponins with 3-monosaccharide residue 1a-1n, six saponins with 28-monosaccharide residue 2a-2f, and five saponins with 3, 28-monosaccharide residue 3a-3e; all showed different activities against M. oryzae according to their different structures. We concluded that the optimal oleanolic mono- and di-glycoside structure for activity against M. oryzae is a C3 connection of a hexose such as mannose, galactose, or glucose, in combination with a C28 connection to a small group such as allyl or a C3 connection to a pentose accompanied by a larger group such as another pentose or heptenyl at C28.

  5. 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

  6. c-di-AMP modulates Listeria monocytogenes central metabolism to regulate growth, antibiotic resistance and osmoregulation.

    PubMed

    Whiteley, Aaron T; Garelis, Nicholas E; Peterson, Bret N; Choi, Philip H; Tong, Liang; Woodward, Joshua J; Portnoy, Daniel A

    2017-04-01

    Cyclic diadenosine monophosphate (c-di-AMP) is a conserved nucleotide second messenger critical for bacterial growth and resistance to cell wall-active antibiotics. In Listeria monocytogenes, the sole diadenylate cyclase, DacA, is essential in rich, but not synthetic media and ΔdacA mutants are highly sensitive to the β-lactam antibiotic cefuroxime. In this study, loss of function mutations in the oligopeptide importer (oppABCDF) and glycine betaine importer (gbuABC) allowed ΔdacA mutants to grow in rich medium. Since oligopeptides were sufficient to inhibit growth of the ΔdacA mutant we hypothesized that oligopeptides act as osmolytes, similar to glycine betaine, to disrupt intracellular osmotic pressure. Supplementation with salt stabilized the ΔdacA mutant in rich medium and restored cefuroxime resistance. Additional suppressor mutations in the acetyl-CoA binding site of pyruvate carboxylase (PycA) rescued cefuroxime resistance and resulted in a 100-fold increase in virulence of the ΔdacA mutant. PycA is inhibited by c-di-AMP and these mutations prompted us to examine the role of TCA cycle enzymes. Inactivation of citrate synthase, but not down-stream enzymes suppressed ΔdacA phenotypes. These data suggested that c-di-AMP modulates central metabolism at the pyruvate node to moderate citrate production and indeed, the ΔdacA mutant accumulated six times the concentration of citrate present in wild-type bacteria.

  7. Big Data from Europe's Natural Science Collections through DiSSCo

    NASA Astrophysics Data System (ADS)

    Addink, Wouter; Koureas, Dimitris; Casino, Ana

    2017-04-01

    DiSSCo, a Distributed System of Scientific Collections, will be a Research Infrastructure delivering big data describing the history of Planet Earth. Approximately 1.5 billion biological and geological specimens, representing the last 300 years of scientific study on the natural world, reside in collections all over Europe. These span 4.5 billion years of history, from the formation of the solar system to the present day. In the European landscape of environmental Research Infrastructures, different projects and landmarks describe services that aim at aggregating, monitoring, analysing and modelling geo-diversity information. The effectiveness of these services, however, is based on the quality and availability of primary reference data that today is scattered and uncomplete. DiSSCo provides the required bio-geographical, taxonomic and species trait data at the level of precision and accuracy required to enable and speed up research for the rapidly growing seven grand societal challenges that are priorities of the Europe 2020 strategy. DiSSCo enables better connections between collection data and observations in biodiversity observation networks, such as EU BON and GEOBON. This supports research areas like long term ecological research, for which the continuity and long term research is a strength of biological collections.

  8. The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs.

    PubMed

    Shanahan, Carly A; Strobel, Scott A

    2012-12-14

    The ability of bacteria to adapt to a changing environment is essential for their survival. One mechanism used to facilitate behavioral adaptations is the second messenger signaling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP). c-di-GMP is widespread throughout the bacterial domain and plays a vital role in regulating the transition between the motile planktonic lifestyle and the sessile biofilm forming state. This second messenger also controls the virulence response of pathogenic organisms and is thought to be connected to quorum sensing, the process by which bacteria communicate with each other. The intracellular concentration of c-di-GMP is tightly regulated by the opposing enzymatic activities of diguanlyate cyclases and phosphodiesterases, which synthesize and degrade the second messenger, respectively. The change in the intracellular concentration of c-di-GMP is directly sensed by downstream targets of the second messenger, both protein and RNA, which induce the appropriate phenotypic response. This review will summarize our current state of knowledge of c-di-GMP signaling in bacteria with a focus on protein and RNA binding partners of the second messenger. Efforts towards the synthesis of c-di-GMP and its analogs are discussed as well as studies aimed at targeting these macromolecular effectors with chemically synthesized cyclic dinucleotide analogs.

  9. Mutation in the C-di-AMP cyclase dacA affects fitness and resistance of methicillin resistant Staphylococcus aureus.

    PubMed

    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.

  10. Highly efficient enzymatic preparation of c-di-AMP using the diadenylate cyclase DisA from Bacillus thuringiensis.

    PubMed

    Zheng, Cao; Wang, Jieping; Luo, Yunchao; Fu, Yang; Su, Jianmei; He, Jin

    2013-05-10

    Cyclic 3',5'-diadenosine monophosphate (c-di-AMP) is a newly recognized bacterial nucleotide second messenger molecule. In addition, it has been shown to be a potential vaccine adjuvant. Although multiple methods are available for c-di-AMP synthesis, the yields are low and the purification procedures are laborious. Here, we report an enzymatic method for more efficient and economical c-di-AMP synthesis using a diadenylate cyclase DisA from Bacillus thuringiensis BMB 171 (btDisA). After overexpression and purification of btDisA, the enzyme-catalyzed reaction conditions were further investigated. Under the optimum conditions, in which 100mM CHES (pH 9.5) containing 2μM btDisA, 10mM ATP, and 10mM MgCl2 was incubated at 50°C for 4h, a high conversion rate of c-di-AMP was obtained. Coupling this process with HPLC purification and lyophilization yielded 100mg of highly pure c-di-AMP that was harvested in white powder form from a 50mL enzyme-catalyzed reaction system. The protocol is not only directly applicable for preparing abundant amounts of c-di-AMP for extensive biochemical and immunological use, but can also be scaled up to meet the requirements for medical applications.

  11. A di- and tripeptide transport system can supply Listeria monocytogenes Scott A with amino acids essential for growth.

    PubMed Central

    Verheul, A; Hagting, A; Amezaga, M R; Booth, I R; Rombouts, F M; Abee, T

    1995-01-01

    Listeria monocytogenes takes up di- and tripeptides via a proton motive force-dependent carrier protein. This peptide transport system resembles the recently cloned and sequenced secondary di- and tripeptide transport system of Lactococcus lactis (A. Hagting, E. R. S. Kunji, K. J. Leenhouts, B. Poolman, and W. N. Konings, J. Biol. Chem. 269:11391-11399, 1994). The peptide permease of L. monocytogenes has a broad substrate specificity and allows transport of the nonpeptide substrate 5-aminolevulinic acid, the toxic di- and tripeptide analogs, alanyl-beta-chloroalanine and alanyl-alanyl-beta-chloroalanine, and various di- and tripeptides. No extracellular peptide hydrolysis was detected, indicating that peptides are hydrolyzed after being transported into the cell. Indeed, peptidase activities in response to various synthetic substrates were detected in cell extracts obtained from L. monocytogenes cells grown in brain heart infusion broth or defined medium. The di- and tripeptide permease can supply L. monocytogenes with essential amino acids for growth and might contribute to growth of this pathogen in various foods where peptides are supplied by proteolytic activity of other microorganisms present in these foods. Possible roles of this di- and tripeptide transport system in the osmoregulation and virulence of L. monocytogenes are discussed. PMID:7887604

  12. 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

  13. The bacterial second messenger c-di-GMP: Probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs

    PubMed Central

    Shanahan, Carly A.; Strobel, Scott A.

    2013-01-01

    The ability of bacteria to adapt to a changing environment is essential for their survival. One mechanism used to facilitate behavioral adaptations is the second messenger signaling molecule bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP). c-di-GMP is widespread throughout the bacterial domain and plays a vital role in regulating the transition between the motile planktonic lifestyle and the sessile biofilm forming state. This second messenger also controls the virulence response of pathogenic organisms and is thought to be connected to quorum sensing, the process by which bacteria communicate with each other. The intracellular concentration of c-di-GMP is tightly regulated by the opposing enzymatic activities of diguanlyate cyclases and phosphodiesterases, which synthesize and degrade the second messenger, respectively. The change in the intracellular concentration of c-di-GMP is directly sensed by downstream targets of the second messenger, both protein and RNA, which induce the appropriate phenotypic response. This review will summarize our current state of knowledge of c-di-GMP signaling in bacteria with a focus on protein and RNA binding partners of the second messenger. Efforts towards the synthesis of c-di-GMP and its analogs are discussed as well as studies aimed at targeting these macromolecular effectors with chemically synthesized cyclic dinucleotide analogs. PMID:23108253

  14. Two DHH Subfamily 1 Proteins in Streptococcus pneumoniae Possess Cyclic Di-AMP Phosphodiesterase Activity and Affect Bacterial Growth and Virulence

    PubMed Central

    Bai, Yinlan; Yang, Jun; Eisele, Leslie E.; Underwood, Adam J.; Koestler, Benjamin J.; Waters, Christopher M.; Metzger, Dennis W.

    2013-01-01

    Cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP) are signaling molecules that play important roles in bacterial biology and pathogenesis. However, these nucleotides have not been explored in Streptococcus pneumoniae, an important bacterial pathogen. In this study, we characterized the c-di-AMP-associated genes of S. pneumoniae. The results showed that SPD_1392 (DacA) is a diadenylate cyclase that converts ATP to c-di-AMP. Both SPD_2032 (Pde1) and SPD_1153 (Pde2), which belong to the DHH subfamily 1 proteins, displayed c-di-AMP phosphodiesterase activity. Pde1 cleaved c-di-AMP into phosphoadenylyl adenosine (pApA), whereas Pde2 directly hydrolyzed c-di-AMP into AMP. Additionally, Pde2, but not Pde1, degraded pApA into AMP. Our results also demonstrated that both Pde1 and Pde2 played roles in bacterial growth, resistance to UV treatment, and virulence in a mouse pneumonia model. These results indicate that c-di-AMP homeostasis is essential for pneumococcal biology and disease. PMID:24013631

  15. 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.

  16. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-09-28

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The background image showing global sea surface circulation colored by temperature where reds are warm areas (32 degrees Celsius) and blues are cold regions (0 degrees Celsius). The data used for this visual is a joint MIT/JPL project called Estimating the Circulation and Climate of the Ocean, Phase II (ECCO2). For more info on this visual, svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=3912 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  17. Extraction of Palladium from Nitric Acid by Diamides of Di-picolinic Acid

    SciTech Connect

    Alyapyshev, M.Yu.; Babain, V.A.; Pokhitonov, Yu.A.; Esimantovskiy, V.M.

    2007-07-01

    The most complicated and urgent problem of atomic industry consists in the safe isolation and storage of radioactive wastes. The long-lived radionuclides presented in high-level liquid wastes (HLLW) pose a potential threat to environment for hundreds and thousands of years. One of the possible ways to reduce the danger of HLLW storages is concerned with treatment of HLLW intended to recovery of long-lived radionuclides and their partitioning into separate fractions. The separation of the most hazardous radionuclides (like transplutonium elements (TPE)) to the individual fraction of low volume leads to decrease of the total volume of HLLW and therefore to decrease of solidified waste storage costs. It should be noted that only in the case of reprocessing it can be possible to recover individual radionuclides (or their fractions) into separate flows with further special approach to each of them. Partitioning of different HLLW is under investigation in many countries now. Numerous processes for recovery of Cs, Sr, TPE and REE have been already developed and tested. At the same time partitioning is only the first step on the road to the following synthesis of materials providing the safe storage of long-lived radionuclides over many thousands of years. The metallic palladium contained in HLLW seems to be a promising material for producing of matrices for incorporation of radioactive wastes. Different methods for palladium recovery have been investigated: reductive precipitation, electrochemical precipitation, sorption and extraction. Of prime importance are extraction methods. Phosphine oxides, carbamoyl-phosphine oxides, crown-ethers, oximes, sulfides and some other compounds were proposed as extractants towards palladium from nitric acid media. It is reasonable to recover palladium into individual fraction during waste partitioning. Diamides of malonic, di-glycolic and pyridine-dicarboxylic (di-picolinic) acids are intensively investigated as extractants for HLLW

  18. PilZ Domain Protein FlgZ Mediates Cyclic Di-GMP-Dependent Swarming Motility Control in Pseudomonas aeruginosa

    PubMed Central

    Baker, Amy E.; Diepold, Andreas; Kuchma, Sherry L.; Scott, Jessie E.; Ha, Dae Gon; Orazi, Giulia

    2016-01-01

    ABSTRACT The second messenger cyclic diguanylate (c-di-GMP) is an important regulator of motility in many bacterial species. In Pseudomonas aeruginosa, elevated levels of c-di-GMP promote biofilm formation and repress flagellum-driven swarming motility. The rotation of P. aeruginosa's polar flagellum is controlled by two distinct stator complexes, MotAB, which cannot support swarming motility, and MotCD, which promotes swarming motility. Here we show that when c-di-GMP levels are elevated, swarming motility is repressed by the PilZ domain-containing protein FlgZ and by Pel polysaccharide production. We demonstrate that FlgZ interacts specifically with the motility-promoting stator protein MotC in a c-di-GMP-dependent manner and that a functional green fluorescent protein (GFP)-FlgZ fusion protein shows significantly reduced polar localization in a strain lacking the MotCD stator. Our results establish FlgZ as a c-di-GMP receptor affecting swarming motility by P. aeruginosa and support a model wherein c-di-GMP-bound FlgZ impedes motility via its interaction with the MotCD stator. IMPORTANCE The regulation of surface-associated motility plays an important role in bacterial surface colonization and biofilm formation. c-di-GMP signaling is a widespread means of controlling bacterial motility, and yet the mechanism whereby this signal controls surface-associated motility in P. aeruginosa remains poorly understood. Here we identify a PilZ domain-containing c-di-GMP effector protein that contributes to c-di-GMP-mediated repression of swarming motility by P. aeruginosa. We provide evidence that this effector, FlgZ, impacts swarming motility via its interactions with flagellar stator protein MotC. Thus, we propose a new mechanism for c-di-GMP-mediated regulation of motility for a bacterium with two flagellar stator sets, increasing our understanding of surface-associated behaviors, a key prerequisite to identifying ways to control the formation of biofilm communities. PMID

  19. Identification and molecular characterization of a cyclic-di-GMP effector protein, PlzA (BB0733): additional evidence for the existence of a functional cyclic-di-GMP regulatory network in the Lyme disease spirochete, Borrelia burgdorferi

    PubMed Central

    Freedman, John C.; Rogers, Elizabeth A.; Kostick, Jessica L.; Zhang, Hongming; Iyer, Radha; Schwartz, Ira; Marconi, Richard T.

    2010-01-01

    The Borrelia burgdorferi Rrp1 protein is a diguanylate cyclase that controls a regulon consisting of ~10% of the total genome. Because Rrp1 lacks a DNA-binding domain, its regulatory capability is most likely mediated through the production of bis-(3′–5′)-cyclic dimeric GMP (c-di-GMP). C-di-GMP binds to and activates the regulatory activity of proteins that harbor a PilZ domain. The occurrence of a PilZ domain within a protein is not in and of itself sufficient to convey c-di-GMP binding, as other structural aspects of the protein are important in the interaction. In this study, we have assessed the expression and c-di-GMP binding ability of the sole PilZ domain-containing protein of B. burgdorferi B31, PlzA. PlzA was determined to be upregulated by tick feeding and to be expressed during mammalian infection. The gene is highly conserved and present in all Borrelia species. Analyses of recombinant PlzA demonstrated its ability to bind c-di-GMP and site-directed mutagenesis revealed that this interaction is highly specific and dependent on Arg residues contained within the PilZ domain. In summary, this study is the first to identify a c-di-GMP effector molecule in a spirochete and provides additional evidence for the existence of a complete c-di-GMP regulatory network in the Lyme disease spirochete, B. burgdorferi. PMID:20030712

  20. 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

  1. 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

  2. Effects of di-n-butyl phthalate and di (2-ethylhexyl) phthalate on the growth, photosynthesis, and chlorophyll fluorescence of wheat seedlings.

    PubMed

    Gao, Minling; Qi, Yun; Song, Wenhua; Xu, Haoran

    2016-05-01

    Phthalates are commonly used man-made chemicals that can be released into soil, water, and the atmosphere. The potential toxicity of phthalates on wheat seedlings has not been well studied. To better understand the deleterious effects of di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) on wheat seedlings, their influences on the following were investigated: plant growth, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO2 concentration (Ci), chlorophyll content, initial fluorescence (F0), maximal photochemical efficiency (Fv/Fm), photochemical quenching (qP), non-photochemical quenching (qN), effective quantum yield of photosystem II (ΦPSII), and photosynthetic electron transport rate (ETR). Compared with the control, the growth indices (plant height, fresh and dry weights of shoots, fresh and dry weights of roots), Pn, Gs, Tr, Ci, chlorophyll content, Fv/Fm, qP, ΦPSII, and ETR decreased in the 5 μg mL(-1) and 10 μg mL(-1) DBP and DEHP treatments, whereas F0 and qN increased. When wheat seedlings were treated with 20 μg mL(-1) of DBP and DEHP, the growth indices, Pn, Gs, Tr, chlorophyll content, Fv/Fm, qP, qN, ΦPSII, and ETR decreased significantly, whereas Ci and F0 increased. A decrease in the Pn of wheat seedlings was mainly caused by stomatal limitation in the 5 μg mL(-1) and 10 μg mL(-1) DBP and DEHP treatments. However, stomatal and non-stomatal limitations may have caused the reduction in Pn in the 20 μg mL(-1) DBP and DEHP treatments. Notably, the noxious effect of DBP on the wheat seedlings was significantly greater than that of DEHP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Study on the interaction of Co (III) DiAmsar with serum albumins: spectroscopic and molecular docking methods.

    PubMed

    Farahani, Bahman Vasheghani; Bardajee, Ghasem Rezanejade; Rajabi, Farzaneh Hosseinpour; Hooshyar, Zari

    2015-01-25

    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.

  5. 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

  6. Gestational and lactational exposure to di-isobutyl phthalate via diet in maternal mice decreases testosterone levels in male offspring.

    PubMed

    Wang, Xiaoyang; Sheng, Nan; Cui, Ruina; Zhang, Hongxia; Wang, Jianshe; Dai, Jiayin

    2017-04-01

    Phthalates are a large family of ubiquitous environmental chemicals suspected of being endocrine disruptors, with exposure to these chemicals during prenatal and postnatal development possibly resulting in reproductive disorders. Di-isobutyl phthalate (DiBP) is widely used in consumer and industrial products, and although its exposure in the general population has increased in recent years, the mechanisms behind DiBP-induced reproductive disorders in male offspring remain unclear. Here, pregnant mice were exposed to 0 or 450 mg/kg bw/day DiBP via diet from gestation day (GD) 0 to GD21. Until postnatal day 21 (PD21), half of the exposed pups were also exposed to DiBP by lactation (TT), while the rest were not (TC). Half of each group were sacrificed on PD21, with the remaining mice fed a normal diet until PD80 (TCC and TTC, respectively). Reproductive toxicological parameters such as relative organ weights and testosterone levels were determined in male offspring on PD21 and PD80 and sperm quality was tested on PD80. Maternal exposure (pregnancy and lactation) led to decreased serum and testis testosterone concentrations, accompanied by decreased expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 family 11 subfamily A member 1 (CYP11A1) in PD21 pups and PD80 adults. Furthermore, the TTC group showed decreased epididymis sperm concentration and motility. Taken together, DiBP exposure in early life (prenatal and postnatal) impaired male reproductive function in later life, possibly by interfering with testosterone levels and CYP11A1, which might be a major steroidogenic enzyme targeted by DiBP or other phthalates.

  7. 4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses Inflammatory Responses Through TRPV1 Activation.

    PubMed

    Kim, Yiseul; Kim, Jung Tae; Park, Joonwoo; Son, Hee Jin; Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

    2017-10-01

    Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca(2+) levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC50  = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. PdeB, a cyclic Di-GMP-specific phosphodiesterase that regulates Shewanella oneidensis MR-1 motility and biofilm formation.

    PubMed

    Chao, Lily; Rakshe, Shauna; Leff, Maija; Spormann, Alfred M

    2013-09-01

    Shewanella oneidensis MR-1, a gammaproteobacterium with respiratory versatility, forms biofilms on mineral surfaces through a process controlled by the cyclic dinucleotide messenger c-di-GMP. Cellular concentrations of c-di-GMP are maintained by proteins containing GGDEF and EAL domains, which encode diguanylate cyclases for c-di-GMP synthesis and phosphodiesterases for c-di-GMP hydrolysis, respectively. The S. oneidensis MR-1 genome encodes several GGDEF and EAL domain proteins (50 and 31, respectively), with a significant fraction (∼10) predicted to be multidomain (e.g., GGDEF-EAL) enzymes containing an additional Per-Arnt-Sim (PAS) sensor domain. However, the biochemical activities and physiological functions of these multidomain enzymes remain largely unknown. Here, we present genetic and biochemical analyses of a predicted PAS-GGDEF-EAL domain-containing protein, SO0437, here named PdeB. A pdeB deletion mutant exhibited decreased swimming motility and increased biofilm formation under rich growth medium conditions, which was consistent with an increase in intracellular c-di-GMP. A mutation inactivating the EAL domain also produced similar swimming and biofilm phenotypes, indicating that the increase in c-di-GMP was likely due to a loss in phosphodiesterase activity. Therefore, we also examined the enzymatic activity of purified PdeB and found that the protein exhibited phosphodiesterase activity via the EAL domain. No diguanylate cyclase activity was observed. In addition to the motility and biofilm phenotypes, transcriptional profiling by DNA microarray analysis of biofilms of pdeB (in-frame deletion and EAL) mutant cells revealed that expression of genes involved in sulfate uptake and assimilation were repressed. Addition of sulfate to the growth medium resulted in significantly less motile pdeB mutants. Together, these results indicate a link between c-di-GMP metabolism, S. oneidensis MR-1 biofilm development, and sulfate uptake/assimilation.

  9. 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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. 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....

  11. 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....

  12. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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....

  13. 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

  14. E88, a new cyclic-di-GMP class I riboswitch aptamer from Clostridium tetani, has a similar fold to the prototypical class I riboswitch, Vc2, but differentially binds to c-di-GMP analogs.

    PubMed

    Luo, Yiling; Chen, Bin; Zhou, Jie; Sintim, Herman O; Dayie, T Kwaku

    2014-03-04

    C-di-GMP has emerged as a ubiquitous second messenger, which regulates the transition between sessile and motile lifestyles and virulence factor expression in many pathogenic bacteria using both RNA riboswitches and protein effectors. We recently showed that two additional class I c-di-GMP riboswitch aptamers (Ct-E88 and Cb-17B) bind c-di-GMP with nanomolar affinity, and that Ct-E88 RNA binds 2'-F-c-di-GMP 422 times less tightly than class I Vc2 RNA. Based on sequence comparison, it was concluded that the global folds of Ct-E88 and Vc2 RNAs were similar and that differences in ligand binding were probably due to differences in binding site architectures. Herein, we utilized EMSA, aptamer sensing spinach modules, SAXS and 1D NMR titration to study the conformational transitions of Ct-E88. We conclude that whereas the global folds of the bound states of Vc2 and Ct-E88 RNAs are similar, the unbound states are different and this could explain differences in ligand affinities between these class I c-di-GMP riboswitches.

  15. Combining DI-ESI–MS and NMR datasets for metabolic profiling

    PubMed Central

    Marshall, Darrell D.; Lei, Shulei; Worley, Bradley; Huang, Yuting; Garcia-Garcia, Aracely; Franco, Rodrigo; Dodds, Eric D.; Powers, Robert

    2014-01-01

    Metabolomics datasets are commonly acquired by either mass spectrometry (MS) or nuclear magnetic resonance spectroscopy (NMR), despite their fundamental complementarity. In fact, combining MS and NMR datasets greatly improves the coverage of the metabolome and enhances the accuracy of metabolite identification, providing a detailed and high-throughput analysis of metabolic changes due to disease, drug treatment, or a variety of other environmental stimuli. Ideally, a single metabolomics sample would be simultaneously used for both MS and NMR analyses, minimizing the potential for variability between the two datasets. This necessitates the optimization of sample preparation, data collection and data handling protocols to effectively integrate direct-infusion MS data with one-dimensional (1D) 1H NMR spectra. To achieve this goal, we report for the first time the optimization of (i) metabolomics sample preparation for dual analysis by NMR and MS, (ii) high throughput, positive-ion direct infusion electrospray ionization mass spectrometry (DI-ESI-MS) for the analysis of complex metabolite mixtures, and (iii) data handling protocols to simultaneously analyze DI-ESI-MS and 1D 1H NMR spectral data using multiblock bilinear factorizations, namely multiblock principal component analysis (MB-PCA) and multiblock partial least squares (MB-PLS). Finally, we demonstrate the combined use of backscaled loadings, accurate mass measurements and tandem MS experiments to identify metabolites significantly contributing to class separation in MB-PLS-DA scores. We show that integration of NMR and DI-ESI-MS datasets yields a substantial improvement in the analysis of neurotoxin involvement in dopaminergic cell death. PMID:25774104

  16. 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.

  17. Far Ultraviolet Spectroscopy of Old Novae. II. RR Pic, V533 Her, and DI Lac

    NASA Astrophysics Data System (ADS)

    Sion, Edward M.; Godon, Patrick; Jones, Liam

    2017-03-01

    The old novae V533 Her (Nova Her 1963), DI Lac (Nova Lac 1910), and RR Pic (Nova Pic 1891) are in (or near) their quiescent stage, following their nova explosions, and continue to accrete at a high rate in the aftermath of their explosions. They exhibit continua that are steeply rising into the FUV, as well as absorption lines and emission lines of uncertain origin. All three have Far Ultraviolet Spectroscopic Explorer (FUSE) spectra that offer not only higher spectral resolution but also wavelength coverage extending down to the Lyman Limit. For DI Lac, we have matched these FUSE spectra with existing archival International Ultraviolet Explorer spectral coverage to broaden the FUV wavelength coverage. We adopted the newly determined interstellar reddening corrections of Selvelli & Gilmozzi. The dereddened FUV spectra have been modeled with our grids of optically thick accretion disks and hot, NLTE white dwarf (WD) photospheres. The results of our modeling analysis indicate that the hot components in RR Pic and V533 Her are likely to be accretion disks with mass accretion rates of 10‑8 M ⊙ yr‑1 and 10‑9 M ⊙ yr‑1 respectively. However, the disk cannot produce the observed absorption lines. For the WD to be the source of the absorption lines in these two systems, it must be very hot, with a radius several times its expected size (because the WD in these systems is massive, it has a smaller radius). For DI Lac, we find the best fit to be a disk with \\dot{M}={10}-10 {M}ȯ {{yr}}-1 with a 30,000 K WD. Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer (FUSE). FUSE was operated for NASA by the Johns Hopkins University under NASA contract NAS5-32985.

  18. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

    PubMed Central

    Lopez-Rivera, E.; Liu, Y.P.; Verbitsky, M.; Anderson, B.R.; Capone, V.P.; Otto, E.A.; Yan, Z.; Mitrotti, A.; Martino, J.; Steers, N.J.; Fasel, D.A.; Vukojevic, K.; Deng, R.; Racedo, S.E.; Liu, Q.; Werth, M.; Westland, R.; Vivante, A.; Makar, G.S.; Bodria, M.; Sampson, M.G.; Gillies, C.E.; Vega-Warner, V.; Maiorana, M.; Petrey, D.S.; Honig, B.; Lozanovski, V.J.; Salomon, R.; Heidet, L.; Carpentier, W.; Gaillard, D.; Carrea, A.; Gesualdo, L.; Cusi, D.; Izzi, C.; Scolari, F.; van Wijk, J.A.E.; Arapovic, A.; Saraga-Babic, M.; Saraga, M.; Kunac, N.; Samii, A.; McDonald-McGinn, D.M.; Crowley, T.B.; Zackai, E.H.; Drozdz, D.; Miklaszewska, M.; Tkaczyk, M.; Sikora, P.; Szczepanska, M.; Mizerska-Wasiak, M.; Krzemien, G.; Szmigielska, A.; Zaniew, M.; Darlow, J.M.; Puri, P.; Barton, D.; Casolari, E.; Furth, S.L.; Warady, B.A.; Gucev, Z.; Hakonarson, H.; Flogelova, H.; Tasic, V.; Latos-Bielenska, A.; Materna-Kiryluk, A.; Allegri, L.; Wong, C.S.; Drummond, I.A.; D’Agati, V.; Imamoto, A.; Barasch, J.M.; Hildebrandt, F.; Kiryluk, K.; Lifton, R.P.; Morrow, B.E.; Jeanpierre, C.; Papaioannou, V.E.; Ghiggeri, G.M.; Gharavi, A.G.; Katsanis, N.; Sanna-Cherchi, S.

    2017-01-01

    BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.) PMID:28121514

  19. [Synthesis and spectral characteristics of novel di-schiff base derivatives incorporting oxadiazole ring].

    PubMed

    Chen, Tong-bin; Zhang, Xiong-lu; Fan, Xiao-lin; Li, Xun

    2008-12-01

    4-nitrobenzoic acid and hydraxine sulfate were cyclized with H3PO4/P2O5 to afford 2,5-bis(4-nitrophenyl)-1, 3,4-oxadiazole(1), then(1)was reduced to 2,5-bis(4-aminophenyl)-1,3,4-oxadiazole using Zn/CaCl2 as reduction reagent, and at last, a series of novel di-schiff base derivatives containing oxadiazole ring were obtained by the reaction of 2,5-bis(4-aminophenyl)-1, 3,4-oxadiazole with aromatic aldehydes (yield: 65%-81%). The structures of these compounds were confirmed by 1H NMR, FTIR and MS. Their UV-Vis spectra as well as fluorescence spectra were studied and the electrochemical properties were tested with cyclic voltammetry. The UV-Vis spectroscopy results show that the characteristic absorption peaks of 1, 3, 4-oxadiazole unit and di-schiff base unit disappeared. The maximum absorption wavelength was detected at 345-357 nm because conjugation effect made the two energy bands partially hybrid and form a new energy band structure. Fluorescence spectroscopy results show that they emit strong blue and purple fluorescence, and the emission maximum wavelengths of di-schiff base are from 390 to 407 nm. Electrochemical properties results show that they have higher affinity energy (2.36-3.04 eV) and ionic potential (5.35-6.06 eV), which indicated that they have better electron-transporting properties than PBD except 3 a and 3 h. The results give a reference to further application to organic electroluminescent devices of the target compound.

  20. 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.