WorldWideScience

Sample records for gli anelli del

  1. Literature in Focus - Gli anelli del sapere = The Rings of Knowledge + The LHC bible

    CERN Multimedia

    Tullio Basaglia

    2010-01-01

    A fascinating photographic survey describes the essential phases of constructing the colossal equipment to build the four main experiments. It is enriched by a sophisticated, experimental graphic design and the stories of the Italian scientists from the INFN (National Institute of Nuclear Physics), who made vital contributions to the project and constructing the LHC. The book is completed by descriptions illustrating the important contribution that Italian companies made to this major project, demonstrating Italy’s competitive capacity for excellence in the most important technological undertakings in Europe. Edited by Federico Brunetti (Politecnico di Milano) Published by Editrice Abitare Segesta The presentation of the book will take place on Tuesday, 9th March, 4.00 p.m. in the Pas Perdus area. At the same time, the INFN photo exhibition installed in the occasion of the International Women's day will also be inaugurated. A reception will be sponsored by the Permanent Mission of Italy to th...

  2. Come diventare una Rockstar. Gli Houser e l’evoluzione del franchise Grand Theft Auto.

    Directory of Open Access Journals (Sweden)

    Federico Giordano

    2013-03-01

    Full Text Available Wanted. La storia criminale di Grand Theft Auto, Multiplayer, 2012, il libro scritto da David Kushner, giornalista e docente universitario già autore del precedente, molto apprezzato, Master of Doom, è un testo importante per gli studi sui videogiochi, nonostante non si presenti in apparenza – a partire dal titolo evocativo – come testo accademico.

  3. Note sulla concezione del post mortem presso gli Ittiti

    DEFF Research Database (Denmark)

    Vigo, Matteo; Bellucci, Benedetta

    significato escatologico della morte; 2) la definizione dello status ultraterreno dei defunti (i.e. il diverso trattamento del defunto, ad esempio dal punto di vista cultuale, sulla base della sua condizione sociale); 3) il delineamento dei caratteri e delle funzioni delle divinità ultra-terrene; 4) la......Oggetto d’analisi di questo paper è la concezione della sfera del post-mortem presso la civiltà degli Ittiti. Lo studio delle tematiche che riguardano la concezione dell’“aldilà” nel mondo ittita, sia in senso fisico che metafisico, riveste una larga importanza nella letteratura ittitologica ed è...... stato, pertanto, diffusamente trattato. Nel presente contributo si è scelto quindi di approfondire solo alcuni aspetti della concezione dell’oltretomba, inteso come dimensione metafisica in cui il corpo del defunto giace, staziona o transita dopo la morte. I temi approfonditi saranno quindi: 1) il...

  4. L’arcipelago postmoderno. Oreste del Buono e gli anni Settanta

    Directory of Open Access Journals (Sweden)

    Andrea Chiurato

    2012-12-01

    Il tentativo di cooptazione postuma tra le file dei simpatizzanti da parte del Gruppo 63 avrà breve fortuna (verrà incluso nella prima antologia del gruppo, ma non nelle se-guenti, e Renato Barilli arriverà addirittura a porlo a capo di un improbabile «Polo Bu-tor» (Chiurato 14, uno sparuto gruppo di „infiltrati‟ (insieme a Raffaele La Capria, Emilio Tadini, e Giuliano Gramigna nelle file della compagine neoavanguardista. Quarant‟anni dopo la questione rimane aperta e l‟eredità di quel turbolento periodo è ancora oggetto di discussione. La nostra intenzione è proporre un approccio diverso, che cer-chi di restituire la fluidità e la ricchezza delle suggestioni di allora poi irrigiditesi in cate-gorie critiche spesso frutto di semplificazioni indebite. Del Buono, irriducibile outsider, ci permette così di riscoprire gli anni Settanta da un‟angolazione inedita e di colmare, nello stesso tempo, alcune improvvide lacune nella nostra memoria culturale

  5. Il degrado abusivo e il "degrado legale" del territorio: gli ecomostri

    Directory of Open Access Journals (Sweden)

    Anna Cicchetti

    2010-07-01

    Full Text Available Il fenomeno di una urbanizzazione senza criteri né misure, collegata a ragioni turistiche, molto spesso opportunistiche, è affrontato dalla giurisprudenza nella sua azione di controllo del territorio: ne sono un caso esemplare gli “ecomostri”, ormai comunemente e tristemente sono conosciuti dalla società civile. Queste costruzioni di grande impatto territoriale, ambientale e paesaggistico, in alcuni casi sono legittimati da interventi normativi non bene soppesati e in altri avvengono in maniera c.d. abusiva, con l’unica conseguenza, in entrambe le ipotesi, di deturpare l’ambiente circostante sotto molteplici profili, non ultimo quello incidente su località turistiche. Il contributo si pone l’obiettivo di contribuire ad una politica turistica attenta al profilo ambientale: occorre individuare una maggiore cogenza e conoscenza normativa a favore di una pianificazione urbanistica e politica del paesaggio, in grado di sostenere il recupero, la riqualificazione e valorizzazione delle bellezze naturali presenti sul territorio. Solo il coinvolgimento e la necessaria collaborazione di tutti i soggetti del territorio per una programmazione orientata a realizzare uno «sviluppo capace di rispondere ai bisogni delle generazioni attuali, senza compromettere la capacità delle generazioni future di rispondere ai propri».

  6. Le maschere senza volto. Gli eroi “tragici” del nouveau roman

    Directory of Open Access Journals (Sweden)

    Andrea Chiurato

    2017-11-01

    Full Text Available Tra i vari movimenti sperimentali affermatisi nel corso del secondo Novecento il nouveau roman offre un’occasione quanto mai preziosa a chi volesse riconsiderare il mutevole valore e le innumerevoli funzioni attribuite al “tragico” alle soglie dell’era postmoderna. Posta al centro del dibattito critico da Alain Robbe-Grillet, la riflessione sull’ambiguo statuto di questo peculiare genere ha d’altronde rappresentato un momento cruciale nella definizione dell’identità dell’école du regard e del suo peculiare rapporto con la tradizione del canone occidentale. Robbe-Grillet, dal canto suo, pur ispirandosi alla vicenda di Edipo nella sua opera d’esordio, non esiterà in seguito a condannare la tragedia come ingannevole forma di compromesso tra l’uomo e le choses e a rifiutare, insieme a essa, la “metafisica della presenza” di cui sarebbe espressione. Altri nouveaux romanciers – tra cui Michel Butor – preferiranno invece sfruttarne le potenzialità in maniera inedita, ritenendola uno sfondo mitopoietico ideale su cui far emergere i tratti essenziali di una condizione esistenziale all’insegna del crollo delle grandi narrazioni. Al di là delle diverse intenzioni, la rivisitazione della “forma” in sé (in chiave parodica o attualizzante ha di conseguenza svolto un ruolo cruciale sia nella decostruzione del “personaggio-uomo”, sia nella contestazione delle cosiddette “nozioni scadute” tanto indigeste a questa eterogenea collection d’écrivains. Da Les gommes (1953 a L’emploi du temps (1956, per arrivare sino a Sphinx en chapeau (1984, si potrebbero menzionare numerosi esempi a tal riguardo, segno di una fascinazione costante, ma non per questo meno conflittuale, destinata a esercitare una profonda influenza su alcuni dei maggiori dei successi editoriali dello sperimentalismo francese. Un’influenza di cui oggi, ormai esauritisi gli accesi toni dello scandalo e della provocazione che accompagnarono l

  7. Gli incerti confini del cosmo dai buchi neri alle macchine del tempo

    CERN Document Server

    De Felice, Fernando

    2000-01-01

    Il libro mostra come la gravitazione abbia un ruolo determinante nei fenomeni cosmici che più ci impressionano, da quelli relativamente vicini alla nostra esperienza (come la formazione delle stelle) a quelli meno intuibili (come la formazione dei buchi neri), alla struttura dell'Universo nel suo insieme. Oltre a spiegare, in modo qualitativo, concetti come la geometria dello spazio-tempo, la relatività del tempo e i coni di luce, l'autore formula un'ipotesi innovativa tendente a spiegare l'origine della gravitazione e con essa quella dei fenomeni circondati ancora da un alone di mistero: la materia oscura dell'Universo e il destino della materia alla fine del collasso gravitazionale.

  8. The Bridge Impacts: Unsustainable Undergrowth Gli impatti del Ponte: sottosviluppo insostenibile

    Directory of Open Access Journals (Sweden)

    Alberto Ziparo

    2011-11-01

    " contenuta nel progetto '80, alle posizioni critiche che, rispetto a tali concetti, sono maturate negli studi relativi alle più recenti versioni del progetto. Nella seconda parte si descrivono gli elementi principali del "progetto di attraversamento aereo dello Stretto di Messina" presentato dalla società dello Stretto al governo il 31/12/02 (progetto preliminare, che ha registrato il parere positivo con prescrizioni del CIPE nel 2005, di cui è stata di recente presentata la versione “definitiva”; e ancora note tratte dalle "Osservazioni sullo studio di impatto ambientale", avanzate per conto di Legambiente, WWF, Italia Nostra e di altre associazioni ambientaliste, da un gruppo di studio coordinato dall'autore delle note presenti, riassumendo anche recenti lavori di aggiornamento (Bettini, Guerzoni, Ziparo, 2002; Pieroni, 2000; Pieroni, Ziparo, 2010; Marino, 2011.

  9. Gli effetti socio-economici e spaziali del servizio ferroviario dell’Alta Velocità: due casi a confronto

    Directory of Open Access Journals (Sweden)

    Loredana Consuelo Travascio

    2008-05-01

    Full Text Available L’articolo fornisce una lettura degli effetti socio-economici e spaziali generati dalla messa in esercizio di una rete ferroviaria ad AV sull’organizzazione territoriale. Esso si articola in due parti. Nella prima, sono analizzati gli effetti che in letteratura sono attribuiti alle infrastrutture di trasporto, focalizzandosi sulle ripercussioni che la messa in esercizio dell’AV ha generato sulla crescita demografica e sulla localizzazione delle attività economiche attorno alle stazioni, nonché sulla domanda di trasporto e sulla riconfigurazione dei flussi. Nella seconda parte si passa allo studio di due casi significativi: il Giappone, dove l’introduzione del servizio ha modificato la struttura socio-economica del territorio; la Spagna, dove ha favorito la comparsa di nuove tipologie di utenti e la ridefinizione delle relazioni tra le varie città servite dall’infrastruttura.

  10. Gli affari di messer Palla Strozzi (e di suo padre Nofri. Imprenditoria e mecenatismo nella Firenze del primo Rinascimento

    Directory of Open Access Journals (Sweden)

    Sergio Tognetti

    2011-10-01

    Full Text Available Il saggio si propone di far luce sulle vicende economico-patrimoniali di messer Palla di Nofri Strozzi (Firenze 1372-Padova 1462, personaggio di spicco della Firenze del primo Rinascimento, sia come uomo politico ingiustamente travolto dalla purga medicea scatenata nel 1434 contro gli oppositori di Cosimo il Vecchio, sia come letterato, collezionista di codici librari, promotore degli studia humanitatis e committente di opere d’arte. Al centro di una frammentata serie di indagini da parte di storici dell’arte, della cultura e della politica, Palla Strozzi ha suscitato invece scarsa attenzione da parte degli storici dell’economia, nonostante un particolare non secondario: al catasto fiorentino del 1427 risultava essere il cittadino più ricco, ma dopo nemmeno cinque anni era già così oberato dai debiti da non riuscire più a pagare le tasse al fisco fiorentino. La vicenda di messer Palla, messa a confronto con quella del padre Nofri, infaticabile uomo d’affari capace di ammassare una gigantesca fortuna (poi parzialmente dissipata dal figlio, è analizzata nei dettagli grazie alla ricchissima serie archivistica delle carte strozziane: in particolare tramite lo spoglio di numerosi libri di conti intestati ad aziende e patrimoni di famiglia. Il confronto tra le differenti attitudini dei due personaggi fa emergere in tutta la sua originalità la figura di messer Palla: uomo coltissimo ma anche elitario, eppure dotato di un alto senso dello stato, capace di mostrare verso il denaro un’inclinazione che lo avvicina più all’aristocratico rentier dell’ancien régime e/o al raffinato signore padano del pieno rinascimento, piuttosto che al mondo dei grandi «mercatanti» che lo aveva generato.

  11. Gli spazi marginali di un personaggio bizzarro: l’adattamento del romanzo Totò il buono

    Directory of Open Access Journals (Sweden)

    Matteo Martelli

    2012-11-01

    Full Text Available Il saggio propone uno studio del romanzo di Cesare Zavattini, Totò il buono, e della riscrittura filmica Miracolo a Milano (firmata da Zavattini stesso e Vittorio De Sica attraverso l’analisi della figura del protagonista, Totò, personaggio eccentrico e buono. In maniera particolare, a partire dalla presenza in entrambi i testi di spazi di marginalità culturale dai quali si costruiscono le qualità bizzarre del personaggio, il saggio descrive come il lavoro d’adattamento rielabori le formulazioni del romanzo attraverso l’introduzione di un punto di vista della tradizione, estetica e antropologica, del grottesco e del realismo popolare, integrando e spostando al tempo stesso il precedente stato di marginalità da uno spazio asociale alla valorizzazione, sul piano immaginario, di un’utopia comunitaria.

  12. Gli atomi di Boltzmann

    CERN Document Server

    Lindley, David

    2002-01-01

    Ludwig Boltzmann (1844-1906) è il fisico e matematico austriaco che negli ultimi decenni dell'Ottocento e ancora ai primi del Novecento lottò contro l'opinione dominante tra gli scienziati dell'epoca per affermare la teoria atomica della materia. È noto come con Albert Einstein e fino a oggi la fisica si sia sviluppata e abbia celebrato i propri trionfi lungo le linee anticipate da Boltzmann. La controversia con Mach non riguardava soltanto l'esistenza degli atomi, ma l'intero modo di fare fisica che Boltzmann non riteneva di dover limitare allo studio di quantità misurabili, introducendo invece spiegazioni più elaborate basate su ipotesi più ampie.

  13. Variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no se asocian a la diabetes mellitus tipo 2 en un grupo de la población cubana The Ala513Pro and Gly972ARg polymorphous variants of IRS-1 gen are not associated with type diabetes mellitus in a group of the Cuban population

    Directory of Open Access Journals (Sweden)

    Luis Miguel Pérez

    2011-08-01

    Full Text Available Introducción: la diabetes mellitus tipo 2 es una enfermedad heterogénea y multifactorial, que está determinada por factores genéticos y no genéticos. El sustrato 1 del receptor de la insulina (IRS-1 cumple una función fundamental en la transmisión de la señal insulínica, por tanto sus variantes génicas constituyen blancos importantes en el estudio de la susceptibilidad genética a esta enfermedad en las diferentes poblaciones. Objetivo: explorar el papel de las variantes polimórficas Gly972Arg y Ala513Pro del gen IRS-1 en la susceptibilidad genética de la diabetes mellitus tipo 2 en un grupo de la población cubana. Métodos: se determinó la frecuencia de los polimorfismos Gly972Arg y Ala513Pro del IRS-1 en 499 ciudadanos cubanos, con un índice de masa corporal entre 22-30, con edades comprendidas entre los 40 y 70 años: de ellos 272 (54,5 % diabéticos y 227 (45,5 % no diabéticos. Resultados: la frecuencia del alelo Pro513 fue baja (1,2 % y similar para ambos grupos (1,1 % vs. 1,3 % para el grupo de diabéticos y el grupo control, respectivamente. La frecuencia del polimorfismo Gly972Arg fue de 16,2%, superior a la reportada para la mayoría de las poblaciones estudiadas. No se encontraron diferencias significativas en la frecuencia del alelo Arg972 entre el grupo de diabéticos y el grupo control (15,4 % vs. 17,3 %, ni cambios en los niveles de glucemia e insulinemia asociados a la presencia del alelo polimórfico Arg972. Conclusiones: en este grupo de sujetos de la población cubana, las variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no participan en la etiología de la diabetes mellitus tipo 2.Introduction: the type 2 diabetes mellitus is a heterogeneous and multifactor disease determined by genetic and no-genetic factors. The substrate 1 of insulin receptor (IRS-1 has a fundamental function in transmission of insulin signal, thus its genic variants are significant targets in study of genetic susceptibility to

  14. Gli uccelli del Parco Nazionale della Val Grande e delle aree limitrofe (Verbano Cusio Ossola, Piemonte, Italia

    Directory of Open Access Journals (Sweden)

    Fabio Casale

    2014-12-01

    Full Text Available Il Parco Nazionale della Val Grande è un’area montuosa protetta sita nelle Alpi, nel Piemonte nord-orientale, Italia. L’area è stata designata quale Parco Nazionale nonché ZPS – Zona di Protezione Speciale secondo la Direttiva “Uccelli” e IBA – Important Bird Area secondo BirdLife International. L’area di studio ha una superficie di 45.873 ha che comprende il Parco Nazionale e le limitrofe Valle Intrasca, Valle Cannobina e Val Loana, i cui ambienti principali sono costituiti da vaste foreste di latifoglie e di conifere, ambienti rocciosi, brughiere, arbusteti e praterie alpine. Le cime più alte raggiungono i 2.300 m s.l.m. La maggior parte della sua superficie è selvaggia e disabitata. In questo lavoro viene riportato un elenco commentato degli uccelli noti per l’area e vengono inoltre forniti dati di sintesi relativi alle attività di monitoraggio condotte in anni recenti (2009-2014. I dati sono stati raccolti sia attraverso revisione bibliografica sia in forma originale, attraverso attività di ricerca sul campo. Queste ultime sono state condotte utilizzando i seguenti metodi: mappaggio dei territori (uccelli nidificanti degli ambienti aperti, punti d’ascolto (uccelli nidificanti, transetti lineari con uso di playback (rapaci notturni, Caprimulgus europaeus, Dryocopus martius, ricerca di campo non standardizzata in ambienti idonei alla nidificazione (Passeriformi nidificanti degli ambienti rocciosi, censimento primaverile di rapaci migratori lungo la rotta migratoria del Lago Maggiore e censimento autunnale di Passeriformi migratori attraverso i passi alpini. L’area ospita o ha ospitato 138 specie di Uccelli delle quali 97 nidificanti, 28 di interesse comunitario (Allegato I della Direttiva “Uccelli”, 42 SPEC - Species of European Conservation Concern secondo BirdLife International. L’area è di grande importanza per numerose specie di uccelli, specialmente per la nidificazione di specie di interesse

  15. Radiation-induced chemical evolution of glycine to (Gly)2, (Gly)3, and (Gly)4

    International Nuclear Information System (INIS)

    Matsui, T.; Izumi, Y.; Kamohara, M.; Nakagawa, K.; Yokoya, A.

    2006-01-01

    Recently amino acids were detected from some meteorites. Since these amino acids were found after hydrolysis, some oligopeptides were possibly formed in space. A simulation experiment of chemical evolution from Glycine (Gly) to Glycylglycine ((Gly)2) was reported by Kaneko et al. In this work, we irradiated (Gly)2 with 8 eV vacuum ultraviolet photons or with 530 eV soft X-ray photons and examined absolute values of quantum yield of radiation-induced chemical evolution from Gly2 to Glycylglycylglycine ((Gly)3) and Glycylglycylglycylglycine ((Gly)4). Thin films of (Gly)2 were prepared on quartz plate or CuBe plate with a vacuum evaporation technique. These samples were irradiated by 8 eV photons from a Xe 2 * excimer lamp or by 530 eV soft X-ray photons at SPring-8 Synchrotron Radiation Facility. Irradiated samples were analyzed with a high performance liquid chromatography HPLC. Decomposition of (Gly)2 and production of Gly, (Gly)3 and (Gly)4 were observed. Quantum yield Y was defined to be N = Y N 0 , where N is the number of produced or decomposed molecule, and N 0 is the number of (Gly)2 molecules excited by photons. Obtained results by 8 eV irradiation were summarized in Table 1. The similar magnitude of decomposition of (Gly)2 may show that yield of the primary breaking reaction upon photo-excitation is of similar magnitude. It should be noted that (Gly)3 and (Gly)4 was produced by irradiation with the yield of 10 -4 without any catalysis. For soft X-ray irradiation, yield of Gly was tentatively determined to be about 40. This largervalue than that for 8 eV irradiation may originate from large energy of incident soft X-ray photons just like a result reported by Simakov et al. We will discuss in detail at the conference. (authors)

  16. Ask the users, il valore aggiunto della valutazione dei sistemi informativi culturali on line coinvolgendo gli utenti: il caso del progetto “Una Città per gli Archivi” / Ask the users, the added value of the evaluation of on-line cultural information systems involving users: the case of “Una città per gli archvi” project

    Directory of Open Access Journals (Sweden)

    Pierluigi Feliciati

    2012-10-01

    Digital environments aimed at offering services on historical records and documents put together archival domain standards with the typical features of digital libraries, with item-level descriptions, access to digital objects, subject-based searching. How can on line archives move from the plain delivery of structured information to the facilitation of a cultural experience? This communication presents some of these issues, with a focus on the peculiarities of web displays for archival descriptions and reproductions. In this field, the role played by user studies is crucial, to guarantee that return on investment whose first profit should be users satisfaction. After a short review of the international state of the art the author will present an on-going user study project, launched to test the prototype of Una Città per gli Archivi, the web portal disseminating the results of a huge project of preservation and valorization of documentary funds of the city of Bologna, including photographic and graphic materials, sound and audiovisual recordings, in addition to paper archives.

  17. Lorenzo Lotto e gli strumenti del mestiere: la periferia come consapevole scelta strategica / Lorenzo Lotto and the tools of the trade: the periphery as a conscious strategic choice

    Directory of Open Access Journals (Sweden)

    David Frapiccini

    2014-06-01

    Full Text Available Con il testamento del 25 marzo 1531 Lorenzo Lotto stabiliva la ripartizione dei modelli in gesso e in cera e dei propri disegni tra tre suoi antichi allievi: il bergamasco Francesco Bonetti, il veneziano Pietro di Giovanni – in quel momento attivo a Ragusa, l’odierna Dubrovnik – e il marchigiano maestro Giulio da Amandola, identificabile con Giulio Vergari. Dalle provenienze dei tre artefici si manifesta una chiara mappa geografica, come se Lotto avesse consapevolmente deciso di lasciare i ferri del mestiere nei luoghi della sua esperienza pittorica: a Bergamo, a Venezia e nelle Marche. Contemporaneamente Lotto frequenta i pittori Alessandro Oliverio, Bonifacio de’ Pitati da Verona e Girolamo da Santa Croce: il secondo, stando alle disposizioni testamentarie, avrebbe dovuto completare le opere rimaste incompiute alla morte di Lotto, mentre al terzo sarebbero andati alcuni strumenti della professione a beneficio dei propri figli. Si viene così a delineare un gruppo di artisti marginale rispetto al contesto lagunare, ma orientato verso committenze di entroterra o di area adriatica. La consapevolezza acquisita da Lotto nell’incidenza territoriale della sua attività spiega la ragione delle reminiscenze iconografiche e formali bergamasche in parte della produzione risalente agli estremi anni marchigiani (1549-1556, ovvero a quella fase inaugurata con l’Assunzione anconetana di San Francesco alle Scale, pala realizzata nel 1549-1550 con la collaborazione di Giuseppe Belli da Ponteranica. With the will of March 25, 1531 Lorenzo Lotto established the distribution of models in plaster and wax and their designs to three of his former pupils: Francesco Bonetti from Bergamo, the Venetian Pietro di Giovanni – at that time active in Ragusa, today's Dubrovnik – and maestro Giulio from Amandola identified with Giulio Vergari. The origins of the three painters manifest a clear geographical map, as if Lotto had consciously decided to leave the

  18. Evaluation of the oxidative stress modulation in Drosophila melanogaster strains deficient in endogenous antioxidants and with chronic exposure to casiopeina Cas II-gly and gamma radiation; Evaluacion de la modulacion del estres oxidante en cepas de Drosophila melanogaster deficientes en antioxidantes endogenos y con exposicion cronica a casiopeina CII-gly y radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez V, E. R.

    2013-07-01

    The casiopeinas are a family of coordination compounds with copper metallic center that have shown to have antineoplastic activity. The experimental evidences suggest that its action mechanism is through the generation of free radicals. The casiopeina (Cas II-gly) is believed to causes oxidative damage in the mitochondria, leading to the cellular death. The present study has the purpose to evaluate the antioxidant potential of the tetrapyrroles: cupro-sodica chlorophyllin (CSC), protoporphyrin-Ix (Pp-Ix) and the bilirubin (Bili) against the oxidant action of the Cas II-gly. The present study will also contribute in the characterization of the biological activity of the Cas II-gly. For this purpose is quantifies the effect of these compounds in the enzymes activity, superoxide dismutase (Sod) and catalase (Cat) in wild Drosophila melanogaster strains Canton-S and in the deficient in Sod and Cat. Two protocols were used, in the first male of 1-24 h of age were pre-treated with 0, 0.01, 0.1 and 1 m M of Cas II-gly and later on they were treated with radiation (15 Gy), and the second 69 m M of CSC, Pp-Ix or Bili, during 8 days and later they were treated with 0.1 m M of Cas II-gly during 24 h. The enzymatic activity was measured with the detection packages of enzymes Sod and Cat of Sigma. It was found that none of the three pigments increment the Sod activity but, if they diminished that of Cat (p≤0.007). The three concentrations of Cas II-gly did not increase the Sod activity significantly, only the concentration of 0.1 m M diminishes in 5.6 U the Cat activity (p <0.03) the same as the treatment with 15 Gy of gamma rays (8 U, p <0.004). The Cas II-gly combination 0.1 m M with the pigments does not modify the Sod and Cat activity. These results suggest that the proven pigments act as antioxidants, avoiding the induction of exogenous antioxidants caused by the gamma rays or the Cas II-gly. (Author)

  19. Surface-enhanced Raman spectrum of Gly-Gly adsorbed on the silver colloidal surface

    Science.gov (United States)

    Xiaojuan, Yuan; Huaimin, Gu; Jiwei, Wu

    2010-08-01

    Raman and SERS spectra of homodipeptide Gly-Gly and Gly were recorded and compared in this paper, and band assignment for the functional groups contained in these molecules was analyzed in detail. Time-dependent and pH-dependent SERS spectra of Gly-Gly molecule adsorbed on nano-colloidal silver surface were also studied. The time-dependent SERS spectra of Gly-Gly are characterized by the increase in intensity of bands primarily representing the vibrational signatures emanating from the amino and amide moiety of Gly-Gly molecule. It is found that the adsorption style of Gly-Gly on the silver colloid changes as time goes on; at 5 min after adding the sample to the silver colloid, Gly-Gly adsorbs on silver surface firstly through the carboxylate, amino and amide groups, and then the carboxylate group is far away from the silver surface at 10 min to 3 days. The SERS variation of Gly-Gly with the change of pH suggests that the adsorption style is pH-dependent, the different adsorption behavior of the Gly-Gly occurs on silver surface at different pH values.

  20. Domestic allergens; Gli allergeni domestici

    Energy Technology Data Exchange (ETDEWEB)

    Bressa, G. [Padua Univ., Padua (Italy). DIpt. di Tossicologia Ambientale

    2000-12-01

    Closed rooms can be the ideal habitat for the growth of many micro-organisms, some of which pathogenic for man. Indoor biologic contamination sources can vary: 1) external air can, through dust particles or water droplets, transfer a large number of germs inside the house; 2) air conditioning plants can become, if maintenance isn't carried out at regular intervals, a cultural medium for microbes which later spread to the air of house or office; 3) the presence of sick people or healthy carriers of pathogenic germs in closed rooms can represent a significant source of biologic contamination; 4) lastly, pets too can be considered as disease carriers. Particularly interesting is the so-called biologic dust - where mites proliferate - which, being trapped in curtains, carpeting, tapestry, fabrics and carpets, often causes respiratory system diseases. [Italian] Gli ambienti chiusi possono costituire l'habita ideale per la crescita di molti microorganismi, alcuni dei quali patogeni per l'uomo. Le fonti di contaminaizone biologica indoor possono essere diverse: 1) l'aria esterna puo' trasferire all'interno, attraverso particelle di polvere o goccioline d'acqua, un gran numero di germi; 2) gli impianti di condizionamento possono divenire, quando non si effettua una corretta manutenzione periodica, terreno di coltura di microbi che successivamente si diffondono nell'aria dell'abitazione o dell'ufficio; 3) la presenza in locali chiusi di persone malate o portatrici sane di germi patogeni puo' costituire un'importante sorgente di contaminazione biologica; 4) infine anche gli animali domestici possono essere considerati vettori di malattie. Di particolare interesse sono le polveri cosidette biologiche, in cui proliferano gli acari, che, essendo trattenute da tendaggi, parati, moquette, tessuti e tappeti, provocano frequentemente malattie dell'apparato respiratorio.

  1. Gli studi di Enrico Cerulli su Dante

    Directory of Open Access Journals (Sweden)

    Andrea Celli

    2013-12-01

    Full Text Available Nel 1949 lo studioso di lingue semitiche Enrico Cerulli pubblicò un volume, intitolato Il “Libro della scala” e la questione delle fonti arabo-spagnole della Divina Commedia, che segnò gli studi danteschi, per lo meno per quanto riguarda il dibattito sulle fonti arabo-islamiche del medioevo europeo. Le ricerche di Cerulli su Dante si presentavano come una analisi di fatti di trasmissione culturale. Ma l’autore si era già affermato, nella prima parte della sua carriera, in un più controverso ambito di competenze: alto funzionario dell’amministrazione coloniale italiana e vice-governatore dell’Africa Orientale Italiana, è stato rilevante studioso di lingue del Corno d’Africa, cioè le lingue delle colonie italiane. Questo saggio vuole connettere gli studi danteschi di Cerulli alle responsabilità coloniali e post-coloniali dell’autore, attraverso la ricostruzione della sua biografia intellettuale. Difatti, da queste ricerche Cerulli ricavò il concetto di unità della civiltà mediterranea, formula di evidente valore politico in rapporto all’Italia del secondo dopoguerra. Il saggio prova a offrire anche uno stato dell’arte del dibattito attuale sulle fonti arabe di Dante.  In 1949, Enrico Cerulli, an Italian scholar of Ethiopic-Semitic languages, published a volume entitled The “Book of the Ladder” and the Problem of Divine Comedy’s Arabic-Spanish Sources, which was to become a landmark in the discussion on the knowledge held by medieval Europe of Arabic-Islamic culture. His investigation was an analysis of cases of cultural transmission. However, Cerulli had established himself during the first half of his career in a more controversial domain: he was a senior official of Italian colonial administration and he was already well known as an expert of Italian colonies’ languages and traditions. This essay, through a survey of Cerulli’s intellectual biography, aims to bridge his research on Dante and his involvement

  2. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Roberta eHaddad-Tóvolli

    2015-03-01

    Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

  3. Secondary Structure Adopted by the Gly-Gly-X Repetitive Regions of Dragline Spider Silk

    Directory of Open Access Journals (Sweden)

    Geoffrey M. Gray

    2016-12-01

    Full Text Available Solid-state NMR and molecular dynamics (MD simulations are presented to help elucidate the molecular secondary structure of poly(Gly-Gly-X, which is one of the most common structural repetitive motifs found in orb-weaving dragline spider silk proteins. The combination of NMR and computational experiments provides insight into the molecular secondary structure of poly(Gly-Gly-X segments and provides further support that these regions are disordered and primarily non-β-sheet. Furthermore, the combination of NMR and MD simulations illustrate the possibility for several secondary structural elements in the poly(Gly-Gly-X regions of dragline silks, including β-turns, 310-helicies, and coil structures with a negligible population of α-helix observed.

  4. Role of GLI2 in hypopituitarism phenotype.

    Science.gov (United States)

    Arnhold, Ivo J P; França, Marcela M; Carvalho, Luciani R; Mendonca, Berenice B; Jorge, Alexander A L

    2015-06-01

    GLI2 is a zinc-finger transcription factor involved in the Sonic Hedgehog pathway. Gli2 mutant mice have hypoplastic anterior and absent posterior pituitary glands. We reviewed the literature for patients with hypopituitarism and alterations in GLI2. Twenty-five patients (16 families) had heterozygous truncating mutations, and the phenotype frequently included GH deficiency, a small anterior pituitary lobe and an ectopic/undescended posterior pituitary lobe on magnetic resonance imaging and postaxial polydactyly. The inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. The mutation was frequently inherited from an asymptomatic parent. Eleven patients had heterozygous non-synonymous GLI2 variants that were classified as variants of unknown significance, because they were either absent from or had a frequency lower than 0.001 in the databases. In these patients, the posterior pituitary was also ectopic, but none had polydactyly. A third group of variants found in patients with hypopituitarism were considered benign because their frequency was ≥ 0.001 in the databases. GLI2 is a large and polymorphic gene, and sequencing may identify variants whose interpretation may be difficult. Incomplete penetrance implies in the participation of other genetic and/or environmental factors. An interaction between Gli2 mutations and prenatal ethanol exposure has been demonstrated in mice dysmorphology. In conclusion, a relatively high frequency of GLI2 mutations and variants were identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with combined pituitary hormone deficiency and an ectopic posterior pituitary lobe. Future studies may clarify the relative role and frequency of GLI2 alterations in the aetiology of hypopituitarism. © 2015 Society for Endocrinology.

  5. Dimer of the peptide cycle (Ar-Gly-Asp-D-Phe-Lys) radiolabeled with {sup 99m}Tc for the integrin s over-expression image: formulation, biokinetics and dosimetry; Dimero del peptido ciclo(Arg-Gly-Asp-D-Phe-Lys) radiomarcado con {sup 99m}Tc para la imagen de sobre-expresion de integrinas: formulacion, biocinetica y dosimetria

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz A, Z.

    2013-07-01

    In breast cancer, α(v)β(3) and/or α(v)β(5) integrin s are over-expressed in both endothelial and tumour cells. Radiolabeled peptides based on the RGD (Arg-Gly-Asp) sequence are radiopharmaceuticals with high affinity and selectivity for those integrin s. The RGD-dimer peptide (E-[c(RGDfK)]{sub 2}) radiolabeled with {sup 99m}Tc has been reported as a radiopharmaceutical with 10-fold higher affinity for the α(v)β(3) integrin as compared to the RGD-monomer. EDDA (Ethylenediamine-N,N-diacetic acid) is a hydrophilic molecule that may favours renal excretion when used as coligand in the {sup 99m}Tc labelling of HYNIC-peptides and can easily be formulated in a lyophilized kit. Aim: Establish a biokinetic model for {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2} prepared from lyophilized kits and evaluate the dosimetry as breast cancer imaging agent. Methods: {sup 99m}Tc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer ph 7.0 to a lyophilized formulation containing E-[c(RGDfK)]{sub 2}, EDDA, tricine, mannitol and stannous chloride. Radiochemical purity was evaluated by reversed phase HPLC and ITLC-SG analyses. Stability studies in human serum were carried out by size-exclusion HPLC. In-vitro cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in MCF7 tumour-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from seven healthy women were acquired at 1, 3, 6 and 24 h after {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2} administration obtained with radiochemical purities of >94 %. Regions of interest (ROIs) were drawn around source organs on each time frame. Each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2} time-activity curves in each

  6. Radiation Chemical Studies of Gly-Met-Gly in Aqueous Solution

    NARCIS (Netherlands)

    Barata-Vallejo, Sebastian; Ferreri, Carla; Zhang, Tao; Permentier, Hjalmar; Bischoff, Rainer; Bobrowski, Krzysztof; Chatgilialoglu, Chryssostomos

    2016-01-01

    Important biological consequences are related to the reaction of HO(•) radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest

  7. Gli as a novel therapeutic target in malignant pleural mesothelioma.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available Malignant pleural mesothelioma (MPM is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I. A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.

  8. Sentiment Analysis per analizzare gli effetti del cinema sulla percezione dei luoghi. Il caso pugliese / Sentiment Analysis to study the effects of cinema on the perception of places. The case of Puglia Region

    Directory of Open Access Journals (Sweden)

    Valentina Albanese

    2016-05-01

    Full Text Available Il film induced iourism è un fenomeno ormai indiscutibile e che va affrontato con sistematicità e metodologie sempre più raffinate per consentire ai policy makers di sfruttarne più consapevolmente le potenzialità. In Puglia la realizzazione di pellicole di successo ha provocato effetti turistici e territoriali notevoli. Per poter comprendere realmente se e quanto l’incoming turistico pugliese sia influenzato, nella sua dimensione quantitativa e qualitativa, dall’immagine veicolata dal cinema, si ipotizza qui l’utilizzo di una nuova metodologia di analisi: la Sentiment Analysis. Si intende passare al setaccio i Big Data tematici, tramite una scansione intelligente dei social network e poi riportare le valutazioni (sentiment sul territorio pugliese espresse nei diversi luoghi virtuali di conversazione da parte della domanda turistica. Questa tipologia di studio del dato è del tutto innovativa per il settore cineturistico e può portare ad esiti del tutto inattesi sovvertendo in alcuni casi le interpretazioni prettamente soggettive dei dati quantitativi più tradizionali. Film induced tourism is an undeniable phenomenon and it is necessary to study it sistematically and with sophisticated methods to allow policy makers to exploit, more consciously, its potentiality. In Apulia the successful movies maybe have caused tourism and territorial remarkable effects. In order to understand if and how incoming in Apulia is influenced, in quantitative and qualitative terms, from the image conveyed by cinema, we’ll use a new method of analysis: the Sentiment Analysis. It means making an intelligent scanning of social networks and then bring feedback (sentiment about Apulia expressed in different virtual places of conversation by the tourist demand. This kind of opinion mining study is totally innovative for film induced tourism and can lead to outcomes completely unexpected subverting, in some cases, subjective interpretations of the

  9. The first N-terminal unprotected (Gly-Aib)n peptide: H-Gly-Aib-Gly-Aib-OtBu.

    Science.gov (United States)

    Gessmann, Renate; Brückner, Hans; Petratos, Kyriacos

    2015-12-01

    Glycine (Gly) is incorporated in roughly half of all known peptaibiotic (nonribosomally biosynthesized antibiotic peptides of fungal origin) sequences and is the residue with the greatest conformational flexibility. The conformational space of Aib (α-aminoisobutyric acid) is severely restricted by the second methyl group attached to the Cα atom. Most of the crystal structures containing Aib are N-terminal protected. Deprotection of the N- or C-terminus of peptides may alter the hydrogen-bonding scheme and/or the structure and may facilitate crystallization. The structure reported here for glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid tert-butyl ester, C16H30N4O5, describes the first N-terminal-unprotected (Gly-Aib)n peptide. The achiral peptide could form an intramolecular hydrogen bond between the C=O group of Gly1 and the N-H group of Aib4. This hydrogen bond is found in all tetrapeptides and N-terminal-protected tripeptides containing Aib, apart from one exception. In the present work, this hydrogen bond is not observed (N...O = 5.88 Å). Instead, every molecule is hydrogen bonded to six other symmetry-related molecules with a total of eight hydrogen bonds per molecule. The backbone conformation starts in the right-handed helical region (and the left-handed helical region for the inverted molecule) and reverses the screw sense in the last two residues.

  10. Purim e gli albori del teatro ebraico in Italia

    Directory of Open Access Journals (Sweden)

    Maria Luisa Mayer Modena

    2011-06-01

    Full Text Available The Jewish theatre in Hebrew has its very first beginning in Italy with the "Wedding Comedy" by Leone de Sommi (Mantua, floruit 1550, whose inspiration owes much to the Purim tradition. Jewish theatre, especially the Judaeo-Italian one, continues to flourish until XX century,  always maintaining a strong connection with the Purim celebration. This article will deal with the development of the Jewish theatre - both in Hebrew and in Jewish language -, with  particular emphasis on its relationship with the Purim. In examining the main phases of such  a relevant phenomenon we will rely on the documents currently known, with particular reference  to the Judaeo Italian corpus; one of the first objectives of this work will be to open new perspectives for further research in the field of Jewish dramatic literature.

  11. Glycine transporter GlyT1, but not GlyT2, is expressed in rat dorsal root ganglion--Possible implications for neuropathic pain

    NARCIS (Netherlands)

    Schlösser, Lukas; Barthel, Franziska; Brandenburger, Timo; Neumann, Elena; Bauer, Inge; Eulenburg, Volker; Werdehausen, Robert; Hermanns, Henning

    2015-01-01

    Glycinergic inhibitory neurotransmission plays a pivotal role in the development of neuropathic pain. The glycine concentration in the synaptic cleft is controlled by the glycine transporters GlyT1 and GlyT2. GlyT1 is expressed throughout the central nervous system, while GlyT2 is exclusively

  12. Frigyes Karinthy, Anelli della catena (1929

    Directory of Open Access Journals (Sweden)

    Marinella Lőrinczi

    2017-09-01

    Full Text Available Chains or Chain-links (https://djjr-courses.wdfiles.com/local--files/soc180%3Akarinthy-chain-links/Karinthy-Chain-Links_1929.pdf , a short story of the prolific writer Frigyes Karinthy (Hungary, 1887 - 1938, has an international reputation as it documents the beginnings of the six degree of separation theory. A new Italian translation with notes is presented to the reader.

  13. [CONTATTI SONORI] Morfologia e poetica della musica di Dave Holland fra gli anni Settanta e Ottanta

    Directory of Open Access Journals (Sweden)

    Giuseppe Sergi

    2015-02-01

    Full Text Available La musica del contrabbassista inglese Dave Holland ha radici nel jazz ma dialoga con i linguaggi della tradizione colta. Le esigenze compositive si affiancano alla necessità dell'improvvisazione. Holland espone così la propria poetica: «gli uccelli si riuniscono per cantare insieme, ognuno affermando con il canto la propria libertà. Il mio desiderio è condividere il medesimo spirito con i musicisti e comunicarlo alla gente». Questo studio affronta un'analisi di incisioni significative che mettono in luce i risultati musicali di tale pensiero. Il brano Conference of the birds è un manifesto poetico: esso spicca per le scelte sonore, la metrica, l'incrocio delle voci e le giustapposizioni modali. First snow si caratterizza per la correlazione tra il trattamento armonico e la natura modale delle proposte melodiche. Homecoming presenta una peculiare sequenza di episodi musicali e un significativo rapporto fra soluzioni melodiche e armoniche di carattere tonale e modale. L'analisi solleva interrogativi di rilievo: quali strategie compositive e performative vengono adottate nella musica di Dave Holland? Che legame esse intrattengono con il linguaggio del jazz o della musica 'd'arte'? Che tipo di equilibrio si crea fra la dimensione compositiva e l'improvvisazione? Tentando di fornire risposte a tali domande questo studio mette in luce gli elementi rilevanti della musica di uno maggiori compositori e musicisti del jazz strumentale.

  14. Gli2 activator function in preosteoblasts is sufficient to mediate Ihh-dependent osteoblast differentiation, whereas the repressor function of Gli2 is dispensable for endochondral ossification.

    Science.gov (United States)

    Kesper, Dörthe Andrea; Didt-Koziel, Lydia; Vortkamp, Andrea

    2010-06-01

    Signaling of Indian hedgehog (Ihh), one of the key regulators of endochondral ossification is mediated by transcription factors of the Gli family, Gli1, Gli2, and Gli3. Gli3 and to a lesser extent Gli2 can be proteolytically processed into short repressor proteins. Upon Ihh signaling, processing is inhibited and the full-length proteins function as activators of transcription. Gli3 has been shown to mainly act as a repressor of Ihh target genes in chondrocytes, but the role of other Gli isoforms is less clear. Analyzing mouse mutants deficient for Ihh;Gli2 or Gli3;Gli2, we show here that the Gli2 repressor has no detectable function in chondrocyte or osteoblast differentiation. Instead, Gli2 seems to act as an activator to fully induce the expression of Ihh target genes in skeletal tissues. Furthermore, we show that, in the absence of Gli3, the activator function of Gli2 is sufficient to induce Ihh-dependent osteoblast differentiation.

  15. The position of the Gly-xxx-Gly motif in transmembrane segments modulates dimer affinity.

    Science.gov (United States)

    Johnson, Rachel M; Rath, Arianna; Deber, Charles M

    2006-12-01

    Although the intrinsic low solubility of membrane proteins presents challenges to their high-resolution structure determination, insight into the amino acid sequence features and forces that stabilize their folds has been provided through study of sequence-dependent helix-helix interactions between single transmembrane (TM) helices. While the stability of helix-helix partnerships mediated by the Gly-xxx-Gly (GG4) motif is known to be generally modulated by distal interfacial residues, it has not been established whether the position of this motif, with respect to the ends of a given TM segment, affects dimer affinity. Here we examine the relationship between motif position and affinity in the homodimers of 2 single-spanning membrane protein TM sequences: glycophorin A (GpA) and bacteriophage M13 coat protein (MCP). Using the TOXCAT assay for dimer affinity on a series of GpA and MCP TM segments that have been modified with either 4 Leu residues at each end or with 8 Leu residues at the N-terminal end, we show that in each protein, centrally located GG4 motifs are capable of stronger helix-helix interactions than those proximal to TM helix ends, even when surrounding interfacial residues are maintained. The relative importance of GG4 motifs in stabilizing helix-helix interactions therefore must be considered not only in its specific residue context but also in terms of the location of the interactive surface relative to the N and C termini of alpha-helical TM segments.

  16. Book review. Conoscere gli animali familiari. Francesca Bellini, Alessia Liverini, Vincenzo Rosa

    Directory of Open Access Journals (Sweden)

    Manuel Graziani

    2014-03-01

    Full Text Available Conoscere gli animali familiari è la settima uscita della collana diretta da Paolo Polidori "produzioni animali e sicurezza alimentare" sulla ricerca nell'ambito della nutrizione e alimentazione animale, zootecnia, ispezione degli alimenti di origine animale, clinica medica e parassitologia veterinaria con risvolti di natura tecnica, scientifica e pratica. Il volume, redatto da medici veterinari in servizio presso differenti Aziende Sanitarie italiane, è un sintetico manuale su domesticazione, cura sanitaria, etnografia e addestramento del proprio cane (o gatto. Gli autori partono dall'assunto che i proprietari scelgono il cane per lo più sulla base del gusto visivo o sulla consuetudine tramandata in famiglia, senza un'esaustiva conoscenza degli aspetti riguardanti l'origine dell'animale, la sua attitudine prevalente, le sue patologie ricorrenti e le eventuali predisposizioni genetiche nei confronti di una determinata patologia. Puntano l'accento sin dalle prime battute sul cambiamento culturale che ha modificato anche il rapporto uomo-animale sotto l'aspetto sociale, effettuale e giuridico. L'animale da semplice "res" si è da tempo affermato come un essere diverso ma senziente, quindi destinatario di tutele, con diritti contemplati dalle carte costituzionali di diversi Paesi. Per questo motivo chi detiene un animale domestico deve prepararsi ad un impegno non riducibile al possesso di un oggetto, al punto di risponderne penalmente per eventuali sofferenze fisiche o psicologiche, per l'abbandono (anche solo temporaneo o per l'incuria. Conoscere gli animali familiari fornisce nozioni scientifiche e sanitarie alla portata di tutti, utili soprattutto nelle occasioni in cui i proprietari dovranno recarsi dal veterinario o affrontare visite legate alla profilassi e alle vaccinazioni di routine.

  17. Gli arcipelaghi and Il Figlio di Bakunìn: the narrator in film and novel

    Directory of Open Access Journals (Sweden)

    Myriam Mereu

    2012-12-01

    Full Text Available Obiettivo del presente contributo è analizzare la struttura di due noti romanzi sardi, Il figlio di Bakunìn di Sergio Atzeni e Gli arcipelaghi di Maria Giacobbe, caratterizzati da una narrazione in prima persona, e dimostrare come il materiale narrativo è riorganizzato e riplasmato nelle trasposizioni cinematografiche, dirette rispettivamente da Gianfranco Cabiddu (1997 e da Giovanni Columbu (2001. La locuzione impiegata per riferirsi ai film è quella di traduzione intersemiotica, che riprende la terminologia del linguista Roman Jakobson. In questo modo, si vogliono mettere in evidenza l’intento dei registi di ricreare i fili narrativi dei romanzi e la volontà di riproporre, reintepretandoli, i punti di vista di ciascun personaggio. In un secondo momento, l’attenzione sarà rivolta alle scelte linguistiche adottate nei romanzi e nei film.

  18. Gli studi provenzali nel percorso critico di Cesare De Lollis

    Directory of Open Access Journals (Sweden)

    Diego Stefanelli

    2015-12-01

    Full Text Available L’intervento indaga l’attività di provenzalista di Cesare De Lollis. Sulla scia dell’opera del maestro Ernesto Monaci essa si concentrò inizialmente sull’edizione di codici provenzali e sullo studio dei primordi della provenzalistica nell’umanesimo italiano. Seguì l’edizione dell’opera di Sordello (1896 che innescò un’aspra polemica con Francesco Torraca, da collocarsi nel contesto della querelle tra critica estetica ed erudita. In seguito, la letteratura dei trovatori fu studiata da De Lollis nel suo rapporto con quella italiana. Ripercorrendo i suoi principali interventi di materia provenzale posteriori all’edizione di Sordello, si dimostra come proprio dal confronto tra le due letterature De Lollis individuò una  linea (che dagli ultimi provenzali arrivava fino a Dante, passando per gli stilnovisti e Guittone caratterizzata dal primato della forma. Tale linea fu fondamentale per l’elaborazione di una delle idee forti della critica dello studioso, la dialettica tra tradizione letteraria codificata e margini di libertà espressiva degli autori in essa operanti, che sarà alla base dei Saggi sulla forma poetica italiana dell’Ottocento.The article focuses on Cesare De Lollis’ studies on Occitan Litterature. At first, following Ernesto Monaci’s example, he worked on the editions of Occitan codes and he studied the beginnings of Occitan philology during the Italian Umanesimo. In 1896 he published the critical edition of Sordello, entering into debate with Francesco Torraca: this debate has to be set in the context of the querelle between critica estetica e critica erudita, that was very strong in Italy at the end of XIX century. After the Sordello’s edition, De Lollis studied the relationship between Occitan and Italian Litterature and he identified a poetic tradition (the last troubadours, Guittone, the stilnovisti, Dante, characterized by the importance of the forma. He focused also on the dialectic between a

  19. L’influenza del cinema d’animazione nella promozione (cineturistica delle destinazioni. Gli effetti del fenomeno Frozen sul turismo norvegese / The influence of animation cinema in the (cinetouristic promotion of destinations. The effects of the Frozen phenomenon on Norwegian tourism

    Directory of Open Access Journals (Sweden)

    Enrico Nicosia

    2016-05-01

    Full Text Available Oggi le location sono diventate vere e proprie  destinazioni turistiche,  cioè  luoghi che offrono un insieme di relazioni, prodotti, servizi, elementi naturali ed artificiali, capaci di attrarre un certo numero di visitatori e soddisfarne le attese sia dal punto di vista funzionale che da quello emozionale.  Il Film Induced Tourism è una tendenza che si è affermata negli ultimi anni con la creazione di agenzie turistiche specializzate nel proporre tour guidati alle mete in cui siano state girate famose scene cinematografiche. Secondo diverse statistiche effettuate sul tema del Film Induced Tourism è dimostrato che, anche se è un fenomeno recente, è in crescita nel mercato turistico mondiale e si impone sempre più all’attenzione dei media, dei sociologi e degli operatori turistici. Con questo lavoro si cercherà di analizzare il Film Induced Tourism con l’intento di approcciarsi ad una nuova frontiera: il Cartoon Induced Tourism (il turismo indotto dalla visione di film d’animazione e cartoons, perché non solo la visione di un film o di una serie tv può indurre il potenziale (cineturista a viaggiare. Anche un film d’animazione, che per definizione è pura creazione, può suscitare allo spettatore le stesse emozioni di una pellicola girata in una location “reale” e spingerlo ad esplorare i luoghi da cui i registi hanno preso spunto per costruire o meglio disegnare il set in cui sono ambientati.  Nowadays locations are becoming tourist destinations, offering relations such as products, services, natural and manmade elements, able to attract a certain number of visitors, satisfying expectations from a functional point of view as well as from an emotional one. Film Induced Tourism represent a trend developed in the last years according with the creation of tourist agencies, specialised in guided tour to specific destination in which famous cinematographic scenes have been made. According to various statistics on Film

  20. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

    Directory of Open Access Journals (Sweden)

    Emily F. Winterbottom

    2015-06-01

    Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  1. Gli infortuni lavorativi in minori: risultati di uno studio multicentrico italiano

    Directory of Open Access Journals (Sweden)

    G. Aggazzotti

    2003-05-01

    Full Text Available

    Obiettivi: gli infortuni lavorativi, in particolare quelli subiti da minorenni, rappresentano un problema di notevole importanza sociale: in Italia, da dati INPS, risultano lavorare circa 68 adolescenti su 1000. L’obiettivo di questo studio è stato quello di raccogliere informazioni sugli infortuni lavorativi avvenuti a minori (14-17 anni in 14 città italiane nel periodo gennaio-giugno 2000. Metodi: si tratta di uno studio epidemiologico descrittivo, basato sulle informazioni raccolte consultando direttamente le cartelle cliniche presso centri di Pronto Soccorso (PS attivi nelle città coinvolte. Sono stati presi in considerazione tutti gli infortuni avvenuti a minori: tra questi sono stati considerati come lavorativi quelli accaduti nel corso di attività descritta come lavorativa e quelli occorsi “in itinere”. Le analisi statistiche sono state condotte con SPSS; è stata effettuata una cluster analysis per evidenziare eventuali sottogruppi omogenei. Risultati: la popolazione residente nelle aree indagate di età tra 14 e 17 anni è stata stimata in circa 850.000 soggetti, pari al 31% della popolazione italiana della stessa età: gli infortuni totali sono risultati 13423 di cui 317 lavorativi (2.4%. I soggetti di sesso maschile, diciassettenni, impiegati nel comparto industriale sono risultati il gruppo maggiormente coinvolto: la prognosi è risultata per lo più inferiore a 8 giorni. Sono apparse due diverse tipologie di infortunio: una riguarda i casi avvenuti in itinere, con caratteristiche molto simili agli incidenti stradali, e un’altra, più specifica, riguarda gli eventi sul posto di lavoro, dove si registrano lesioni al polso, alle mani, al capo e agli occhi con frequenza superiore rispetto agli infortuni in genere.

    Conclusioni: il fenomeno è risultato non trascurabile, soprattutto tenendo conto del fatto che si riferisce solamente al lavoro minorile regolarmente

  2. Complementary Gli activity mediates early patterning of the mouse visual system.

    Science.gov (United States)

    Furimsky, Marosh; Wallace, Valerie A

    2006-03-01

    The Sonic hedgehog (Shh) signaling pathway plays a key role in the development of the vertebrate central nervous system, including the eye. This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes. In this study, we investigated the roles of the three vertebrate Glis in mediating midline Shh signaling in early ocular development. We examined the ocular phenotypes of Shh and Gli combination mutant mouse embryos and monitored proximodistal and dorsoventral patterning by the expression of specific eye development regulatory genes using in situ hybridization. We show that midline Shh signaling relieves the repressor activity of Gli3 adjacent to the midline and then promotes eye pattern formation through the nonredundant activities of all three Gli proteins. Gli3, in particular, is required to specify the dorsal optic stalk and to define the boundary between the optic stalk and the optic cup.

  3. Gli Ungulati in Italia: status, gestione e ricerca scientifica

    Directory of Open Access Journals (Sweden)

    Marco Apollonio

    2004-06-01

    managers in public administrations is suggested, as a further step in the development of a proper management of ungulates and other wildlife. Scientific research on ungulates in Italy was, in the last decade, quite uneven both in the species and in the disciplines chosen. There is a clear opportunistic approach to subjects, that often has no link with the real necessities of wildlife management. The development of long term studies is suggested, together with a more efficient coordination among scientist in the choice of the research subjects. Last but not least a more efficient founding mechanisms is needed in order to avoid money waste and to promote serious research programmes. Riassunto Gli Ungulati nel nostro Paese hanno proseguito, nell'ultimo decennio, l'espansione dei loro areali già iniziata nel decennio precedente e, per quanto i dati disponibili possono testimoniare, della loro consistenza. Tale tendenza è particolarmente chiara nel Centro-Nord, mentre nell'area meridionale il processo di sviluppo di popolamenti di ungulati delle diverse specie è rallentato se non assente, sia pure con notevoli eccezioni come la Sardegna dove, grazie ad un'opportuna politica di reintroduzioni, il Cervo sardo (Cervus elaphus corsicanus sta tornando nelle quattro province dell'isola. In questo quadro generale deve essere ricordato il ruolo rilevante dell'aumento degli ungulati nel favorire l'espansione dei grandi predatori, in particolare del Lupo (Canis lupus in ampi settori del paese. La gestione degli ungulati ha anch'essa subito una positiva evoluzione durante l'ultimo decennio sebbene persistano forti differenze fra Centro-Nord e Sud. Reintroduzioni di molte specie, effettuate con procedure nel complesso più corrette di quelle eseguite nel passato, hanno contribuito a colmare le lacune della distribuzione naturale di molte specie. Le statistiche d'abbattimento disponibili hanno dimensioni che suggeriscono un'accresciuta importanza degli

  4. Sinergetica il segreto del successo della natura

    CERN Document Server

    Haken, Hermann

    1983-01-01

    Introduzione e sommario ; il disordine cresce sempre? la morte termica dell'universo ; i cristalli : strutture ordinate, ma morte ; strutture ordinate nei liquidi e nelle nubi e formazioni geologiche ; fiat lux! la luce del laser ; configurazioni chimiche ; l'evoluzione biologica e la sopravvivenza del migliore ; sopravvivi anche senza essere il migliore : specializzati, scavati una nicchia ecologica ; come si formano gli organismi biologici ; talvolta i conflitti sono ineluttabili ; il caos, il caso e la concezione meccanicistica del mondo ; gli effetti sinergetici nell'economia ; si possono prevedere le rivoluzioni ? ; le allucinazioni comprovano le teorie sul cervello.

  5. Il Sistema Gateway nello sviluppo della rete del trasporto combinato in Europa: il caso del terminal di Verona Quadrante Europa

    OpenAIRE

    Grossato, Raffaella

    2008-01-01

    Il trasporto intermodale ha acquisito un ruolo sempre più importante nello scenario dei trasporti comunitari merci durante gli ultimi quindici anni. La sfida che si era posta a inizi anni novanta in Europa consisteva nello sviluppo di una rete europea di trasporto combinato strada-ferrovia. A questo fine è stata fondamentale la cooperazione tra gli operatori del settore e le istituzioni (comunitarie e nazionali), nonché l’impulso dato dalla liberalizzazione del trasporto ferrov...

  6. A Novel Gli3 Enhancer Controls the Gli3 Spatiotemporal Expression Pattern through a TALE Homeodomain Protein Binding Site ▿‡

    OpenAIRE

    Coy, Sarah; Caamaño, Jorge H.; Carvajal, Jaime; Cleary, Michael L.; Borycki, Anne-Gaëlle

    2011-01-01

    The zinc finger transcription factor Gli3 is an essential mediator of hedgehog signaling. Gli3 has a dynamic expression pattern during embryonic development. In the neural tube, Gli3 transcripts are patterned along the anteroposterior and dorsoventral axes such that the initial broad expression in the posterior neural tube becomes dorsally restricted as neurogenesis takes place. Little is known about the molecular mechanisms that regulate this dynamic expression. Here, we report on a phylogen...

  7. Evolution and Functional Diversification of the GLI Family of Transcription Factors in Vertebrates

    Directory of Open Access Journals (Sweden)

    Amir Ali Abbasi

    2009-05-01

    Full Text Available Background: In vertebrates the “SONIC HEDGEHOG” signalling pathway has been implicated in cell-fate determination, proliferation and the patterning of many different cell types and organs. As the GLI family members (GLI1, GLI2 and GLI3 are key mediators of hedgehog morphogenetic signals, over the past couple of decades they have been extensively scrutinized by genetic, molecular and biochemical means. Thus, a great deal of information is currently available about the functional aspects of GLI proteins in various vertebrate species. To address the roles of GLI genes in diversifying the repertoire of the Hh signalling and deploying them for the vertebrate specifications, in this study we have examined the evolutionary patterns of vertebrate GLI sequences within and between species. Results: Phylogenetic tree analysis suggests that the vertebrate GLI1, GLI2 and GLI3 genes diverged after the separation of urochordates from vertebrates and before the tetrapods-bony fishes split. Lineage specific duplication events were also detected. Estimation of mode and strength of selection acting on GLI orthologs demonstrated that all members of the GLI gene family experienced more relaxed selection in teleost fish than in the mammalian lineage. Furthermore, the GLI1 gene appeared to have been exposed to different functional constraints in fish and tetrapod lineages, whilst a similar level of functional constraints on GLI2 and GLI3 was suggested by comparable average non-synonymous (Ka substitutions across the lineages. A relative rate test suggested that the majority of the paralogous copies of the GLI family analyzed evolved with similar evolutionary rates except GLI1 which evolved at a significantly faster rate than its paralogous counterparts in tetrapods. Conclusions: Our analysis shows that sequence evolutionary patterns of GLI family members are largely correlated with the reported similarities and differences in the functionality of GLI proteins

  8. Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

    Directory of Open Access Journals (Sweden)

    Fei He

    Full Text Available Disorders of sexual development (DSD encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E18.5 and adult mice revealed shortened anogenital distance (AGD, open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans.

  9. Gli3 is a negative regulator of Tas1r3-expressing taste cells

    Science.gov (United States)

    Jyotaki, Masafumi; Redding, Kevin; Jiang, Peihua

    2018-01-01

    Mouse taste receptor cells survive from 3–24 days, necessitating their regeneration throughout adulthood. In anterior tongue, sonic hedgehog (SHH), released by a subpopulation of basal taste cells, regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration. Using single-cell RNA-Seq we found that Gli3 is highly expressed in Tas1r3-expressing taste receptor cells and Lgr5+ taste stem cells in posterior tongue. By PCR and immunohistochemistry we found that Gli3 was expressed in taste buds in all taste fields. Conditional knockout mice lacking Gli3 in the posterior tongue (Gli3CKO) had larger taste buds containing more taste cells than did control wild-type (Gli3WT) mice. In comparison to wild-type mice, Gli3CKO mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3CKO taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3CKO mice and/or organoids. Mirroring these changes, Gli3CKO mice had increased lick responses to sweet and umami stimuli, decreased lick responses to bitter and sour taste stimuli, and increased glossopharyngeal taste nerve responses to sweet and bitter compounds. Our results indicate that Gli3 is a suppressor of stem cell proliferation that affects the number and function of mature taste cells, especially Tas1r3+ cells, in adult posterior tongue. Our findings shed light on the role of the Shh pathway in adult taste cell regeneration and may help devise strategies for treating taste distortions from chemotherapy and aging. PMID:29415007

  10. Inflammation and Gli2 suppress gastrin gene expression in a murine model of antral hyperplasia.

    Directory of Open Access Journals (Sweden)

    Milena Saqui-Salces

    Full Text Available Chronic inflammation in the stomach can lead to gastric cancer. We previously reported that gastrin-deficient (Gast⁻/⁻ mice develop bacterial overgrowth, inflammatory infiltrate, increased Il-1β expression, antral hyperplasia and eventually antral tumors. Since Hedgehog (Hh signaling is active in gastric cancers but its role in precursor lesions is poorly understood, we examined the role of inflammation and Hh signaling in antral hyperplasia. LacZ reporter mice for Sonic hedgehog (Shh, Gli1, and Gli2 expression bred onto the Gast⁻/⁻ background revealed reduced Shh and Gli1 expression in the antra compared to wild type controls (WT. Gli2 expression in the Gast⁻/⁻ corpus was unchanged. However in the hyperplastic Gast⁻/⁻ antra, Gli2 expression increased in both the mesenchyme and epithelium, whereas expression in WT mice remained exclusively mesenchymal. These observations suggested that Gli2 is differentially regulated in the hyperplastic Gast⁻/⁻ antrum versus the corpus and by a Shh ligand-independent mechanism. Moreover, the proinflammatory cytokines Il-1β and Il-11, which promote gastric epithelial proliferation, were increased in the Gast⁻/⁻ stomach along with Infγ. To test if inflammation could account for elevated epithelial Gli2 expression in the Gast⁻/⁻ antra, the human gastric cell line AGS was treated with IL-1β and was found to increase GLI2 but decrease GLI1 levels. IL-1β also repressed human GAST gene expression. Indeed, GLI2 but not GLI1 or GLI3 expression repressed gastrin luciferase reporter activity by ∼50 percent. Moreover, chromatin immunoprecipitation of GLI2 in AGS cells confirmed that GLI2 directly binds to the GAST promoter. Using a mouse model of constitutively active epithelial GLI2 expression, we found that activated GLI2 repressed Gast expression but induced Il-1β gene expression and proliferation in the gastric antrum, along with a reduction of the number of G-cells. In summary

  11. Attraverso gli studi spagnoli di Cesare de Lollis (1887-1924

    Directory of Open Access Journals (Sweden)

    Diego Stefanelli

    2016-07-01

    Full Text Available L’articolo considera gli studi di ispanistica di Cesare De Lollis nel loro complesso: dalla fine dell’Ottocento, con gli articoli sulla lirica ispano-portoghese medievale (di stampo filologico-erudito e gli interventi (di tipo giornalistico-divulgativo su alcuni scrittori spagnoli dell’Ottocento, agli anni Venti del Novecento, con il volume su Cervantes reazionario (1924. Un momento importante di questo percorso fu il passaggio di De Lollis alla cattedra romana di «Letterature francese e spagnola moderne» (avvenuto nel 1905: ricostruite le vicende della cattedra, si pone l’attenzione sugli scritti coevi di De Lollis incentrati sulla necessità di uno studio serio delle letterature moderne. Vengono poi studiate le note e le recensioni di letteratura spagnola apparse nelle prime decadi del secolo, in particolare lo scritto Classicismo e secentismo (1908 su Fernando de Herrera, esponente di quella poesia «eroica» studiata a piú riprese da De Lollis (in particolare per il contesto francese. L’articolo si concentra poi sul volume Cervantes reazionario, mostrando che molte delle questioni trattate erano presenti già nel primo articolo del 1913, contemporaneo a quelli sui romantici italiani confluiti poi nei Saggi sulla forma poetica italiana dell’Ottocento. Proprio il nesso tra questi scritti e quelli su Cervantes consente di leggere il volume cervantino alla luce di un tema centrale della critica di De Lollis: la contrapposizione tra l’«eroe» della poesia classicistica e il «realismo» della rivoluzione romantica.  The paper deals with Cesare De Lollis’ Hispanic Studies from the end of the 19th Century (with the philological studies on Spanish-Portuguese poetry of the Middle Age and the coeval journalistic articles on Spanish writers of the 19th Century to the book Cervantes reazionario (1924. A turning moment in De Lollis’ approach to Spanish literature is 1905, when he obtained the chair of «Modern French and Spanish

  12. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  13. Peptide analysis as amino alcohols by gas chromatography-mass spectrometry. Application to hyperoligopeptiduria. Detection of Gly-3Hyp-4Hyp and Gly-Pro-4Hyp-Gly.

    Science.gov (United States)

    Steiner, W; Niederwieser, A

    1979-03-15

    A method for the qualitative analysis of oligopeptides in human urine in cases of peptiduria is described. After sample precleaning on a strongly acidic ion exchanger, the trifluoroacetyl/methyl esters were formed and the peptide derivatives were transformed into trifluoroethyl oligoamino alcohols according to Nau and Biemann. It was found that oligoamino alcohols could be isolated selectively on a weakly acidic ion exchanger. The O-trimethylsilylated trifluoroethyl oligoamino alcohols were separated on a SE-30 glass capillary column and analyzed by computer-assisted gas chromatography-mass spectrometry. In order to increase specificity and to facilitate mass spectrometric interpretation, aliquots of the sample were reduced separately with lithium-aluminium deuteride and hydride. Each peptide gave a pair of derivatives with characteristic mass differences of the ions, namely 2 mass units per reduced oxo group (deuterium-hydrogen-labelling of oxo groups by reduction). Correct identification is assumed only if both mass spectral patterns fit the theory. Sample volumes of 5--100 ml of urine are needed. About six samples can be derivatized per week. Three cases with suspected peptiduria were investigated and the following peptides were found: Gly-Pro-4Hyp-Gly; Gly-Pro-4Hyp; Gly-Hyp-Hyp (postulated isomer Gly-3Hyp-4Hyp); Pro-4Hyp and Gly-Pro. With exception of the tetrapeptide, these compounds could be detected also in the urine of a healthy child.

  14. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

    2016-06-01

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

  15. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Erlach, Markus Beck; Koehler, Joerg [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Crusca, Edson [University of São Paulo, Physics Institute of São Carlos (Brazil); Kremer, Werner [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Munte, Claudia E. [University of São Paulo, Physics Institute of São Carlos (Brazil); Kalbitzer, Hans Robert, E-mail: hans-robert.kalbitzer@biologie.uni-regensburg.de [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany)

    2016-06-15

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms {sup 1}H{sup α}, {sup 13}C{sup α} and {sup 13}C′ in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2} (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B{sub 1} and B{sub 2} are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.Graphical Abstract.

  16. Application of evolutionary algorithm methods to polypeptide folding: comparison with experimental results for unsolvated Ac-(Ala-Gly-Gly)5-LysH+

    DEFF Research Database (Denmark)

    Damsbo, Martin; Kinnear, Brian S; Hartings, Matthew R

    2004-01-01

    We present an evolutionary method for finding the low-energy conformations of polypeptides. The application, called FOLDAWAY,is based on a generic framework and uses several evolutionary operators as well as local optimization to navigate the complex energy landscape of polypeptides. It maintains...... mobility measurements. It has a flat energy landscape where helical and globular conformations have similar energies. FOLDAWAY locates several large groups of structures not found in previous molecular dynamics simulations for this peptide, including compact globular conformations, which are probably...... two complementary representations of the structures and uses the CHARMM force field for evaluating the energies. The method is applied to unsolvated Met-enkephalin and Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+). Unsolvated Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+) has been the object of recent experimental studies using ion...

  17. “Economic heritage impact assessment” come strumento per valutare gli impatti dei grandi progetti di riqualificazione delle città costiere siti Unesco. Il caso studio di Torre Annunziata nel golfo di Napoli

    Directory of Open Access Journals (Sweden)

    Mariarosaria Angrisano

    2015-12-01

    Full Text Available Quest’articolo parte dallo studio delle città portuali storiche, siti UNESCO, che oggi affrontano la sfida della riqualificazione dei waterfront urbani attraverso la conservazione del patrimonio culturale e paesaggistico. Le raccomandazioni sull’ “Historic Urban Landscape”, e gli strumenti operativi promossi dall’ICOMOS “Guidance on Heritage Impact Assessments for Cultural World Heritage Properties” del 2011, si configurano come le più recenti disposizioni concernenti la conservazione, protezione e valorizzazione del patrimonio culturale (Fusco Girard, 2010. La Guida ICOMOS è stata considerata lo strumento più adatto per valutare gli impatti dei grandi progetti di riqualificazione dei waterfront urbani sul patrimonio culturale. Per comprendere al meglio tale strumento è stata fatta un’applicazione per valutare gli impatti del Grande Progetto Pompei sul waterfront di Torre Annunziata, città costiera nel Golfo di Napoli sito UNESCO. A questa fase di analisi segue una riflessione su come migliorare l’Heritage Impact Assessment, come strumento capace di valutare non soltanto gli impatti culturali ma anche quelli economici, per parlare di “economia del patrimonio culturale”. La proposta ultima è quella di affiancare al processo di “Heritage Impact Assessment” una valutazione degli impatti economici, attraverso un’analisi costi-benefici, per quantificare in termini monetari la convenienza degli investimenti nella conservazione del patrimonio storico urbano delle città costiere, proponendo una “Economic Heritage Impact Assessment” (EHIA. Tale metodo, elaborato dall’autrice all’interno della tesi di dottorato “Il paesaggio storico urbano delle città costiere: sfide e opportunità. Il caso Torre Annunziata”, offre la possibilità di superare la sola valutazione degli impatti culturali proposta dall’ICOMOS.

  18. La misurazione dei processi di regolazione cognitiva e metacognitiva durante lo studio con gli ipermedia

    Directory of Open Access Journals (Sweden)

    Roger Azevedo

    2010-01-01

    Full Text Available L’apprendimento autoregolato rappresenta una modalità di apprendimento di fondamentale importanza quando ci si avvale del supporto di ambienti ipermediali. Obiettivo di questo articolo è presentare quattro assunzioni chiave che consentono la misurazione dei processi cognitivi e metacognitivi attivati durante l’apprendimento tramite ipermedia. Innanzi tutto, assumiamo che sia possibile individuare, tracciare, modellare e favorire processi di apprendimento auto-regolato durante lo studio con gli ipermedia. La seconda assunzione si focalizza sul comprendere come la complessità dei processi regolatori che avvengono durante l’apprendimento mediato da sistemi ipermediali sia importante per determinare il perché alcuni processi vengono messi in atto durante l’esecuzione di un compito. Le terza assunzione è relativa al considerare che l’utilizzo di processi di apprendimento auto-regolato possa dinamicamente cambiare nel tempo e che tali processi sono di natura ciclica (influenzati dalle condizioni interne ed esterne e da meccanismi di feedback. Infine, l’identificazione, raccolta e classificazione dei processi di apprendimento autoregolato utilizzati durante lo studio con sistemi ipermediali, può risultare un compito alquanto difficoltoso.

  19. Effects of Pro-Gly-Pro tripeptide on the dopamine system.

    Science.gov (United States)

    Meshavkin, V K; Batishcheva, E Yu; Kost, N V; Sokolov, O Yu; Trufanova, A V; Samonina, G E

    2011-08-01

    Tripeptide Pro-Gly-Pro interacted with dopamine receptors in vitro and reduced behavioral manifestations of apomorphine-induced hyperfunction of the dopamine system in verticalization, stereotypy, and yawning tests. Presumably, the behavioral effects of Pro-Gly-Pro tripeptide were mediated through post- and presynaptic D(2)and D(3)receptors.

  20. I misteri del tempo l'universo dopo Einstein

    CERN Document Server

    Davies, Paul

    1996-01-01

    Quando fu esattamente l'inizio del tempo? Il viaggio nel tempo è realtà o fantasia? Sono possibili gli esperimenti con il tempo? Questo importante saggio indaga sull'enigma del tempo, un tema affascinante da sempre al centro delle speculazioni scientifiche e religiose.

  1. Pressure dependence of side chain 13C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Beck Erlach, Markus; Koehler, Joerg; Crusca, Edson; Munte, Claudia E; Kainosho, Masatsune; Kremer, Werner; Kalbitzer, Hans Robert

    2017-10-01

    For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of 13 C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH 2 (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B 1 and B 2 is dependent on the type of atom and amino acid studied. For H N , N and C α the first order pressure coefficient B 1 is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically 13 C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.

  2. Gli3 Regulation of Myogenesis Is Necessary for Ischemia-Induced Angiogenesis

    Science.gov (United States)

    Renault, Marie-Ange; Vandierdonck, Soizic; Chapouly, Candice; Yu, Yang; Qin, Gangjian; Metras, Alexandre; Couffinhal, Thierry; Losordo, Douglas W.; Yao, Qinyu; Reynaud, Annabel; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Desgranges, Claude; Gadeau, Alain-Pierre

    2015-01-01

    Rationale A better understanding of the mechanism underlying skeletal muscle repair is required to develop therapies that promote tissue regeneration in adults. Hedgehog signaling has been shown previously to be involved in myogenesis and angiogenesis: 2 crucial processes for muscle development and regeneration. Objective The objective of this study was to identify the role of the hedgehog transcription factor Gli3 in the crosstalk between angiogenesis and myogenesis in adults. Methods and Results Using conditional knockout mice, we found that Gli3 deficiency in endothelial cells did not affect ischemic muscle repair, whereas in myocytes, Gli3 deficiency resulted in severely delayed ischemia-induced myogenesis. Moreover, angiogenesis was also significantly impaired in HSA-CreERT2; Gli3Flox/Flox mice, demonstrating that impaired myogenesis indirectly affects ischemia-induced angiogenesis. The role of Gli3 in myocytes was then further investigated. We found that Gli3 promotes myoblast differentiation through myogenic factor 5 regulation. In addition, we found that Gli3 regulates several proangiogenic factors, including thymidine phosphorylase and angiopoietin-1 both in vitro and in vivo, which indirectly promote endothelial cell proliferation and arteriole formation. In addition, we found that Gli3 is upregulated in proliferating myoblasts by the cell cycle–associated transcription factor E2F1. Conclusions This study shows for the first time that Gli3-regulated postnatal myogenesis is necessary for muscle repair–associated angiogenesis. Most importantly, it implies that myogenesis drives angiogenesis in the setting of skeletal muscle repair and identifies Gli3 as a potential target for regenerative medicine. PMID:24044950

  3. Identification of RegIV as a novel GLI1 target gene in human pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2011-04-01

    Full Text Available GLI1 is the key transcriptional factor in the Hedgehog signaling pathway in pancreatic cancer. RegIV is associated with regeneration, and cell growth, survival, adhesion and resistance to apoptosis. We aimed to study RegIV expression in pancreatic cancer and its relationship to GLI1.GLI1 and RegIV expression were evaluated in tumor tissue and adjacent normal tissues of pancreatic cancer patients and 5 pancreatic cancer cell lines by qRT-PCR, Western blot, and immunohistochemistry (IHC, and the correlation between them. The GLI1-shRNA lentiviral vector was constructed and transfected into PANC-1, and lentiviral vector containing the GLI1 expression sequence was constructed and transfected into BxPC-3. GLI1 and RegIV expression were evaluated by qRT-PCR and Western blot. Finally we demonstrated RegIV to be the target of GLI1 by chromatin immunoprecipitation (CHIP and electrophoretic mobility shift assays (EMSA.The results of IHC and qRT-PCR showed that RegIV and GLI1 expression was higher in pancreatic cancer tissues versus adjacent normal tissues (p<0.001. RegIV expression correlated with GLI1 expression in these tissues (R = 0.795, p<0.0001. These results were verified for protein (R = 0.939, p = 0.018 and mRNA expression (R = 0.959, p = 0.011 in 5 pancreatic cancer cell lines. RegIV mRNA and protein expression was decreased (94.7±0.3%, 84.1±0.5%; respectively when GLI1 was knocked down (82.1±3.2%, 76.7±2.2%; respectively by the RNAi technique. GLI1 overexpression in mRNA and protein level (924.5±5.3%, 362.1±3.5%; respectively induced RegIV overexpression (729.1±4.3%, 339.0±3.7%; respectively. Moreover, CHIP and EMSA assays showed GLI1 protein bound to RegIV promotor regions (GATCATCCA in pancreatic cancer cells.GLI1 promotes RegIV transcription by binding to the RegIV gene promoter in pancreatic cancer.

  4. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    OpenAIRE

    Tukachinsky, Hanna; Lopez, Lyle V.; Salic, Adrian

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in wh...

  5. The new industrial political tools based on the sustainable development of productive activities; Gli strumenti attuativi di una politica di sviluppo sostenibile dell'impresa

    Energy Technology Data Exchange (ETDEWEB)

    Luciani, R.; Andriola, L. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1999-07-01

    The new industrial political tools based on the sustainable development of productive activities, and originating at the Rio Conference in 1992, late introduced by the European Union, the Government and voluntary organizations (ISO, CEM, UNI) are gradually entering the market, thereby underling their effect in terms of industrial competitiveness. The main tools were examined in the report and mostly refer to the voluntary ones which, in surpassing the command and control logic, increasingly tend to get close to traditional fiscal, tariff and financial ones. Voluntary agreements, environmental management systems (EMAS, ISO14000), the risk prevention systems (UNI 10617), certification (Ecolabel, ISO 14040) and environment communications tools (environment balance sheet, environmental report, environmental statement) are synthetically described. Finally, the tools regarding the incentives still under Government concern an their diffusion are examined. [Italian] I nuovi strumenti di politica industriale orientati allo sviluppo sostenibile delle attivita' produttive che traggono origine dalla Conferenza di Rio del 1992 e sono stati introdotti successivamente da parte della Comunita' Europea, dal Governo e dagli organismi di normazione volontaria (ISO, CEN, UNI), stanno gradualmente penetrando sul mercato facendo valere i loro effetti anche in termini di competitivita' delle imprese. Nel rapporto sono stati esaminati i principali tra questi strumenti con particolare riferimento a quelli volontari che sempre piu', nel superamento della logica del {sup c}ommand-control{sup ,} tendono ad affiancarsi a quelli tradizionali di carattere fiscale, tariffario e finanziario. In particolare vengono descritti sinteticamente gli accordi volontari, i sistemi di gestione ambientali e della sicurezza (EMAS, norme ISO 14001 e UNI 10617), la certificazione di prodotto (Ecolabel, norma ISO 14040) e gli strumenti di comunicazione ambientale (bilancio ambientale, rapporto

  6. The new industrial political tools based on the sustainable development of productive activities; Gli strumenti attuativi di una politica di sviluppo sostenibile dell'impresa

    Energy Technology Data Exchange (ETDEWEB)

    Luciani, R; Andriola, L [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1999-07-01

    The new industrial political tools based on the sustainable development of productive activities, and originating at the Rio Conference in 1992, late introduced by the European Union, the Government and voluntary organizations (ISO, CEM, UNI) are gradually entering the market, thereby underling their effect in terms of industrial competitiveness. The main tools were examined in the report and mostly refer to the voluntary ones which, in surpassing the command and control logic, increasingly tend to get close to traditional fiscal, tariff and financial ones. Voluntary agreements, environmental management systems (EMAS, ISO14000), the risk prevention systems (UNI 10617), certification (Ecolabel, ISO 14040) and environment communications tools (environment balance sheet, environmental report, environmental statement) are synthetically described. Finally, the tools regarding the incentives still under Government concern an their diffusion are examined. [Italian] I nuovi strumenti di politica industriale orientati allo sviluppo sostenibile delle attivita' produttive che traggono origine dalla Conferenza di Rio del 1992 e sono stati introdotti successivamente da parte della Comunita' Europea, dal Governo e dagli organismi di normazione volontaria (ISO, CEN, UNI), stanno gradualmente penetrando sul mercato facendo valere i loro effetti anche in termini di competitivita' delle imprese. Nel rapporto sono stati esaminati i principali tra questi strumenti con particolare riferimento a quelli volontari che sempre piu', nel superamento della logica del {sup c}ommand-control{sup ,} tendono ad affiancarsi a quelli tradizionali di carattere fiscale, tariffario e finanziario. In particolare vengono descritti sinteticamente gli accordi volontari, i sistemi di gestione ambientali e della sicurezza (EMAS, norme ISO 14001 e UNI 10617), la certificazione di prodotto (Ecolabel, norma ISO 14040) e gli strumenti di comunicazione ambientale (bilancio ambientale, rapporto ambientale

  7. Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6

    Directory of Open Access Journals (Sweden)

    Price David J

    2006-10-01

    Full Text Available Abstract Background Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3+/- mice. Results We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6+/- mutants or than would be predicted by addition of their phenotypes. Conclusion These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.

  8. Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function.

    Science.gov (United States)

    Shimoyama, Atsuko; Wada, Masahiro; Ikeda, Fumiyo; Hata, Kenji; Matsubara, Takuma; Nifuji, Akira; Noda, Masaki; Amano, Katsuhiko; Yamaguchi, Akira; Nishimura, Riko; Yoneda, Toshiyuki

    2007-07-01

    Genetic and cell biological studies have indicated that Indian hedgehog (Ihh) plays an important role in bone development and osteoblast differentiation. However, the molecular mechanism by which Ihh regulates osteoblast differentiation is complex and remains to be fully elucidated. In this study, we investigated the role of Ihh signaling in osteoblast differentiation using mesenchymal cells and primary osteoblasts. We observed that Ihh stimulated alkaline phosphatase (ALP) activity, osteocalcin expression, and calcification. Overexpression of Gli2- but not Gli3-induced ALP, osteocalcin expression, and calcification of these cells. In contrast, dominant-negative Gli2 markedly inhibited Ihh-dependent osteoblast differentiation. Ihh treatment or Gli2 overexpression also up-regulated the expression of Runx2, an essential transcription factor for osteoblastogenesis, and enhanced the transcriptional activity and osteogenic action of Runx2. Coimmunoprecipitation analysis demonstrated a physical interaction between Gli2 and Runx2. Moreover, Ihh or Gli2 overexpression failed to increase ALP activity in Runx2-deficient mesenchymal cells. Collectively, these results suggest that Ihh regulates osteoblast differentiation of mesenchymal cells through up-regulation of the expression and function of Runx2 by Gli2.

  9. New insights into genotype-phenotype correlation for GLI3 mutations.

    Science.gov (United States)

    Démurger, Florence; Ichkou, Amale; Mougou-Zerelli, Soumaya; Le Merrer, Martine; Goudefroye, Géraldine; Delezoide, Anne-Lise; Quélin, Chloé; Manouvrier, Sylvie; Baujat, Geneviève; Fradin, Mélanie; Pasquier, Laurent; Megarbané, André; Faivre, Laurence; Baumann, Clarisse; Nampoothiri, Sheela; Roume, Joëlle; Isidor, Bertrand; Lacombe, Didier; Delrue, Marie-Ange; Mercier, Sandra; Philip, Nicole; Schaefer, Elise; Holder, Muriel; Krause, Amanda; Laffargue, Fanny; Sinico, Martine; Amram, Daniel; André, Gwenaelle; Liquier, Alain; Rossi, Massimiliano; Amiel, Jeanne; Giuliano, Fabienne; Boute, Odile; Dieux-Coeslier, Anne; Jacquemont, Marie-Line; Afenjar, Alexandra; Van Maldergem, Lionel; Lackmy-Port-Lis, Marylin; Vincent-Delorme, Catherine; Chauvet, Marie-Liesse; Cormier-Daire, Valérie; Devisme, Louise; Geneviève, David; Munnich, Arnold; Viot, Géraldine; Raoul, Odile; Romana, Serge; Gonzales, Marie; Encha-Razavi, Ferechte; Odent, Sylvie; Vekemans, Michel; Attie-Bitach, Tania

    2015-01-01

    The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype-phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype-phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.

  10. New insights into genotype–phenotype correlation for GLI3 mutations

    Science.gov (United States)

    Démurger, Florence; Ichkou, Amale; Mougou-Zerelli, Soumaya; Le Merrer, Martine; Goudefroye, Géraldine; Delezoide, Anne-Lise; Quélin, Chloé; Manouvrier, Sylvie; Baujat, Geneviève; Fradin, Mélanie; Pasquier, Laurent; Megarbané, André; Faivre, Laurence; Baumann, Clarisse; Nampoothiri, Sheela; Roume, Joëlle; Isidor, Bertrand; Lacombe, Didier; Delrue, Marie-Ange; Mercier, Sandra; Philip, Nicole; Schaefer, Elise; Holder, Muriel; Krause, Amanda; Laffargue, Fanny; Sinico, Martine; Amram, Daniel; André, Gwenaelle; Liquier, Alain; Rossi, Massimiliano; Amiel, Jeanne; Giuliano, Fabienne; Boute, Odile; Dieux-Coeslier, Anne; Jacquemont, Marie-Line; Afenjar, Alexandra; Van Maldergem, Lionel; Lackmy-Port-Lis, Marylin; Vincent- Delorme, Catherine; Chauvet, Marie-Liesse; Cormier-Daire, Valérie; Devisme, Louise; Geneviève, David; Munnich, Arnold; Viot, Géraldine; Raoul, Odile; Romana, Serge; Gonzales, Marie; Encha-Razavi, Ferechte; Odent, Sylvie; Vekemans, Michel; Attie-Bitach, Tania

    2015-01-01

    The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype–phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype–phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues. PMID:24736735

  11. Brasile 1960: Gli anni della svolta per Alberto Moravia

    Directory of Open Access Journals (Sweden)

    Simone Casini

    2016-06-01

    Full Text Available Alberto Moravia arrived in Brazil in the summer of 1960 to preside the Congress of the PEN Club. He had recently finished La noia, his eleventh novel, the one that most directly is connected to his first novel, Gli indifferenti (1929, and it marks a decisive turning point in his artistic, intellectual, and human course. The essay reconstructs the life and work of the 50-year-old writer, in which a 10-year research is summarized and concluded, opening a new phase. Rereading the articles written for Il Corriere della Sera and the review of the Quarto de despejo by Carolina de Jesus, we focused on the origin and acute reflection of Moravia about Brazil in those years (Brasilia, Bahia, Rio, between past and future. The experience of Brazil, for the writer, who in those following years will attempt new paths in the intellectual and literary field, and new goals for his travels, always more oriented, in the company of Dacia Maraini and Pier Paolo Pasolini, toward the Third World.

  12. GIANFRANCO BETTETINI, Il timpano dell’occhio. Gli intrecci e i giochi dei suoni e delle immagini, Milano, Bompiani, 2009

    Directory of Open Access Journals (Sweden)

    Alessandro Bratus

    2013-12-01

    Full Text Available Il timpano dell’occhio di Gianfranco Bettetini è uno studio dedicato all’analisi semiotica dei testi audiovisivi. Nel volume l’autore si propone di indagare gli effetti che l’azione «strutturalmente sinergica e compatta» (p. 9 di suono e immagine produce sullo spettatore. Lungo tale percorso, Bettetini affronta un nodo cruciale degli studi attuali sulla comunicazione audiovisiva, offrendo allo stesso tempo un prezioso compendio della letteratura semiotica sull’argomento. Nella prima parte del volume lo studioso definisce le linee essenziali di un nuovo approccio metodologico che integra, con la sociologia e la psicologia, il quadro delle discipline che si sono occupate sistematicamente di analisi del testo filmico dal secondo dopoguerra in avanti. Nella seconda parte l’autore prende in esame quattro lungometraggi: Caterina va in città (2003 di Paolo Virzì, Notturno Bus (2007 di Davide Marengo, Il flauto magico (2007 di Kenneth Branagh e La fine del mondo – Ministoria della musica in un tempo (1969 dello stesso Bettetini.

  13. Signal interaction of Hedgehog/GLI and epidermal growth factor receptor signaling in cancer development

    International Nuclear Information System (INIS)

    Eberl, M.

    2012-01-01

    The subject of this PhD thesis is based on the cooperation of Hedgehog (HH)/GLI with epidermal growth factor receptor (EGFR) signaling synergistically promoting oncogenic transformation and cancer growth. In previous studies we have demonstrated that the HH/GLI and EGFR signaling pathways interact synergistically resulting not only in selective induction of HH/GLI-EGFR target genes, but also in the onset of oncogenic transformation and tumor formation (Kasper, Schnidar et al. 2006; Schnidar, Eberl et al. 2009). However, the molecular key mediators acting downstream of HH/GLI and EGFR signal cooperation were largely unknown and the in vivo evidence for the therapeutic relevance of HH/GLI and EGFR signal cooperation in HH-associated cancers was lacking. During my PhD thesis I could demonstrate that the integration of EGFR and HH/GLI signaling involves activation of RAS/MEK/ERK and JUN/AP1 signaling in response to EGFR activation. Furthermore I succeeded in identifying genes, including stem cell- (SOX2, SOX9), tumor growth- (JUN, TGFA, FGF19) and metastasis-associated genes (SPP1/osteopontin, CXCR4) that showed synergistic transcriptional activation by HH/GLI-EGFR signal integration. Importantly, I could demonstrate that these genes arrange themselves within a stable interdependent signaling network, which is required for in vivo growth of basal cell carcinoma (BCC) and tumor-initiating pancreatic cancer cells. These data validate EGFR signaling as additional drug target in HH/GLI driven cancers and provide new therapeutic strategies based on combined targeting of cooperative HH/GLI-EGFR signaling and selected downstream target genes (Eberl, Klingler et al. 2012). (author) [de

  14. Meanings of a Territorial Infrastructure: the Airports Significati di una infrastruttura territoriale: gli aeroporti

    Directory of Open Access Journals (Sweden)

    Giuseppe Mazzeo

    2011-11-01

    lacking of physical and spatial integration with their urban context; for this the airports have evolved into semi-autonomous spaces. For their dimensional characteristics and for the incidence of pollutants factors, must be placed outside the city, often at significant distances from the same: their fundamental role in the urban structure is expressed, therefore, in external spaces from the city. As defined above, the airport is an urban infrastructure. But it is other things also: it is an ordered place, because its management requires defined actions and sequences of activities that are the true opposite of the urban disorder. Both the structures are complexes but the airport is a side where the hierarchical roles are well defined, more than in other sides, and it is the side where the authority is recognized and well accepted. The building of new airports, or the modernization of existing structures are a sign of the sectors’ vitality and of the necessity to offer better services to an expanding custom. But the airports have created a lot of imagines around their presence and use.

    mplessi, ma il primo è uno spazio in cui i ruoli gerarchici sono ben definiti e dove è l'autorità è riconosciuta e ben accettata.

     

    La costruzione di nuovi aeroporti, o l'ammodernamento delle strutture esistenti, è un segno della vitalità del settore e della necessità di offrire migliori servizi ad una utenza in espansione.

    L’articolo vuole esplorare i significati principali di una infrastruttura come l’aeroporto. Essa è una infrastruttura territoriale che aumenta l'accessibilità spaziale e il potenziale economico di un territorio; in questo senso, è una porta per incrementare gli scambi turistici e culturali. È anche una infrastruttura che porta con sé gli investimenti in altre aree della mobilità. A partire dagli anni Sessanta, inoltre, è diventato una icona e un luogo simbolico dove sperimentare nuove soluzioni architettoniche. Sono fattori limitativi

  15. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization.

    Science.gov (United States)

    Joeng, Kyu Sang; Long, Fanxin

    2009-12-01

    Indian hedgehog (Ihh) critically regulates multiple aspects of endochondral bone development. Although it is generally believed that all Ihh functions are mediated by the Gli family of transcription activators and repressors, formal genetic proof for this notion has not been provided. Moreover, the extent to which different Gli proteins contribute to Ihh functions is not fully understood. Previous work has shown that de-repression of the Gli3 repressor is the predominant mode through which Ihh controls chondrocyte proliferation and maturation, but that osteoblast differentiation and hypertrophic cartilage vascularization require additional mechanisms. To test the involvement of Gli2 activation in these processes, we have generated a mouse strain that expresses a constitutive Gli2 activator in a Cre-dependent manner, and have attempted to rescue the Ihh-null mouse with the Gli2 activator, either alone or in combination with Gli3 removal. Here, we report that the Gli2 activator alone is sufficient to induce vascularization of the hypertrophic cartilage in the absence of Ihh but requires simultaneous removal of Gli3 to restore osteoblast differentiation. These results therefore provide direct genetic evidence that Gli2 and Gli3 collectively mediate all major aspects of Ihh function during endochondral skeletal development.

  16. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation

    DEFF Research Database (Denmark)

    Malatesta, Martina; Steinhauer, Cornelia; Mohammad, Faizaan

    2013-01-01

    The Hedgehog (Hh) signaling pathway plays an important role in embryonic patterning and development of many tissues and organs as well as in maintaining and repairing mature tissues in adults. Uncontrolled activation of the Hh-Gli pathway has been implicated in developmental abnormalities as well...... that the histone acetyltransferase PCAF/KAT2B is an important factor of the Hh pathway. Specifically, we show that PCAF depletion impairs Hh activity and reduces expression of Hh target genes. Consequently, PCAF downregulation in medulloblastoma and glioblastoma cells leads to decreased proliferation and increased...... apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells...

  17. Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2.

    Science.gov (United States)

    Mostyn, Shannon N; Carland, Jane E; Shimmon, Susan; Ryan, Renae M; Rawling, Tristan; Vandenberg, Robert J

    2017-09-20

    It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC 50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 μM. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors.

  18. Gruppi, anelli di Lie e teoria della coomologia

    CERN Document Server

    Zappa, G

    2011-01-01

    This book includes: R. Baer: Complementation in finite gropus; M. Lazard: Groupes, anneaux de Lie et probleme de Burnside; J. Tits: Sur les groupes algebriques afffines; Theoremes fondamentaux de structure; and, Classification des groupes semisimples et geometries associees.

  19. Identification of a 3rd Na+ Binding Site of the Glycine Transporter, GlyT2.

    Directory of Open Access Journals (Sweden)

    Nandhitha Subramanian

    Full Text Available The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown. A bacterial betaine transporter, BetP, has also been crystallized and shows structural similarity to LeuTAa. Although betaine transport by BetP is coupled to the co-transport of two Na+ ions, the first Na+ site is not conserved between BetP and LeuTAa, the so called Na1' site. We hypothesized that the third Na+ binding site (Na3 site of GlyT2 corresponds to the BetP Na1' binding site. To identify the Na3 binding site of GlyT2, we performed molecular dynamics (MD simulations. Surprisingly, a Na+ placed at the location consistent with the Na1' site of BetP spontaneously dissociated from its initial location and bound instead to a novel Na3 site. Using a combination of MD simulations of a comparative model of GlyT2 together with an analysis of the functional properties of wild type and mutant GlyTs we have identified an electrostatically favorable novel third Na+ binding site in GlyT2 formed by Trp263 and Met276 in TM3, Ala481 in TM6 and Glu648 in TM10.

  20. New insights into genotype–phenotype correlation for GLI3 mutations

    OpenAIRE

    Démurger, Florence; Ichkou, Amale; Mougou-Zerelli, Soumaya; Le Merrer, Martine; Goudefroye, Géraldine; Delezoide, Anne-Lise; Quélin, Chloé; Manouvrier, Sylvie; Baujat, Geneviève; Fradin, Mélanie; Pasquier, Laurent; Megarbané, André; Faivre, Laurence; Baumann, Clarisse; Nampoothiri, Sheela

    2014-01-01

    The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype–phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlightin...

  1. A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.

    Science.gov (United States)

    Falkenberg, K J; Newbold, A; Gould, C M; Luu, J; Trapani, J A; Matthews, G M; Simpson, K J; Johnstone, R W

    2016-07-01

    Vorinostat is an FDA-approved histone deacetylase inhibitor (HDACi) that has proven clinical success in some patients; however, it remains unclear why certain patients remain unresponsive to this agent and other HDACis. Constitutive STAT (signal transducer and activator of transcription) activation, overexpression of prosurvival Bcl-2 proteins and loss of HR23B have been identified as potential biomarkers of HDACi resistance; however, none have yet been used to aid the clinical utility of HDACi. Herein, we aimed to further elucidate vorinostat-resistance mechanisms through a functional genomics screen to identify novel genes that when knocked down by RNA interference (RNAi) sensitized cells to vorinostat-induced apoptosis. A synthetic lethal functional screen using a whole-genome protein-coding RNAi library was used to identify genes that when knocked down cooperated with vorinostat to induce tumor cell apoptosis in otherwise resistant cells. Through iterative screening, we identified 10 vorinostat-resistance candidate genes that sensitized specifically to vorinostat. One of these vorinostat-resistance genes was GLI1, an oncogene not previously known to regulate the activity of HDACi. Treatment of vorinostat-resistant cells with the GLI1 small-molecule inhibitor, GANT61, phenocopied the effect of GLI1 knockdown. The mechanism by which GLI1 loss of function sensitized tumor cells to vorinostat-induced apoptosis is at least in part through interactions with vorinostat to alter gene expression in a manner that favored apoptosis. Upon GLI1 knockdown and vorinostat treatment, BCL2L1 expression was repressed and overexpression of BCL2L1 inhibited GLI1-knockdown-mediated vorinostat sensitization. Taken together, we present the identification and characterization of GLI1 as a new HDACi resistance gene, providing a strong rationale for development of GLI1 inhibitors for clinical use in combination with HDACi therapy.

  2. GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1.

    Science.gov (United States)

    Inaguma, Shingo; Riku, Miho; Hashimoto, Mitsuyoshi; Murakami, Hideki; Saga, Shinsuke; Ikeda, Hiroshi; Kasai, Kenji

    2013-12-15

    The mismatch repair (MMR) system is indispensable for the fidelity of DNA replication, the impairment of which predisposes to the development and progression of many types of cancers. To date, GLI1 transcription factor, a key molecule of the Hedgehog signaling pathway, has been shown to regulate the expression of several genes crucial for a variety of cancer cell properties in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), but whether GLI1 could control the MMR system was not known. Here, we showed that GLI1 and GLI2 indirectly suppressed the expression of MLH1 in PDAC cells. Through GLI1 target gene screening, we found that GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41/DEC2/SHARP1 through a GLI-binding site in the promoter. Consistent with a previous report that BHLHE41 suppresses the MLH1 promoter activity, we found that the activation of GLI1 led to the BHLHE41-dependent suppression of MLH1, and a double knockdown of GLI1 and GLI2 conversely increased the MLH1 protein in PDAC cells. Using TALEN-based modification of the MLH1 gene, we further showed that GLI1 expression was indeed associated with an increased tolerance to a methylating agent, methylnitrosourea cooperatively with a lower copy number status of MLH1. Finally, GLI1 expression was immunohistochemically related positively with BHLHE41 and inversely with MLH1 in PDAC cells and precancerous lesions of the pancreas. On the basis of these results, we propose that GLI1 depresses the MMR activity and might contribute to the development and progression of PDAC. ©2013 AACR.

  3. The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification.

    Science.gov (United States)

    Yoshida, Michiko; Hata, Kenji; Takashima, Rikako; Ono, Koichiro; Nakamura, Eriko; Takahata, Yoshifumi; Murakami, Tomohiko; Iseki, Sachiko; Takano-Yamamoto, Teruko; Nishimura, Riko; Yoneda, Toshiyuki

    2015-03-26

    Indian hedgehog (Ihh) regulates endochondral ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2. However, the molecular mechanisms underlying these processes remain elusive. Here by using in vivo microarray analysis, we identify forkhead box C1 (Foxc1) as a transcriptional partner of Gli2. Foxc1 stimulates expression of Ihh target genes, including PTHrP and Col10a1, through its physical and functional interaction with Gli2. Conversely, a dominant negative Foxc1 inhibits the Ihh target gene expression. In a spontaneous loss of Foxc1 function mouse (Foxc1(ch/ch)), endochondral ossification is delayed and the expression of Ihh target genes inhibited. Moreover, the pathological Foxc1 missense mutation observed in the Axenfeld-Rieger syndrome impairs Gli2-Foxc1 association as well as Ihh function. Our findings suggest that Foxc1 is an important transcriptional partner of Ihh-Gli2 signalling during endochondral ossification, and that disruption of the Foxc1-Gli2 interaction causes skeletal abnormalities observed in the Axenfeld-Rieger syndrome.

  4. Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

    Science.gov (United States)

    Wu, B W; Zhu, J; Shi, H M; Jin, B; Wen, Z C

    2017-08-07

    Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.

  5. Osservazioni cliniche ed anatomiche nella storia della neuropsicologia del linguaggio: gli studi pre-Broca

    Directory of Open Access Journals (Sweden)

    Claudio Luzzatti

    2013-08-01

    Full Text Available Clinical and Anatomical Observations in the History of Neurolinguistics: Studies Predating Paul Broca – Classical neurological and neuropsychological handbooks usually cite Paul Broca’s communication on the frontal lobes as the seat of articulated speech (1861 as the starting point in the history of the study of aphasia as. In their seminal study, Benton and Joynt (1960 have collected numerous observations of aphasic patients from the Greek, Latin Medieval and Renaissance medical tradition and from the eighteenth-century Enlightenment literature. In none of the reported cases, however, were the crucial elements of aphasia, that is, is, on the one hand the distinction between language deficits, conceptual damage and speech disorders and, on the other hand, the association with lesions of the left brain hemisphere – clearly identified. The first part of this article describes the work of Johannes Schenck and Johannes Jakob Wepfer, two medical scientists in the six-teenth and seventeenth century, whose studies are almost entirely unknown. Johannes Schenck (1530-1598 completed a collection of clinical observations including both reports from antiquity and from his contemporaries. In his first volume (Observationes medicae de capite humano, Basel, 1584 he considers the major diseases of the head and face. At least 16 of these observations refer to patients with aphasia. Johannes Jakob Wepfer (1620-1695 published several texts on neuroanatomy, brain vascularization and apoplexy. He gathered a collection of neurological cases (Observationes medico-practicae de affectibus capitis internis & externis, which was published posthumously. At least 15 of the 222 observations included report the presence of aphasia. As expected, in almost all cases, aphasia was due to lesions in the left hemisphere. Wepfer, however, does not seem to have noted this asymmetry. In the second part of this article, the extraordinary study of Jean-Baptiste Bouillaud (1825 will be reported: Bouillaud outlined the basic principles of anatomo-functional correlations in neuropsychology and applied these principles in order to confirm empirically the role of the frontal lobes in language and speech production.

  6. Inserti abusivi e attribuzioni indifendibili. Spigolando tra gli unica del canzoniere provenzale Sg

    Directory of Open Access Journals (Sweden)

    Giuseppe Tavani

    2015-05-01

    Full Text Available The central section of the Occitan songbook kept at the Biblioteca de Catalunya (ms. 146, generally known as Sg since it originally came from Saragossa (from Gil y Gil’s library, continues to prove to be of great interest for the study of the reception of troubadour poetry in Catalan milieux, at a time when a new poetic tradition was taking shape, influenced by the Toulouse tradition of the Consistori de la Gaia Sciensa. These particular circles and period naturally influenced the selection of authors and texts – with the resulting inclusions and exclusions – as well as the accompanying attributions. The latter may in part be due to a tradition that was already corrupt, but also, especially as far as the unica are concerned, to a form of mimetic parasitism, accompanied by a tendency for illicit inclusions in the case of some particular texts for which, as in previous articles, I have tried to point out the degree of ‘impertinence’ and to decide whether to add them to the list of suspects, to place them under interrogation, or – in the most clearly arbitrary cases – to simply remove them. This paper will focus on a planh attributed to Raimbaut de Vaqueiras (394,4a, which Sg shares with Ve-Ag, and on three unica which Sg alone attributes to Giraut de Borneil (242,18a; 52a; 69a.

  7. Gli strumenti per la valutazione soggettiva del rischio stress lavoro-correlato

    DEFF Research Database (Denmark)

    Conway, Paul Maurice

    2009-01-01

    The instruments for subjective assessment of work-related stress are aimed to evaluate individual perceptions of aspects that are crucial in the causal process linking psychosocial exposure to harmful physical and psychological health effects. Subjective assessment is most commonly performed...... of the above-mentioned instruments are depicted. Finally, important aspects relating to the usage of self-administered questionnaires are emphasized, mainly when field evaluations are undertaken in specific work contexts......., those that have been applied to a higher number of subjects in Italy are the Job Content Questionnaire, the Effort/Reward Imbalance Questionnaire, the Occupational Stress Indicator and the Multidimensional Questionnaire of Organizational Health. In this contribution, the main characteristics...

  8. GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion

    Directory of Open Access Journals (Sweden)

    Baosheng Huang

    2016-05-01

    Full Text Available Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS, especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl-3-(4'-phenylphenoxy propyl] sarcosine (NFPS in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO. The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO induction in rats, while, low dose of NFPS (L-NFPS exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal, a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

  9. Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase.

    Directory of Open Access Journals (Sweden)

    Satya Brata Routh

    2016-05-01

    Full Text Available D-aminoacyl-tRNA deacylase (DTD removes D-amino acids mischarged on tRNAs and is thus implicated in enforcing homochirality in proteins. Previously, we proposed that selective capture of D-aminoacyl-tRNA by DTD's invariant, cross-subunit Gly-cisPro motif forms the mechanistic basis for its enantioselectivity. We now show, using nuclear magnetic resonance (NMR spectroscopy-based binding studies followed by biochemical assays with both bacterial and eukaryotic systems, that DTD effectively misedits Gly-tRNAGly. High-resolution crystal structure reveals that the architecture of DTD's chiral proofreading site is completely porous to achiral glycine. Hence, L-chiral rejection is the only design principle on which DTD functions, unlike other chiral-specific enzymes such as D-amino acid oxidases, which are specific for D-enantiomers. Competition assays with elongation factor thermo unstable (EF-Tu and DTD demonstrate that EF-Tu precludes Gly-tRNAGly misediting at normal cellular concentrations. However, even slightly higher DTD levels overcome this protection conferred by EF-Tu, thus resulting in significant depletion of Gly-tRNAGly. Our in vitro observations are substantiated by cell-based studies in Escherichia coli that show that overexpression of DTD causes cellular toxicity, which is largely rescued upon glycine supplementation. Furthermore, we provide direct evidence that DTD is an RNA-based catalyst, since it uses only the terminal 2'-OH of tRNA for catalysis without the involvement of protein side chains. The study therefore provides a unique paradigm of enzyme action for substrate selection/specificity by DTD, and thus explains the underlying cause of DTD's activity on Gly-tRNAGly. It also gives a molecular and functional basis for the necessity and the observed tight regulation of DTD levels, thereby preventing cellular toxicity due to misediting.

  10. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Science.gov (United States)

    Shahi, Mehdi Hayat; Holt, Roseline; Rebhun, Robert B

    2014-01-01

    The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  11. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  12. Abrogation of Gli3 expression suppresses the growth of colon cancer cells via activation of p53

    International Nuclear Information System (INIS)

    Kang, Han Na; Oh, Sang Cheul; Kim, Jun Suk; Yoo, Young A.

    2012-01-01

    p53, the major human tumor suppressor, appears to be related to sonic hedgehog (Shh)–Gli-mediated tumorigenesis. However, the role of p53 in tumor progression by the Shh–Gli signaling pathway is poorly understood. Herein we investigated the critical regulation of Gli3–p53 in tumorigenesis of colon cancer cells and the molecular mechanisms underlying these effects. RT-PCR analysis indicated that the mRNA level of Shh and Gli3 in colon tumor tissues was significantly higher than corresponding normal tissues (P < 0.001). The inhibition of Gli3 by treatment with Gli3 siRNA resulted in a clear decrease in cell proliferation and enhanced the level of expression of p53 proteins compared to treatment with control siRNA. The half-life of p53 was dramatically increased by treatment with Gli3 siRNA. In addition, treatment with MG132 blocked MDM2-mediated p53 ubiquitination and degradation, and led to accumulation of p53 in Gli3 siRNA-overexpressing cells. Importantly, ectopic expression of p53 siRNA reduced the ability of Gli3 siRNA to suppress proliferation of those cells compared with the cells treated with Gli3 siRNA alone. Moreover, Gli3 siRNA sensitized colon cancer cells to treatment with anti-cancer agents (5-FU and bevacizumab). Taken together, our studies demonstrate that loss of Gli3 signaling leads to disruption of the MDM2–p53 interaction and strongly potentiate p53-dependent cell growth inhibition in colon cancer cells, indicating a basis for the rational use of Gli3 antagonists as a novel treatment option for colon cancer.

  13. Codon 201Gly Polymorphic Type of the DCC Gene is Related to Disseminated Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Xiao-Tang Kong

    2001-01-01

    Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

  14. Steroidal regulation of Ihh and Gli1 expression in the rat uterus.

    Science.gov (United States)

    Kubota, Kaiyu; Yamauchi, Nobuhiko; Yamagami, Kazuki; Nishimura, Sho; Gobaru, Takafumi; Yamanaka, Ken-ichi; Wood, Chris; Soh, Tomoki; Takahashi, Masashi; Hattori, Masa-aki

    2010-05-01

    Ovarian steroid hormones, progesterone (P4), and estradiol (E2) strictly regulate the endometrial tissue remodeling required for successful embryo implantation. Indian hedgehog (Ihh) is up-regulated by P4 and critically mediates uterine receptivity in the mouse. However, the regulation of Ihh expression during the implantation period still remains unclear. The present study was conducted to elucidate the mechanism of the steroidal regulation in the expression of Ihh and Gli1, the mediator of the Ihh pathway. Ihh mRNA was expressed in the rat uterus on 3.5-5.5 days post-coitus (dpc), while Gli1 expression transiently increased at 3.5 dpc but decreased significantly on 5.5 dpc (P Ihh was induced by the implantation-induced E2 treatment in the primed rat uterus. In contrast, expression of Gli1 was significantly decreased by E2 treatment (P = 0.016). In the case of ICI182.780 (ICI) treatment, Ihh expression was eliminated by ICI, whilst Gli1 expression increased. These results suggest that Ihh expression is maintained at a high level until the initiation of implantation, while the expression of Gli1 is decreased just prior to the initiation of implantation depending on the E2 action. This observation aids in the understanding of the Ihh signaling pathway mediating uterine remodeling for implantation.

  15. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    International Nuclear Information System (INIS)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas; Astorga-Wells, Juan; Zubarev, Roman A.; Del Campo, Mark; Criswell, Angela R.; Sanctis, Daniele de; Jovine, Luca; Toftgård, Rune

    2013-01-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics

  16. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden); Astorga-Wells, Juan [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Biomotif AB, Enhagsvägen 7, SE-182 12 Danderyd (Sweden); Zubarev, Roman A. [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Del Campo, Mark; Criswell, Angela R. [Rigaku Americas Corporation, 9009 New Trails Drive, The Woodlands, TX 77381 (United States); Sanctis, Daniele de [European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, 38043 Grenoble (France); Jovine, Luca, E-mail: luca.jovine@ki.se; Toftgård, Rune, E-mail: luca.jovine@ki.se [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden)

    2013-12-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.

  17. Regulation of Calvarial Osteogenesis by Concomitant De-repression of GLI3 and Activation of IHH Targets

    OpenAIRE

    Lotta K. Veistinen; Tuija Mustonen; Tuija Mustonen; Md. Rakibul Hasan; Maarit Takatalo; Yukiho Kobayashi; Yukiho Kobayashi; Dörthe A. Kesper; Andrea Vortkamp; David P. Rice; David P. Rice

    2017-01-01

    Loss-of-function mutations in GLI3 and IHH cause craniosynostosis and reduced osteogenesis, respectively. In this study, we show that Ihh ligand, the receptor Ptch1 and Gli transcription factors are differentially expressed in embryonic mouse calvaria osteogenic condensations. We show that in both Ihh−/− and Gli3Xt−J/Xt−J embryonic mice, the normal gene expression architecture is lost and this results in disorganized calvarial bone development. RUNX2 is a master regulatory transcription facto...

  18. La crisi del diritto del lavoro

    Directory of Open Access Journals (Sweden)

    Alessandro Garilli

    2012-01-01

    Full Text Available Riassunto - L’Autore ripercorre in chiave critica l’evoluzione delle politiche legislative in materia di lavoro, alla luce dell’attuale fase di crisi economico finanziaria. Nell’esaminare i principali interventi normativi attuati da inizio secolo, l’Autore mette in evidenza le scelte di metodo e gli elementi di continuità che accomunano i vari provvedimenti, individuandoli nell’affannosa ricerca del punto di equilibrio tra flessibilità e garantismo. La riflessione si chiude con alcuni interrogativi sulle ultime linee di riforma del mercato del lavoro e con l’auspicio che, anche al cospetto delle imprescindibili ragioni dell’economia, il diritto del lavoro possa continuare a svolgere il proprio tradizionale ruolo di disciplina di tutela della persona.   Abstract - The author analyzes, with a critically oriented approach, the development of the employment law, in the light of the current economic and financial crisis. In examining the main regulatory measures implemented since the beginning of the century, the author highlights the methodological choices and the elements of continuity that unite the various measures, focusing them in a hard research of a point of balance between flexibility and security. The discussion concludes with some questions about the last lines of the reform of the labor market and with the hope that, even in the face of compelling reasons of economy, labor law can continue to play its traditional role of governing the protection of person.

  19. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V; Salic, Adrian

    2010-10-18

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu-Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a process inhibited by PKA.

  20. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V.

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu–Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu–Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu–Gli complexes, a process inhibited by PKA. PMID:20956384

  1. Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway.

    Directory of Open Access Journals (Sweden)

    Zhonglu Peng

    Full Text Available Hedgehog signaling pathway plays a critical role in the initiation and development of pancreatic ductal adenocarcinoma (PDA and represents an attractive target for PDA treatment. Lithium, a clinical mood stabilizer for mental disorders, potently inhibits the activity of glycogen synthase kinase 3β (GSK3β that promotes the ubiquitin-dependent proteasome degradation of GLI1, an important downstream component of hedgehog signaling. Herein, we report that lithium inhibits cell proliferation, blocks G1/S cell-cycle progression, induces cell apoptosis and suppresses tumorigenic potential of PDA cells through down-regulation of the expression and activity of GLI1. Moreover, lithium synergistically enhances the anti-cancer effect of gemcitabine. These findings further our knowledge of mechanisms of action for lithium and provide a potentially new therapeutic strategy for PDA through targeting GLI1.

  2. Mutation of the conserved Gly94 and Gly126 in elongation factor Tu from Escherichia coli. Elucidation of their structural and functional roles

    DEFF Research Database (Denmark)

    Knudsen, Charlotte Rohde; Kjaersgård, I V; Wiborg, O

    1995-01-01

    All guanine-nucleotide-binding proteins cycle between an inactive, GDP-bound and an active, GTP-bound conformation whereby they function as molecular switches. Elongation factor Tu from Escherichia coli is used as a model for defining residues important in the switch mechanism. Gly94 and Gly126...... were separately mutated to alanine residues to study their role in the switch mechanism. The mutant proteins are denoted [G94A]EF-Tu and [G126A]EF-Tu, respectively. Both mutations affect the affinities for guanine nucleotides considerably, resulting in a decrease in the characteristic preference...... for GDP over GTP. Furthermore the [G94A]EF-Tu mutant possesses an increased GTPase activity. The aminoacyl-tRNA affinity is much reduced for [G94A]EF-Tu, as reflected in an increase of the dissociation rate constant for the ternary complex by a factor of 40. Surprisingly, however, both mutants...

  3. Covalent attachment of cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) to poly(etheretherketone) surface by tailored silanization layers technique

    International Nuclear Information System (INIS)

    Zheng, Yanyan; Xiong, Chengdong; Li, Xiaoyu; Zhang, Lifang

    2014-01-01

    Highlights: • The carbonyl groups on PEEK surface were effectively reduced to hydroxyl groups using sodium borohydride. • Silanization layers technique was employed to immobilize the cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) on hydroxylation-pretreated PEEK sheet surface by covalent chemical attachment. • XPS, surface profiler and water contact angle measurements proved the presence of GRGD on PEEK surface. • Osteoblast-like cells (MC3T3-E1) attachment and proliferation were improved effectively on GRGD-modified PEEK surface. - Abstract: Poly(etheretherketone) (PEEK) is a rigid semicrystalline polymer that combines excellent mechanical properties, broad chemical resistance and bone-like stiffness and is widely used in biomedical fields. However, PEEK is naturally bioinert, leading to limited biomedical applications, especially when a direct bone-implant osteointegration is desired. In this study, a three-step reaction procedure was employed to immobilize the cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) on the surface of PEEK sheet by covalent chemical attachment to favor cell adhesion and proliferation. First, hydroxylation-pretreated PEEK surfaces were silanized with 7-Oct-1-enyltrichlorosilane (OETS) in dry cyclohexane, resulting in a silanization layer with terminal ethenyl. Second, the terminal ethylenic double bonds of the silanization layer on PEEK surface were converted to carboxyl groups through acidic potassium manganate oxidation. Finally, GRGD was covalently attached by carbodiimide mediated condensation between the carboxyl on PEEK surface and amine presents in GRGD. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, surface profiler and water contact angle measurements were applied to characterize the modified surfaces. The effect of cells attachment and proliferation on each specimen was investigated. Pre-osteoblast cells (MC3T3-E1) attachment, spreading and proliferation

  4. GlyGly-CTERM and rhombosortase: a C-terminal protein processing signal in a many-to-one pairing with a rhomboid family intramembrane serine protease.

    Directory of Open Access Journals (Sweden)

    Daniel H Haft

    Full Text Available The rhomboid family of serine proteases occurs in all domains of life. Its members contain at least six hydrophobic membrane-spanning helices, with an active site serine located deep within the hydrophobic interior of the plasma membrane. The model member GlpG from Escherichia coli is heavily studied through engineered mutant forms, varied model substrates, and multiple X-ray crystal studies, yet its relationship to endogenous substrates is not well understood. Here we describe an apparent membrane anchoring C-terminal homology domain that appears in numerous genera including Shewanella, Vibrio, Acinetobacter, and Ralstonia, but excluding Escherichia and Haemophilus. Individual genomes encode up to thirteen members, usually homologous to each other only in this C-terminal region. The domain's tripartite architecture consists of motif, transmembrane helix, and cluster of basic residues at the protein C-terminus, as also seen with the LPXTG recognition sequence for sortase A and the PEP-CTERM recognition sequence for exosortase. Partial Phylogenetic Profiling identifies a distinctive rhomboid-like protease subfamily almost perfectly co-distributed with this recognition sequence. This protease subfamily and its putative target domain are hereby renamed rhombosortase and GlyGly-CTERM, respectively. The protease and target are encoded by consecutive genes in most genomes with just a single target, but far apart otherwise. The signature motif of the Rhombo-CTERM domain, often SGGS, only partially resembles known cleavage sites of rhomboid protease family model substrates. Some protein families that have several members with C-terminal GlyGly-CTERM domains also have additional members with LPXTG or PEP-CTERM domains instead, suggesting there may be common themes to the post-translational processing of these proteins by three different membrane protein superfamilies.

  5. Covalent attachment of cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) to poly(etheretherketone) surface by tailored silanization layers technique

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yanyan [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xiong, Chengdong [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Zhang, Lifang, E-mail: zhanglfcioc@163.com [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China)

    2014-11-30

    Highlights: • The carbonyl groups on PEEK surface were effectively reduced to hydroxyl groups using sodium borohydride. • Silanization layers technique was employed to immobilize the cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) on hydroxylation-pretreated PEEK sheet surface by covalent chemical attachment. • XPS, surface profiler and water contact angle measurements proved the presence of GRGD on PEEK surface. • Osteoblast-like cells (MC3T3-E1) attachment and proliferation were improved effectively on GRGD-modified PEEK surface. - Abstract: Poly(etheretherketone) (PEEK) is a rigid semicrystalline polymer that combines excellent mechanical properties, broad chemical resistance and bone-like stiffness and is widely used in biomedical fields. However, PEEK is naturally bioinert, leading to limited biomedical applications, especially when a direct bone-implant osteointegration is desired. In this study, a three-step reaction procedure was employed to immobilize the cell-adhesive peptide Gly-Arg-Gly-Asp (GRGD) on the surface of PEEK sheet by covalent chemical attachment to favor cell adhesion and proliferation. First, hydroxylation-pretreated PEEK surfaces were silanized with 7-Oct-1-enyltrichlorosilane (OETS) in dry cyclohexane, resulting in a silanization layer with terminal ethenyl. Second, the terminal ethylenic double bonds of the silanization layer on PEEK surface were converted to carboxyl groups through acidic potassium manganate oxidation. Finally, GRGD was covalently attached by carbodiimide mediated condensation between the carboxyl on PEEK surface and amine presents in GRGD. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, surface profiler and water contact angle measurements were applied to characterize the modified surfaces. The effect of cells attachment and proliferation on each specimen was investigated. Pre-osteoblast cells (MC3T3-E1) attachment, spreading and proliferation

  6. GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors.

    Directory of Open Access Journals (Sweden)

    Jay Joo

    2009-10-01

    Full Text Available The Ewing Sarcoma Family Tumors (ESFT consist of the classical pathologic entities of Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor. Occurring largely in the childhood through young adult years, these tumors have an unsurpassed propensity for metastasis and have no defined cell of origin. The biology of these aggressive malignancies centers around EWS/FLI1 and related EWS/ETS chimeric transcription factors, which are largely limited to this tumor class. Much progress has been made in the identification of a network of loci whose expression is modulated by EWS/FLI1 and its congeners. To date, little progress has been made in reconstructing the sequence of direct and indirect events that produce this network of modulated loci. The recent identification of GLI1 as an upregulated target of EWS/ETS transcription factors suggests a target which may be a more central mediator in the ESFT signaling network. In this paper, we further define the relationship of EWS/FLI1 expression and GLI1 upregulation in ESFT. This relationship is supported with data from primary tumor specimens. It is consistently observed across multiple ESFT cell lines and with multiple means of EWS/FLI1 inhibition. GLI1 inhibition affects tumor cell line phenotype whether shRNA or endogenous or pharmacologic inhibitors are employed. As is seen in model transformation systems, GLI1 upregulation by EWS/FLI1 appears to be independent of Hedgehog stimulation. Consistent with a more central role in ESFT pathogenesis, several known EWS/FLI1 targets appear to be targeted through GLI1. These findings further establish a central role for GLI1 in the pathogenesis of Ewing Tumors.

  7. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

    Directory of Open Access Journals (Sweden)

    Alexandre N Ermilov

    2016-11-01

    Full Text Available For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings

  8. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

    Science.gov (United States)

    Ermilov, Alexandre N; Kumari, Archana; Li, Libo; Joiner, Ariell M; Grachtchouk, Marina A; Allen, Benjamin L; Dlugosz, Andrzej A; Mistretta, Charlotte M

    2016-11-01

    For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste

  9. Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

    2012-09-01

    The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

  10. The transcription factor GLI1 modulates the inflammatory response during pancreatic tissue remodeling.

    Science.gov (United States)

    Mathew, Esha; Collins, Meredith A; Fernandez-Barrena, Maite G; Holtz, Alexander M; Yan, Wei; Hogan, James O; Tata, Zachary; Allen, Benjamin L; Fernandez-Zapico, Martin E; di Magliano, Marina Pasca

    2014-10-03

    Pancreatic cancer, one of the deadliest human malignancies, is almost uniformly associated with a mutant, constitutively active form of the oncogene Kras. Studies in genetically engineered mouse models have defined a requirement for oncogenic KRAS in both the formation of pancreatic intraepithelial neoplasias, the most common precursor lesions to pancreatic cancer, and in the maintenance and progression of these lesions. Previous work using an inducible model allowing tissue-specific and reversible expression of oncogenic Kras in the pancreas indicates that inactivation of this GTPase at the pancreatic intraepithelial neoplasia stage promotes pancreatic tissue repair. Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway, as a central player in pancreatic tissue repair upon Kras inactivation. Deletion of a single allele of Gli1 results in improper stromal remodeling and perdurance of the inflammatory infiltrate characteristic of pancreatic tumorigenesis. Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and the recruitment of immune cells that are vital for tissue recovery. Analysis of the mechanism using expression and chromatin immunoprecipitation assays identified a subset of cytokines, including IL-6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon. Finally, we demonstrate that canonical Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery. Collectively, these data delineate a new pathway controlling tissue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment during this cellular process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation.

    Science.gov (United States)

    Koziel, Lydia; Wuelling, Manuela; Schneider, Sabine; Vortkamp, Andrea

    2005-12-01

    During endochondral ossification, the secreted growth factor Indian hedgehog (Ihh) regulates several differentiation steps. It interacts with a second secreted factor, parathyroid hormone-related protein (PTHrP), to regulate the onset of hypertrophic differentiation, and it regulates chondrocyte proliferation and ossification of the perichondrium independently of PTHrP. To investigate how the Ihh signal is translated in the different target tissues, we analyzed the role of the zinc-finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs. Loss of Gli3 in Ihh mutants restores chondrocyte proliferation and delays the accelerated onset of hypertrophic differentiation observed in Ihh-/- mutants. Furthermore the expression of the Ihh target genes patched (Ptch) and PTHrP is reactivated in Ihh-/-;Gli3-/- mutants. Gli3 seems thus to act as a strong repressor of Ihh signals in regulating chondrocyte differentiation. In addition, loss of Gli3 in mice that overexpress Ihh in chondrocytes accelerates the onset of hypertrophic differentiation by reducing the domain and possibly the level of PTHrP expression. Careful analysis of chondrocyte differentiation in Gli3-/- mutants revealed that Gli3 negatively regulates the differentiation of distal, low proliferating chondrocytes into columnar, high proliferating cells. Our results suggest a model in which the Ihh/Gli3 system regulates two distinct steps of chondrocyte differentiation: (1) the switch from distal into columnar chondrocytes is repressed by Gli3 in a PTHrP-independent mechanism; (2) the transition from proliferating into hypertrophic chondrocytes is regulated by Gli3-dependent expression of PTHrP. Furthermore, by regulating distal chondrocyte differentiation, Gli3 seems to position the domain of PTHrP expression.

  12. Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

    Science.gov (United States)

    Liu, Jessica Ai-Jia; Lai, Frank Pui-Ling; Gui, Hong-Sheng; Sham, Mai-Har; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Hui, Chi-Chung; Ngan, Elly Sau-Wai

    2015-12-01

    Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis. We performed deep-target sequencing of DNA from 20 patients with Hirschsprung disease (16 men, 4 women), and 20 individuals without (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10. Biological effects of GLI mutations were tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Δ699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using time-lapse imaging. We identified 3 mutations in GLI in 5 patients with Hirschsprung disease but no controls; all lead to increased transcription of SOX10 in cell lines. SUFU, GLI, and SOX10 form a regulatory loop that controls the neuronal vs glial lineages and migration of NCCs. Sufu mutants mice had high Gli activity, due to loss of Sufu, disrupting the regulatory loop and migration of enteric NCCs, leading to defective axonal fasciculation, delayed gut colonization, or intestinal hypoganglionosis. The ratio of enteric neurons to glia correlated inversely with Gli activity. We identified mutations that increase GLI activity in patients with Hirschsprung disease. Disruption of the SUFU-GLI-SOX10 regulatory loop disrupts migration of NCCs and development of the enteric nervous system in mice. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Il danno alla persona del lavoratore: il mobbing orizzontale

    Directory of Open Access Journals (Sweden)

    Riccardo Gentile

    2011-12-01

    Full Text Available Sommario:1. Il mobbing tra diritto civile e diritto del lavoro – 2. Il fenomeno mobbing: gli studi iniziali e la definizione – 3. Le concrete condotte integranti fattispecie di mobbing – 4. Onere della prova – 5. Il mobbing orizzontale – 6. L’elemento soggettivo di colpevolezza del da­tore di lavoro nella responsabilità ex art. 2087 c.c. per mobbing orizzontale

  14. PKC-Dependent GlyT1 Ubiquitination Occurs Independent of Phosphorylation: Inespecificity in Lysine Selection for Ubiquitination.

    Directory of Open Access Journals (Sweden)

    Susana P Barrera

    Full Text Available Neurotransmitter transporter ubiquitination is emerging as the main mechanism for endocytosis and sorting of cargo into lysosomes. In this study, we demonstrate PKC-dependent ubiquitination of three different isoforms of the glycine transporter 1 (GlyT1. Incubation of cells expressing transporter with the PKC activator phorbol ester induced a dramatic, time-dependent increase in GlyT1 ubiquitination, followed by accumulation of GlyT1 in EEA1 positive early endosomes. This occurred via a mechanism that was abolished by inhibition of PKC. GlyT1 endocytosis was confirmed in both retinal sections and primary cultures of mouse amacrine neurons. Replacement of only all lysines in the N-and C-termini to arginines prevented ubiquitination and endocytosis, displaying redundancy in the mechanism of ubiquitination. Interestingly, a 40-50% reduction in glycine uptake was detected in phorbol-ester stimulated cells expressing the WT-GlyT1, whereas no significant change was for the mutant protein, demonstrating that endocytosis participates in the reduction of uptake. Consistent with previous findings for the dopamine transporter DAT, ubiquitination of GlyT1 tails functions as sorting signal to deliver transporter into the lysosome and removal of ubiquitination sites dramatically attenuated the rate of GlyT1 degradation. Finally, we showed for the first time that PKC-dependent GlyT1 phosphorylation was not affected by removal of ubiquitination sites, suggesting separate PKC-dependent signaling events for these posttranslational modifications.

  15. Implications of the Transition From Zapletal to GLI Reference Values for Spirometry

    NARCIS (Netherlands)

    Raaijmakers, Lena; Zwitserloot, Annelies; Merkus, Peter; Gappa, Monika

    The current standard for monitoring lung function in children with asthma is spirometry. In Europe, results of these lung function tests have been related to Zapletal reference values published in 1977. Recently, the Global Lung Function Initiative (GLI) published predicted values of spirometry for

  16. Alpha-adducin Gly460Trp polymorphism and renal hemodynamics in essential hypertension

    NARCIS (Netherlands)

    Beeks, Esther; van der Klauw, Melanie M; Kroon, Abraham A; Spiering, Wilko; Fuss-Lejeune, Monique J M J; de Leeuw, Peter W

    2004-01-01

    Previous studies have shown an association between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. Not much is known about the effects of the variants of this polymorphism on renal hemodynamics and function. Therefore, we performed the present study to investigate the

  17. Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres

    DEFF Research Database (Denmark)

    Preston, Laura C; Lipscomb, Simon; Robinson, Paul

    2006-01-01

    We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined how this mutation, Gly159Asp, affects contractile regulation when incorporated into muscle fibres. Endogenous troponin in rabbit skinned...

  18. Stabilization of a chitinase from Serratia marcescens by Gly-->Ala and Xxx-->Pro mutations.

    NARCIS (Netherlands)

    Gaseidnes, S.; Synstad, B.; Jia, X.; Kjellesvik, H.; Vriend, G.; Eijsink, V.G.

    2003-01-01

    This paper describes attempts to increase the kinetic stability of chitinase B from Serratia marcescens (ChiB) by the introduction of semi-automatically designed rigidifying mutations of the Gly-->Ala and Xxx-->Pro type. Of 15 single mutants, several displayed significant increases in thermal

  19. GliZ, a transcriptional regulator of gliotoxin in Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Bok, J.W.; Chung, D.W.; Balajee, A.

    2006-01-01

    Gliotoxin is a nonribosomal peptide produced by Aspergillus fumigatus. This compound has been proposed as an A. fumigatus virulence factor due to its cytotoxic, genotoxic, and apoptotic properties. Recent identification of the gliotoxin gene cluster identified several genes (gli genes) likely inv...

  20. GLI1, a master regulator of the hallmark of pancreatic cancer.

    Science.gov (United States)

    Kasai, Kenji

    2016-12-01

    Hedgehog signaling is highly conserved across species and governs proper embryonic development. Germline gene mutations that reduce this signaling activity cause a variety of developmental abnormalities such as holoprosencephaly, while those that enhance Hedgehog signaling activity induce a tumor-predisposition condition Nevoid basal cell carcinoma syndrome. Furthermore, dysregulated activation of Hedgehog signaling has been recognized in various sporadic malignancies, including pancreatic adenocarcinoma. Pancreatic adenocarcinoma develops through a multistep carcinogenesis starting with oncogenic mutation of the KRAS gene. During this process, precancerous or cancer cells secrete Hedgehog ligand proteins to promote characteristic desmoplastic stroma around the cells, which in turn activates the expression of the downstream transcription factor GLI1 inside the cells. The quantitative and spatiotemporal dysregulation of GLI1 subsequently leads to the expression of transcriptional target genes of GLI1 that govern the hallmark of malignant properties. Here, after a brief introductory outline, a perspective is offered of Hedgehog signaling with a special focus on the role of GLI1 in pancreatic carcinogenesis. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  1. Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development.

    Science.gov (United States)

    Hilton, Matthew J; Tu, Xiaolin; Cook, Julie; Hu, Hongliang; Long, Fanxin

    2005-10-01

    Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key effectors of hedgehog signaling, it has not been established which Gli protein mediates Ihh activity in skeletal development. Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued the defects in osteoblast development and cartilage vascularization. Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteoblast development in perichondrial progenitor cells. Our results not only establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identify an osteogenic role for a vasculature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus chondrocyte fate in the mesenchymal progenitors.

  2. GLI1 is involved in cell cycle regulation and proliferation of NT2 embryonal carcinoma stem cells

    DEFF Research Database (Denmark)

    Vestergaard, Janni; Lind-Thomsen, Allan; Pedersen, Mikkel W.

    2008-01-01

    of altered HH signaling are interpreted by specific cell types. We have investigated the role of the HH transcription factor glioma-associated oncogene homolog 1 (GLI1) in the human Ntera2=D1 (NT2) embryonal carcinoma stem cell line. The study revealed that expression of GLI1 and its direct transcriptional......1 phase cyclins. In conclusion, our results suggest that GLI1 is involved in cell cycle and proliferation control in the embryonal carcinoma stem cell line NT2....... target Patched (PTCH) is downregulated in the early stages of retinoic acid-induced neuronal differentiation of NT2 cells. To identify transcriptional targets of the HH transcription factor GLI1 in NT2 cells, we performed global expression profiling following GLI1 RNA interference (RNAi). Of the similar...

  3. Una complessa chiarezza: gli ipertesti di Primo Levi

    Directory of Open Access Journals (Sweden)

    Tommaso Pepe

    2016-11-01

    Full Text Available Scrittore poliedrico e versatile, Primo Levi è stato anche un costruttore di estesi e articolati ipertesti: strutture macrotestuali fondate su legami e interrelazioni tese fra opere cronologicamente e tipologicamente differenziate. Un esempio straordinario, ma non certo isolato, di questa scrittura di secondo grado, organizzata in complessi palinsesti testuali, è quello che già Marco Belpoliti ha definito nei termini di «macrotesto del Lager»: un reticolo intra- e intertestuale che, a partire da Se questo è un uomo, si è sviluppato con un andamento rizomatico attraverso diverse stratificazioni scrittorie e genealogiche, sino a I sommersi e i salvati. Il «rizoma» tuttavia è semplicemente una delle varie macrostrutture individuabili nell’opera di Levi. Attraverso un confronto contrastivo con l’opera di Calvino, il saggio si propone di indagare alcune delle caratteristiche salienti di questa scrittura ipertestuale, mostrando come l’intensa sperimentazione scrittoria perseguita da Levi sia da ricollegarsi a una parallela svolta epistemologica, data dall’insorgere di quella che Edgar Morin ha definito come «sfida della complessità».Primo Levi can be considered a versatile and polyhedral writer, capable of building long and articulated hypertexts, i.e., macrotextual structures based on the links and interrelations among works which differ both from a chronological and typological point of view. An extraordinary, but certainly not isolated, example of this writing, organized according to complex textual palimpsests, is the one that Marco Belpoliti defined as the «macrotext of the Lager»: it is an intra- and intertextual network that, starting from If This is a Man, developed according to a rhizomatic structure through his different works and genealogical stratifications, ending with The Drowned and the Saved. The «rhizome», however, is only one of the different macrostructures which may be singled out in Levi’s work. By

  4. Poetiche del sublime. Il Coro di morti dalle Operette morali a Goffredo Petrassi

    Directory of Open Access Journals (Sweden)

    Giovanni Vito Distefano

    2018-01-01

    Full Text Available In un autore come Leopardi, incline al serio in misura apparentemente esclusiva e poco votato all’arte drammatica, è tuttavia in un piccolo capolavoro tragicomico che possono individuarsi le prime tracce di una moderna estetica del sublime. L’articolo propone innanzitutto una lettura in chiave metapoetica del Coro di morti, volta ad osservare la salda convergenza che nella scrittura leopardiana lega reciporcamente gli avanzamenti del pensiero – la verità di una condizione umana irresolubilmente e incomprensibilmente priva della felicità – e gli sviluppi attinenti al piano formale e a quello della riflessione filosofico-estetica – con la messa in discussione tanto della classicistica estetica della mimesis, quanto di quella romantica del sentimentale. Infine, nella seconda parte, il paradigma estetico del sublime fornirà i termini entro i quali tracciare una ricostruzione del procedimento adattivo che lega all’originale leopardiano la trasposizione musicale realizzata nel 1941 da Goffredo Petrassi.

  5. Oscillazioni del mesone D^0

    CERN Document Server

    Schiraldi, Vito; Morello, Michael Joseph

    In fisica delle particelle, con il termine di "oscillazione" si indica la trasformazione di una particella neutra nella sua antiparticella e viceversa, fenomeno dovuto al fatto che gli autostati di flavor non sono autostati della matrice di massa. Il Modello Standard delle interazioni fondamentali predice che l'oscillazione del mesone D^0 avvenga su tempi molto maggiori di una vita media, e appaia perciò come un effetto piccolo, inferiore al percento, in contrasto con il caso dei mesoni B^0 e B^0_s che oscillano con molta maggiore rapidità. Sperimentalmente, l'oscillazione dei mesoni D^0 è rimasta inosservata fino a tempi recenti: la prima evidenza sperimentale dell'esistenza di un effetto di oscillazione è stata ottenuta soltanto nella primavera del 2007 dagli esperimenti BaBar (SLAC, USA) e Belle (KEKB, Japan). Nell'agosto 2007 anche l’esperimento CDF (Fermilab, USA) ha presentato una evidenza simile, basata sull'analisi di una parte del campione di dati disponibile. La tesi descrive gli aspetti speri...

  6. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival

    International Nuclear Information System (INIS)

    Haaf, Anette ten; Bektas, Nuran; Serenyi, Sonja von; Losen, Inge; Arweiler, Elfriede Christel; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2009-01-01

    The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC) GLI1 expression was analysed in human invasive breast carcinomas (n = 229) in comparison to normal human breast tissues (n = 58). GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3) and tumourous breast cell lines (n = 8). IHC data were statistically interpreted using SPSS version 14.0. Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5) human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test). On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test) and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019), but also with higher tumour stage (P < 0.001) and an increased number of tumour-positive axillar lymph nodes (P = 0.027). Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of

  7. Gli effetti delle imposte sulla convenienza a detenere titoli pubblici in Italia (1974-1986. (The effects of taxes on the yields on government bonds in Italy

    Directory of Open Access Journals (Sweden)

    A. DI MAJO

    2013-12-01

    Full Text Available Nel 1974 l'Italia ha emanato una riforma fiscale che differenzia il trattamento fiscale per i detentori di obbligazioni a seconda che essi siano imprese o privati cittadini. A sua volta, il " reddito fisso " attività finanziarie sono state distinte in base alla natura dell'emittente , pubblico o privato . Il presente lavoro tenta di tracciare e valutare l'impatto di questa riforma . In particolare, le variazioni di rendimento sui titoli di Stato viene analizzata per gli anni successivi all'introduzione della riforma fino alla sua modifica più recente , realizzato nel mese di settembre 1986. a tal fine , gli autori riassumono la modifica apportata nel codice fiscale prima quantificazione del loro impatto , soprattutto con riferimento ai conti profitti e perdite di credito istituzioni. Alcune indicazioni sugli effetti della più recente modifica del trattamento fiscale degli interessi sono anche descritti In 1974 Italy enacted a tax reform that differentiated the tax treatment for bond holders according to whether they are businesses or private individuals. In turn, "fixed income” financial activities were distinguished based on the nature of the issuer, public or private. The present work attempts to trace and evaluate the impact of this reform. In particular, the changes in yield on government bonds is analysed for the years following the introduction of the reform up to its most recent change, made in September 1986. To this end, the authors summarise the change made in the tax code before quantifying their impact, mainly with reference to the profit and loss accounts of credit institutions. Some indications on the effects of the most recent change in the tax treatment of interest are also outlined.JEL: H20

  8. L’ipotesi del ciclo vitale, la politica fiscale e la previdenza sociale

    Directory of Open Access Journals (Sweden)

    Tullio Jappelli

    2005-06-01

    Full Text Available Il lavoro riassume le principali implicazioni dell’ipotesi del ciclo vitale per quanto riguarda il risparmio individuale e aggregato, la politica fiscale e la previdenza sociale, soffermandosi sui contributi più importanti di Modigliani su questi temi. Anche se non è facile conciliare alcuni risultati empirici recenti con l’ipotesi del ciclo vitale, soprattutto gli aspetti di inerzia, miopia e comportamento irrazionale documentati nella letteratura comportamentale, gli studi di Modigliani rappresentano ancora oggi la base di riferimento principale per studiare le decisioni dirisparmio individuali e per operare scelte di politica economica.

  9. The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick hair in Japanese men with androgenetic alopecia.

    Science.gov (United States)

    Iwabuchi, Tokuro; Takeda, Shunsuke; Yamanishi, Haruyo; Ideta, Ritsuro; Ehama, Ritsuko; Tsuruda, Akinori; Shibata, Hideaki; Ito, Tomoko; Komatsu, Nobuyuki; Terai, Keiko; Oka, Syuichi

    2016-06-01

    A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. This study focused on the ability of the peptide to promote human hair growth. We used a human hair keratinocyte proliferation assay and organ cultures of human hair follicle as in vitro systems. The lotions with and without the penta-peptide were administered to 22 Japanese men with androgenetic alopecia (AGA) for 4 months in a double-blind and randomized clinical study. The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μm (P baldness (P = 0.020) when blinded reviewers graded photographs of the participants according to a standardized baldness scale. No adverse dermatological effects due to treatment were noted during this clinical study. This penta-peptide promotes proliferation of human hair keratinocytes and hair shaft elongation of human hair follicles, in vitro. This peptide increases thick hair ratio in vivo, and this compound is useful for the improvement of AGA. © 2016 Wiley Periodicals, Inc.

  10. Identification and Validation of Novel Hedgehog-Responsive Enhancers Predicted by Computational Analysis of Ci/Gli Binding Site Density

    Science.gov (United States)

    Richards, Neil; Parker, David S.; Johnson, Lisa A.; Allen, Benjamin L.; Barolo, Scott; Gumucio, Deborah L.

    2015-01-01

    The Hedgehog (Hh) signaling pathway directs a multitude of cellular responses during embryogenesis and adult tissue homeostasis. Stimulation of the pathway results in activation of Hh target genes by the transcription factor Ci/Gli, which binds to specific motifs in genomic enhancers. In Drosophila, only a few enhancers (patched, decapentaplegic, wingless, stripe, knot, hairy, orthodenticle) have been shown by in vivo functional assays to depend on direct Ci/Gli regulation. All but one (orthodenticle) contain more than one Ci/Gli site, prompting us to directly test whether homotypic clustering of Ci/Gli binding sites is sufficient to define a Hh-regulated enhancer. We therefore developed a computational algorithm to identify Ci/Gli clusters that are enriched over random expectation, within a given region of the genome. Candidate genomic regions containing Ci/Gli clusters were functionally tested in chicken neural tube electroporation assays and in transgenic flies. Of the 22 Ci/Gli clusters tested, seven novel enhancers (and the previously known patched enhancer) were identified as Hh-responsive and Ci/Gli-dependent in one or both of these assays, including: Cuticular protein 100A (Cpr100A); invected (inv), which encodes an engrailed-related transcription factor expressed at the anterior/posterior wing disc boundary; roadkill (rdx), the fly homolog of vertebrate Spop; the segment polarity gene gooseberry (gsb); and two previously untested regions of the Hh receptor-encoding patched (ptc) gene. We conclude that homotypic Ci/Gli clustering is not sufficient information to ensure Hh-responsiveness; however, it can provide a clue for enhancer recognition within putative Hedgehog target gene loci. PMID:26710299

  11. Regulation of Calvarial Osteogenesis by Concomitant De-repression of GLI3 and Activation of IHH Targets

    Directory of Open Access Journals (Sweden)

    Lotta K. Veistinen

    2017-12-01

    Full Text Available Loss-of-function mutations in GLI3 and IHH cause craniosynostosis and reduced osteogenesis, respectively. In this study, we show that Ihh ligand, the receptor Ptch1 and Gli transcription factors are differentially expressed in embryonic mouse calvaria osteogenic condensations. We show that in both Ihh−/− and Gli3Xt−J/Xt−J embryonic mice, the normal gene expression architecture is lost and this results in disorganized calvarial bone development. RUNX2 is a master regulatory transcription factor controlling osteogenesis. In the absence of Gli3, RUNX2 isoform II and IHH are upregulated, and RUNX2 isoform I downregulated. This is consistent with the expanded and aberrant osteogenesis observed in Gli3Xt−J/Xt−J mice, and consistent with Runx2-I expression by relatively immature osteoprogenitors. Ihh−/− mice exhibited small calvarial bones and HH target genes, Ptch1 and Gli1, were absent. This indicates that IHH is the functional HH ligand, and that it is not compensated by another HH ligand. To decipher the roles and potential interaction of Gli3 and Ihh, we generated Ihh−/−;Gli3Xt−J/Xt−J compound mutant mice. Even in the absence of Ihh, Gli3 deletion was sufficient to induce aberrant precocious ossification across the developing suture, indicating that the craniosynostosis phenotype of Gli3Xt−J/Xt−J mice is not dependent on IHH ligand. Also, we found that Ihh was not required for Runx2 expression as the expression of RUNX2 target genes was unaffected by deletion of Ihh. To test whether RUNX2 has a role upstream of IHH, we performed RUNX2 siRNA knock down experiments in WT calvarial osteoblasts and explants and found that Ihh expression is suppressed. Our results show that IHH is the functional HH ligand in the embryonic mouse calvaria osteogenic condensations, where it regulates the progression of osteoblastic differentiation. As GLI3 represses the expression of Runx2-II and Ihh, and also elevates the Runx2-I expression

  12. Regulation of Calvarial Osteogenesis by Concomitant De-repression of GLI3 and Activation of IHH Targets.

    Science.gov (United States)

    Veistinen, Lotta K; Mustonen, Tuija; Hasan, Md Rakibul; Takatalo, Maarit; Kobayashi, Yukiho; Kesper, Dörthe A; Vortkamp, Andrea; Rice, David P

    2017-01-01

    Loss-of-function mutations in GLI3 and IHH cause craniosynostosis and reduced osteogenesis, respectively. In this study, we show that Ihh ligand, the receptor Ptch1 and Gli transcription factors are differentially expressed in embryonic mouse calvaria osteogenic condensations. We show that in both Ihh -/- and Gli3 Xt - J / Xt - J embryonic mice, the normal gene expression architecture is lost and this results in disorganized calvarial bone development. RUNX2 is a master regulatory transcription factor controlling osteogenesis. In the absence of Gli3 , RUNX2 isoform II and IHH are upregulated, and RUNX2 isoform I downregulated. This is consistent with the expanded and aberrant osteogenesis observed in Gli3 Xt - J / Xt - J mice, and consistent with Runx2-I expression by relatively immature osteoprogenitors. Ihh -/- mice exhibited small calvarial bones and HH target genes, Ptch1 and Gli1 , were absent. This indicates that IHH is the functional HH ligand, and that it is not compensated by another HH ligand. To decipher the roles and potential interaction of Gli3 and Ihh, we generated Ihh -/- ; Gli3 Xt - J / Xt - J compound mutant mice. Even in the absence of Ihh, Gli3 deletion was sufficient to induce aberrant precocious ossification across the developing suture, indicating that the craniosynostosis phenotype of Gli3 Xt - J / Xt - J mice is not dependent on IHH ligand. Also, we found that Ihh was not required for Runx2 expression as the expression of RUNX2 target genes was unaffected by deletion of Ihh . To test whether RUNX2 has a role upstream of IHH, we performed RUNX2 siRNA knock down experiments in WT calvarial osteoblasts and explants and found that Ihh expression is suppressed. Our results show that IHH is the functional HH ligand in the embryonic mouse calvaria osteogenic condensations, where it regulates the progression of osteoblastic differentiation. As GLI3 represses the expression of Runx2-II and Ihh , and also elevates the Runx2-I expression, and as IHH

  13. IL FILM A LEZIONE DI ITALIANO L2: GLI ESAMI AL CINEMA

    Directory of Open Access Journals (Sweden)

    Michela Albizzati

    2014-02-01

    Full Text Available Può il film rivelarsi uno strumento utile a lezione di italiano L2? Quali sono i limiti ed i vantaggi dell’utilizzo di materiale audiovisivo autentico in aula? Come strutturare un’attività basata sulla visione di un film italiano in lingua originale? Quali strategie mette in atto l’apprendente per comprendere un film nella L2? “Il film a lezione di italiano L2: gli esami al cinema” cerca di rispondere a queste domande attraverso una riflessione sull’utilità del cinema a lezione e proponendo un’attività didattica basata sulla visione di sequenze tratte da film italiani. Considerando la pellicola come documento di civiltà, veicolo di una lingua viva e “in situazione” ed esperienza di apprendimento plurisensoriale, l’articolo mette in luce come l’apprendimento dell’italiano L2 possa trarre beneficio dall’utilizzo in aula di materiali audiovisivi autentici quali i film, se opportunamente selezionati e didattizzati. Dalla riflessione alla pratica: dopo aver identificato obiettivi, destinatari ed i loro bisogni linguistico-comunicativi, viene presentata un’attività basata sulla didattizzazione di tre sequenze che hanno come tema centrale l’esame universitario orale. Ponendo i bisogni linguistico-comunicativi dei discenti al centro si scoprirà che, se opportunamente didattizzato, un film o parte di esso può trasformarsi in materiale didattico estremamente utile ai fini dell’apprendimento di una L2, nonché fonte inesauribile di spunti a partire dai quali l’insegnante può creare attività didattiche originali e stimolanti non solo linguistiche ma anche interculturali. Movies during italian l2 lessons: exams at the cinemaAre movies useful tools during Italian L2 lessons? What are the limits and advantages of using authentic audio-visual materials in the classroom? How can an activity based on viewing an Italian film in the original language be structured? What strategies do learners use to understand movies in

  14. Phe-Gly dipeptidomimetics designed for the di-/tripeptide transporters PEPT1 and PEPT2

    DEFF Research Database (Denmark)

    Våbenø, Jon; Lejon, Tore; Nielsen, Carsten Uhd

    2004-01-01

    A series of five Phe-Gly dipeptidomimetics containing different amide bond replacements have been synthesized in a facile way from the readily available unsaturated ketoester 1, and their affinities for the di-/tripeptide transporters hPEPT1 (Caco-2 cells) and rPEPT2 (SKPT cells) were tested...... information about the importance of flexibility and of the stereochemistry at the C(4)-position for this class of compounds. Furthermore, the intracellular uptake of 2a-4a in Caco-2 cells was investigated, showing a 3-fold reduction of the uptake of 2a in the presence of the competetive inhibitor Gly......-Pro, indicating contribution from an active transport component. No active uptake of 3a and 4a was observed. Transepithelial transport studies also indicated active transport of 2a across Caco-2 monolayers....

  15. Surface Chirality of Gly-Pro Dipeptide Adsorbed on a Cu(110) Surface.

    Science.gov (United States)

    Cruguel, Hervé; Méthivier, Christophe; Pradier, Claire-Marie; Humblot, Vincent

    2015-07-01

    The adsorption of chiral Gly-Pro dipeptide on Cu(110) has been characterized by combining in situ polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS). The chemical state of the dipeptide, and its anchoring points and adsorption geometry, were determined at various coverage values. Gly-Pro molecules are present on Cu(110) in their anionic form (NH2 /COO(-)) and adsorb under a 3-point binding via both oxygen atoms of the carboxylate group and via the nitrogen atom of the amine group. Low-energy electron diffraction (LEED) and scanning tunneling microscopy (STM) have shown the presence of an extended 2D chiral array, sustained via intermolecular H-bonds interactions. Furthermore, due to the particular shape of the molecule, only one homochiral domain is formed, creating thus a truly chiral surface. © 2015 Wiley Periodicals, Inc.

  16. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    Energy Technology Data Exchange (ETDEWEB)

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6‑thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6‑Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6‑Bcl-xL gly-159-ala clone #38 cells.

  17. Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

    Science.gov (United States)

    Antonicelli, L; Ruello, M L; Monsalve, R I; González, R; Fava, G; Bonifazi, F

    2010-10-01

    Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

  18. MicroRNAs Promote Granule Cell Expansion in the Cerebellum Through Gli2.

    Science.gov (United States)

    Constantin, Lena; Wainwright, Brandon J

    2015-12-01

    MicroRNAs (miRNAs) are important regulators of cerebellar function and homeostasis. Their deregulation results in cerebellar neuronal degeneration and spinocerebellar ataxia type 1 and contributes to medulloblastoma. Canonical miRNA processing involves Dicer, which cleaves precursor miRNAs into mature double-stranded RNA duplexes. In order to address the role of miRNAs in cerebellar granule cell precursor development, loxP-flanked exons of Dicer1 were conditionally inactivated using the granule cell precursor-specific Atoh1-Cre recombinase. A reduction of 87% in Dicer1 transcript was achieved in this conditional Dicer knockdown model. Although knockdown resulted in normal survival, mice had disruptions to the cortical layering of the anterior cerebellum, which resulted from the premature differentiation of granule cell precursors in this region during neonatal development. This defect manifested as a thinner external granular layer with ectopic mature granule cells, and a depleted internal granular layer. We found that expression of the activator components of the Hedgehog-Patched pathway, the Gli family of transcription factors, was perturbed in conditional Dicer knockdown mice. We propose that loss of Gli2 mRNA mediated the anterior-restricted defect in conditional Dicer knockdown mice and, as proof of principle, were able to show that miR-106b positively regulated Gli2 mRNA expression. These findings confirm the importance of miRNAs as positive mediators of Hedgehog-Patched signalling during granule cell precursor development.

  19. Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

    Science.gov (United States)

    Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

    2017-10-01

    Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

  20. Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1.

    Directory of Open Access Journals (Sweden)

    Frank Götschel

    Full Text Available Aberrant activation of Hedgehog (HH signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. Our experimental data demonstrated that the Daoy human medulloblastoma cell line possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic HH or Smoothened agonist induced expression of GLI1 protein and simultaneously prevented the processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed at the transcriptomic and proteomic levels. The Daoy cells responded to the HH/EGF co-treatment by downregulating GLI1, PTCH, and HHIP at the transcript level; this was also observed when Amphiregulin (AREG was used instead of EGF. We identified a novel crosstalk mechanism whereby EGFR signaling silences proteins acting as negative regulators of HH signaling, as AKT- and ERK-signaling independent process. EGFR/HH signaling maintained high GLI1 protein levels which contrasted the GLI1 downregulation on the transcript level. Conversely, a high-level synergism was also observed, due to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile. This suggests that there are more wide-spread, yet context-dependent interactions, between HH/GLI and growth factor receptor signaling in human malignancies.

  1. Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb.

    Science.gov (United States)

    Lallemand, Yvan; Bensoussan, Vardina; Cloment, Cécile Saint; Robert, Benoît

    2009-07-15

    In tetrapods, the anteroposterior (AP) patterning of the limb is under the control of the antagonistic activities of the secreted factor Sonic hedgehog (Shh) and Gli3R, the truncated repressor form of the transcription factor Gli3. In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R. Consequently, in Shh null mutants, Msx genes are overexpressed and, furthermore, partially responsible for the limb phenotype. This is exemplified by the fact that reducing Msx activity in Shh mutants partially restores a normal limb development. Finally, we show that the main action of the Msx genes, in both normal and Shh(-/-) limb development, is to control cell death in the mesenchyme. We propose that, in the limb, Msx genes act downstream of the Shh/Gli3 pathway by transducing BMP signaling and that, in the absence of Shh signaling, their deregulation contributes to the extensive apoptosis that impairs limb development.

  2. AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yen-Hsing Li

    2015-07-01

    Full Text Available The Hedgehog (Hh pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

  3. Batteri lattici non starter durante la stagionatura del formaggio: sopravvivenza, crescita e produzione di molecole potenzialmente coinvolte nella formazione dell'aroma

    OpenAIRE

    Sgarbi, Elisa

    2012-01-01

    I batteri lattici (LAB) costituiscono un gruppo eterogeneo di batteri tradizionalmente utilizzati nella produzione di formaggi. Essi possono svolgere diversi ruoli durante la caseificazione, gli starter LAB (SLAB) sono i protagonisti del processo di fermentazione, mentre i non starter LAB (NSLAB) esplicano il loro ruolo durante la maturazione del formaggio. Il lavoro di ricerca di questo dottorato si è focalizzato sullo studio del contributo dei NSLAB durante la stagionatura del formaggio. In...

  4. Lithium Suppresses Hedgehog Signaling via Promoting ITCH E3 Ligase Activity and Gli1–SUFU Interaction in PDA Cells

    Directory of Open Access Journals (Sweden)

    Xinshuo Wang

    2017-11-01

    Full Text Available Dysregulation of Hedgehog (Hh signaling pathway is one of the hallmarks of pancreatic ductal adenocarcinoma (PDA. Lithium, a clinical mood stabilizer for the treatment of mental disorders, is known to suppress tumorigenic potential of PDA cells by targeting the Hh/Gli signaling pathway. In this study, we investigated the molecular mechanism of lithium induced down-regulation of Hh/Gli1. Our data show that lithium promotes the poly-ubiquitination and proteasome-mediated degradation of Gli1 through activating E3 ligase ITCH. Additionally, lithium enhances interaction between Gli1 and SUFU via suppressing GSK3β, which phosphorylates SUFU and destabilizes the SUFU-Gli1 inhibitory complex. Our studies illustrate a novel mechanism by which lithium suppresses Hh signaling via simultaneously promoting ITCH-dependent Gli1 ubiquitination/degradation and SUFU-mediated Gli1 inhibition.

  5. I big data e gli strumenti di visualizzazione analitica: interazioni e studi induttivi per le P.A.

    Directory of Open Access Journals (Sweden)

    Giuseppe Roccasalva

    2012-12-01

    Full Text Available Il saggio presenta alcuni risultati di una collaborazione tra Politecnico di Torino e il CSI Piemonte (Società di servizi Informatizzati partecipata dalla Regione Piemonte. Sono stati selezionati e studiati diversi strumenti di visualizzazione dei dati scientifici (Gapminder, ManyEyes, Open eXplorer e Fineo al fine di individuare quello più utile per una lettura induttiva di grandi quantità di dati informativi (big data. Lo sfruttamento intelligente dei dati digitali può portare a uno sviluppo conoscitivo ma anche a un profitto, le cui soglie di sfruttamento possono essere misurate in un sistema economico. Nell’irreversibile fenomeno di crescita dei dati digitali, la disciplina del “Data Visualization” diventa cruciale per accedere e comprendere informazioni complesse. Few, guru della comunicazione visiva, scrive che “scopriamo il mondo attraverso gli occhi”; le forme di comunicazione e interpretazione tradizionali dei dati hanno puntato sulla dimensione visuale per migliorare la comprensione e hanno permesso sia agli analisti sia agli utenti la sperimentazione di nuove interazioni (“story-telling”. Come urbanisti e cittadini, ci affidiamo alla vista che gestisce molti dei sensori (70% legati alla percezione, alle mappe cognitive, agli errori e ai nuovi pensieri. L’ipotesi di fondo di questo articolo vuole generare delle riflessioni sui Big Data come strategia importante per le imprese pubbliche e private che intendono imparare a cambiare dalle informazioni digitali di cui oggi disponiamo. Attraverso l’uso di uno strumento analitico di visualizzazione dei dati informativi, si descrive un recente caso di studio in un contesto territoriale come quello dei nuovi consorzi amministrativi (Unione dei Comuni NordEst Torino. In questo esperimento torna a essere attuale la necessità di pianificare le scelte in modo sistematico anche cercando di utilizzare in modo nuovo e semplice i sistemi informativi territoriali già disponibili.

  6. Il ruolo delle infrastrutture nella costruzione e nella percezione del territorio

    Directory of Open Access Journals (Sweden)

    Roberto Busi

    2012-08-01

    Full Text Available L’opera di pianificazione del paesaggio non può che passare attraverso la pianificazione delle componenti fisiche del territorio che, oltre agli indubitabili significati ed obiettivi funzionali, sono anche gli elementi costitutivi del paesaggio perché rappresentano le componenti percepibili del territorio medesimo; cosicché la pianificazione paesistica viene ad essere ad un tempo la diretta conseguenza e l’alta motivazione di quella urbanistico-territoriale conferendole motivi, fini e valori elevati.E le infrastrutture sono, come detto, le componenti fisiche primarie dell’antropizzazione del territorio sia in quanto tali, sia in quanto fattore per eccellenza di eventi generanti componenti fisiche.

  7. Vorrei ma non posso. L'esperienza del non realizzato nella pratica artistica contemporanea. Un'intervista con Luca Trevisani

    Directory of Open Access Journals (Sweden)

    Valentina Rossi

    2014-12-01

    Full Text Available Le domande in questa intervista seguono e riprendono l’intervento di Luca Trevisani al convegno tenutosi nel novembre del 2013 presso il Museo del Novecento di Milano. Trevisani era stato invitato per “rappresentare” una nuova generazione di artisti, che, nati tra gli anni Settanta e i primi anni Ottanta si sono trovati ad operare proprio all’inizio del nuovo millennio.

  8. Environmental analysis applied to schools. Methodologies for data acquisition; Analisi ambientale iniziale per gli istituti d'istruzione. Metodologia per l'acquisizione dei dati

    Energy Technology Data Exchange (ETDEWEB)

    Andriola, L.; Ceccacci, R. [ENEA, Div. Caratterizzazione dell' Ambiente e del Territorio, Centro Ricerche Casaccia, Rome (Italy)

    2001-07-01

    The environment analysis is the basis of environmental management for organizations and it is considered as the first step in EMAS. It allows to identify, deal with the issues and have a clear knowledge on environmental performances of organizations. Schools can be included in the organizations. Nevertheless, the complexity of environmental issues and applicable regulations makes very difficult for a school, that wants to implement an environmental management system (EMAS, ISO 14001, etc.), to face this first step. So, it has been defined an instrument, that is easy but complete and coherent with reference standard, to let schools choose their process for elaborating the initial environmental revue. This instrument consists, essentially, in cards that, if completed, facilitate the drafting of the environmental analysis report. [Italian] L'analisi ambientale iniziale costituisce il presupposto di qualsiasi azione di gestione ambientale da parte di un'organizzazione ed e' esplicitamente prevista, come prima tappa, in EMAS. Essa consente infatti di individuare ed approfondire le problematiche ambientali e di fotografare, per mezzo di riferimenti oggettivi, le prestazioni ambientali di un'organizzazione, e quindi anche di una scuola, in modo da poter stabilire e controllare nel tempo gli obiettivi di miglioramento. Tuttavia la complessita' delle problematiche ambientali e delle relative normative di riferimento rende estremamente difficoltoso, per un istituto scolastico che intenda intraprendere un percorso di gestione ambientale comunque finalizzato (EMAS, ISO 14001, Comunicazione ambientale, ecc.) compiere questo passo iniziale. E' stato pertanto realizzato uno strumento semplificato, ma comunque completo e coerente con gli standard di riferimento, per consentire alle scuole di effettuare il percorso di elaborazione di un'analisi ambientale iniziale. Lo strumento consiste essenzialmente in schede che, una volta compilate

  9. Environmental analysis applied to schools. Methodologies for data acquisition; Analisi ambientale iniziale per gli istituti d'istruzione. Metodologia per l'acquisizione dei dati

    Energy Technology Data Exchange (ETDEWEB)

    Andriola, L; Ceccacci, R [ENEA, Div. Caratterizzazione dell' Ambiente e del Territorio, Centro Ricerche Casaccia, Rome (Italy)

    2001-07-01

    The environment analysis is the basis of environmental management for organizations and it is considered as the first step in EMAS. It allows to identify, deal with the issues and have a clear knowledge on environmental performances of organizations. Schools can be included in the organizations. Nevertheless, the complexity of environmental issues and applicable regulations makes very difficult for a school, that wants to implement an environmental management system (EMAS, ISO 14001, etc.), to face this first step. So, it has been defined an instrument, that is easy but complete and coherent with reference standard, to let schools choose their process for elaborating the initial environmental revue. This instrument consists, essentially, in cards that, if completed, facilitate the drafting of the environmental analysis report. [Italian] L'analisi ambientale iniziale costituisce il presupposto di qualsiasi azione di gestione ambientale da parte di un'organizzazione ed e' esplicitamente prevista, come prima tappa, in EMAS. Essa consente infatti di individuare ed approfondire le problematiche ambientali e di fotografare, per mezzo di riferimenti oggettivi, le prestazioni ambientali di un'organizzazione, e quindi anche di una scuola, in modo da poter stabilire e controllare nel tempo gli obiettivi di miglioramento. Tuttavia la complessita' delle problematiche ambientali e delle relative normative di riferimento rende estremamente difficoltoso, per un istituto scolastico che intenda intraprendere un percorso di gestione ambientale comunque finalizzato (EMAS, ISO 14001, Comunicazione ambientale, ecc.) compiere questo passo iniziale. E' stato pertanto realizzato uno strumento semplificato, ma comunque completo e coerente con gli standard di riferimento, per consentire alle scuole di effettuare il percorso di elaborazione di un'analisi ambientale iniziale. Lo strumento consiste essenzialmente in schede che, una volta compilate, faciliteranno la stesura del rapporto di

  10. Franco Modigliani e la teoria del ciclo vitale del consumo

    Directory of Open Access Journals (Sweden)

    Angus Deaton

    2005-06-01

    Full Text Available Nei primi anni ’50, Franco Modigliani e il suo studente Richard Brumberg elaborarono una teoria della spesa fondata sull’idea che gli individui effettuano scelte intelligenti su quanto desiderano spendere a ogni età, con il solo limite delle risorse disponibili nel corso della loro vita. Attraverso l’accumulo e il decumulo delle attività, chi lavora può provvedere alla propriapensione e, più in generale, può adattare i propri modelli di consumo alle esigenze che sipresentano alle diverse età, indipendentemente dal reddito disponibile in ogni momento della suavita. Questa semplice teoria conduce a previsioni rilevanti e non scontate per l’economia nel suo complesso, ad esempio che il risparmio nazionale dipende dal tasso di crescita del reddito nazionale e non dal suo livello, e che esiste una semplice relazione tra il livello della ricchezza nelsistema economico e la lunghezza del periodo trascorso in pensione. Tali previsioni, non verificabili negli anni ’50, hanno trovato considerevole sostegno empirico in successivi lavori di Modigliani e di altri ricercatori. Sebbene nel corso degli anni la teoria del consumo abbia subitonumerosi attacchi, i più recenti dei quali mossi da una coalizione di psicologi ed economisti,l’ipotesi del ciclo vitale rimane una parte essenziale del pensiero degli economisti.

  11. Esercizi scelti di algebra

    CERN Document Server

    Chirivì, Rocco; Dvornicich, Roberto

    2017-01-01

    Questo libro – primo di due volumi -  presenta oltre 250 esercizi scelti di algebra ricavati dai compiti d'esame dei corsi di Aritmetica tenuti dagli autori all'Università di Pisa. Ogni esercizio viene presentato con una o più soluzioni accuratamente redatte con linguaggio e notazioni uniformi. Caratteristica distintiva del libro è che gli esercizi proposti sono tutti diversi uno dall'altro e le soluzioni richiedono sempre una piccola idea originale; ciò rende il libro unico nel genere. Gli argomenti di questo primo volume sono: principio d'induzione, combinatoria, congruenze, gruppi abeliani, anelli commutativi, polinomi, estensioni di campi, campi finiti. Il libro contiene inoltre una dettagliata sezione di richiami teorici e può essere usato come libro di riferimento per lo studio. Una serie di esercizi preliminari introduce le tecniche principali da usare per confrontarsi con i testi d'esame proposti. Il volume è rivolto a tutti gli studenti del primo anno dei corsi di laur ea in Matematica e Inf...

  12. [Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].

    Science.gov (United States)

    Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.

  13. Structure/Function Studies of the α4 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses

    Directory of Open Access Journals (Sweden)

    Sophie Leacock

    2018-01-01

    Full Text Available Inhibitory glycine receptors (GlyRs are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1, cortical neuronal migration/autism spectrum disorder (GlyR α2, and inflammatory pain sensitization/rhythmic breathing (GlyR α3. However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene (GLRA4 is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4. Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies. Analyzing data from sequenced genomes, we found that GlyR α4 subunit genes are predicted to be intact and functional in the majority of vertebrate species—with the exception of humans. Cloning of human GlyR α4 cDNAs excluded alternative splicing and RNA editing as mechanisms for restoring a full-length GlyR α4 subunit. Moreover, artificial restoration of the missing conserved arginine (R390 in the human cDNA was not sufficient to restore GlyR α4 function. Further bioinformatic and mutagenesis analysis revealed an additional damaging substitution at K59 that ablates human GlyR α4 function, which is not present in other vertebrate GlyR α4 sequences. The substitutions K59 and X390 were also present in the genome of an ancient Denisovan individual, indicating that GLRA4 has been a pseudogene for at least 30,000–50,000 years. In artificial synapses, we found that both mouse and gorilla α4β GlyRs mediate synaptic currents with unusually slow decay kinetics. Lastly, to gain insights into the biological role of GlyR α4 function, we studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line (SAIGFF16B, we found that the zebrafish GlyR α4a subunit gene (glra4a is strongly expressed in spinal cord and hindbrain commissural

  14. Reactivity of cosmetic UV filters towards skin proteins: model studies with Boc-lysine, Boc-Gly-Phe-Gly-Lys-OH, BSA and gelatin.

    Science.gov (United States)

    Stiefel, C; Schwack, W

    2014-12-01

    Organic UV filters are used as active ingredients in most sunscreens and also in a variety of daily care products. Their good (photo) stability is of special interest to guarantee protective function and to prevent interactions with the human skin. Due to the mostly electrophilic character of the UV filters, reactions with nucleophilic protein moieties like lysine side chains are conceivable. Prior studies showed that the UV filters octocrylene (OCR), butyl methoxydibenzoylmethane (BM-DBM), ethylhexyl salicylate (EHS), ethylhexyl methoxycinnamate (EHMC), benzophenone-3 (BP-3), ethylhexyl triazone (EHT) and dibenzoylmethane (DBM) were able to covalently bind to an HPTLC amino phase and the amino acid models ethanolamine and butylamine after slightly heating and/or radiation. Boc-protected lysine, the tetrapeptide Boc-Gly-Phe-Gly-Lys-OH, bovine serum albumin (BSA) and porcine gelatin were used as more complex models to determine the reactivity of the mentioned UV filters towards skin proteins under thermal or UV irradiation conditions. After gentle heating at 37°C, benzophenone imines were identified as reaction products of BP-3 and OCR with Boc-lysine and the tetrapeptide, whereas DBM and BM-DBM yielded enamines. For EHMC, a Michael-type reaction occurred, which resulted in addition of Boc-lysine or the tetrapeptide to the conjugated double bond. Ester aminolysis of EHS and EHT mainly afforded the corresponding amides. Reactions of the UV filters with BSA changed the UV spectrum of BSA, generally associated with an increase of the absorption strength in the UVA or UVB range. For all protein models, the UV filters showed an increasing reactivity in the order EHT < EHMC < EHS < BP-3 < OCR < DBM < BM-DBM. Especially the UV absorbers BM-DBM, OCR and BP-3, which are seen as common allergens or photoallergens, showed a high reactivity towards the different skin protein models. As the formation of protein adducts is recognized as important key element in the induction of

  15. Considerazioni sul problema dei rigassificatori tra aggregazione del consenso e conflitto ambientale

    OpenAIRE

    Lodoli, Flavio

    2011-01-01

    2009/2010 Considerazioni sul problema dei Rigassificatori tra Aggregazione del Consenso e Conflitto Ambientale 1. Il nostro Paese, per scelta politica e per una sostanziale limitata capacità di innovazione del mondo industriale, ha una quota attuale di produzione di energia da fonti rinnovabili poco significativa nonostante gli investimenti, i contributi e le agevolazioni fiscali che dovrebbero incentivare opportunamente ad esempio, l’utilizzo dell’energia solare che rappresenta una...

  16. Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

    Energy Technology Data Exchange (ETDEWEB)

    Lesoil, Charles [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Nonaka, Takahiro [Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585 (Japan); Sekiguchi, Hiroshi; Osada, Toshiya [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Miyata, Makoto [Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585 (Japan); Afrin, Rehana [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Biofrontier Center, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Ikai, Atsushi, E-mail: ikai.a.aa@m.titech.ac.jp [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan)

    2010-01-15

    Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

  17. Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

    International Nuclear Information System (INIS)

    Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

    2010-01-01

    Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

  18. GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor

    International Nuclear Information System (INIS)

    Chen, Guangchun; Goto, Yutaka; Sakamoto, Ryuichi; Tanaka, Kimitaka; Matsubara, Eri; Nakamura, Masafumi; Zheng, Hong; Lu, Jian; Takayanagi, Ryoichi; Nomura, Masatoshi

    2011-01-01

    Research highlights: → GLI1, which play a central role in sonic hedgehog signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor-mediated transactivation. → GLI1 directly interacts with AR. → SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state. -- Abstract: Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

  19. Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

    Directory of Open Access Journals (Sweden)

    Kyu Sang Joeng

    Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

  20. Molecular Determinants for Substrate Interactions with the Glycine Transporter GlyT2.

    Science.gov (United States)

    Carland, Jane E; Thomas, Michael; Mostyn, Shannon N; Subramanian, Nandhitha; O'Mara, Megan L; Ryan, Renae M; Vandenberg, Robert J

    2018-03-21

    Transporters in the SLC6 family play key roles in regulating neurotransmission and are the targets for a wide range of therapeutics. Important insights into the transport mechanisms and the specificity of drug interactions of SLC6 transporters have been obtained from the crystal structures of a bacterial homologue of the family, LeuT Aa , and more recently the Drosophila dopamine transporter and the human serotonin transporter. However, there is disputed evidence that the bacterial leucine transporter, LeuT Aa , contains two substrate binding sites that work cooperatively in the mechanism of transport, with the binding of a second substrate being required for the release of the substrate from the primary site. An alternate proposal is that there may be low affinity binding sites that serve to direct the flow of substrates to the primary site. We have used a combination of molecular dynamics simulations of substrate interactions with a homology model of GlyT2, together with radiolabeled amino acid uptake assays and electrophysiological analysis of wild-type and mutant transporters, to provide evidence that substrate selectivity of GlyT2 is determined entirely by the primary substrate binding site and, furthermore, if a secondary site exists then it is a low affinity nonselective amino acid binding site.

  1. Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein.

    Science.gov (United States)

    Allen, R C; Russell, S R; Streb, L M; Alsheikheh, A; Stone, E M

    2006-02-01

    To determine the molecular pathology and clinical severity of two pedigrees with a history of early retinal detachment and peripheral retinal vascular abnormalities. Longitudinal cohort study. A longitudinal clinical study and DNA analysis was performed on 49 family members of two pedigrees. Nine individuals were found to be hemizygous for a mutation at codon 112 (Gly112Glu) of the Norrie disease protein (NDP) in one pedigree. Significant phenotypic heterogeneity was found. The proband presented with a unilateral subtotal retinal detachment at the age of 3 years, and subsequently developed a slowly progressive tractional retinal detachment involving the macula in the contralateral eye at the age of 4 years. One individual had only mild peripheral retinal pigmentary changes with normal vision at the age of 79 years. The remaining seven individuals had varying degrees of peripheral retinal vascular abnormalities and anterior segment findings. Seven affected members of a second pedigree affected by a previously reported mutation, Arg74Cys, also demonstrated wide ocular phenotypic variation. A novel mutation (Gly112Glu), which represents the most carboxy located, NDP mutation reported, results in significant phenotypic heterogeneity. These data support the contention that the spectrum of ocular disease severity associated with these NDP mutations is broad. Use of terms that characterize this entity by phenotypic appearance, such as familial exudative vitreoretinopathy, do not adequately communicate the potential spectrum of severity of this disorder to affected or carrier family members.

  2. Loss-of-Function of Gli3 in Mice Causes Abnormal Frontal Bone Morphology and Premature Synostosis of the Interfrontal Suture

    OpenAIRE

    Veistinen, Lotta; Takatalo, Maarit; Tanimoto, Yukiho; Kesper, Dörthe A.; Vortkamp, Andrea; Rice, David P. C.

    2012-01-01

    Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder with polydactyly and syndactyly of the limbs and a broad spectrum of craniofacial abnormalities. Craniosynostosis of the metopic suture (interfrontal suture in mice) is an important but rare feature associated with GCPS. GCPS is caused by mutations in the transcription factor GLI3, which regulates Hedgehog signaling. The Gli3 loss-of-function (Gli3Xt-J/Xt-J) mouse largely phenocopies the human syndrome with the mice...

  3. Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

    Science.gov (United States)

    Hu, Yi; Ma, Lifu; Wu, Min; Wong, Melissa S; Li, Bei; Corral, Sergio; Yu, Zhizhou; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R; Rosenblum, Jonathan S; Rozenkrants, Natasha; Minimo, Lauro C; Ripka, William C; Szardenings, Anna K; Kozarich, John W; Shreder, Kevin R

    2005-10-01

    The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

  4. Funzioni del tempo presente nella strategia narrativa

    Directory of Open Access Journals (Sweden)

    Aleksandra Koman

    2017-08-01

    Full Text Available La scelta del tempo verbale adatto a una determinata situazione dipende dal rapporto tra il momento dell’avvenimento e quello dell’enunciazione. Se coincidono abbiamo a che fare con il tempo presente (Bertinetto. È necessario, però, ricordare che il presente è in grado di riferirsi agli eventi passati come accade spesso nei testi narrativi. Per capire lo scopo di questa scelta si sono analizzati diversi tipi di scrittura comprovanti che il presente nella narrativa può servire a sottolineare la posizione temporale del narratore (Il fu Mattia Pascal; a evidenziare un momento importante dal punto di vista dello svolgimento dell’azione (Se questo è un uomo; a costruire descrizioni (Vita oppure far entrare il lettore nel vivo del racconto (Gli Italiani in Polonia nei secoli, dando l’impressione che egli sia un testimone diretto degli eventi raccontati.

  5. Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties.

    Science.gov (United States)

    Santora, Vincent J; Almos, Theresa A; Barido, Richard; Basinger, Jillian; Bellows, Chris L; Bookser, Brett Carder; Breitenbucher, J Guy; Broadbent, Nicola J; Cabebe, Clifford; Chai, Chih-Kun; Chen, Mi; Chow, Stephine; Chung, De Michael; Crickard, Lindsay; Danks, Anne M; Freestone, Graeme; Gitnick, Dany; Gupta, Varsha; Hoffmaster, Christine; Hudson, Andrew R; Kaplan, Alan P; Kennedy, Michael R; Lee, Dong; Limberis, James; Ly, Kiev; Mak, Chi Ching; Masatsugu, Brittany; Morse, Andrew C; Na, Jim; Neul, David; Nikpur, John; Peters, Marco; Petroski, Robert E; Renick, Joel; Sebring, Kristen; Sevidal, Samantha; Tabatabaei, Ali; Wen, Jenny; Yan, Yingzhuo; Yoder, Zachary W; Zook, Douglas

    2018-06-11

    We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4-c]pyrazoles amides (21-50) with good in vitro potency. Subsequent optimization of physicochemical and in vitro ADME properties produced several compounds with promising pharmacokinetic profiles. In vivo inhibition of GlyT1 was demonstrated for select compounds within this series by measuring the elevation of glycine in the cerebrospinal fluid (CSF) of rats after a single oral dosing of 10 mg/kg. Ultimately, an optimized lead, compound 46, demonstrated in vivo efficacy in a rat Novel Object Recognition (NOR) assay after oral dosing at 0.1, 1, and 3 mg/kg.

  6. The Role of the PGC1α Gly482Ser Polymorphism in Weight Gain due to Intensive Diabetes Therapy

    Directory of Open Access Journals (Sweden)

    Samir S. Deeb

    2009-01-01

    Full Text Available The Diabetes Control and Complications Trial (DCCT involved intensive diabetes therapy of subjects with type 1 diabetes mellitus (T1DM for an average period of 6.5 years. A subset of these subjects gained excessive weight. We tested for association of polymorphisms in 8 candidate genes with the above trait. We found the Gly482Ser polymorphism in the peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α to be significantly associated with weight gain in males (P=.0045 but not in females. The Ser allele was associated with greater weight gain than the Gly allele (P=.005. Subjects with a family history of type 2 diabetes mellitus (T2DM were more common among those who gained excessive weight. We conclude that T2DM and the Gly482Ser polymorphism in PGC1α contribute to the effect of intensive diabetes therapy on weight gain in males with T1DM.

  7. Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements.

    Science.gov (United States)

    Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

    2015-04-21

    Limb skeletal elements originate from the limb progenitor cells, which undergo expansion and patterning to develop each skeletal element. Posterior-distal skeletal elements, such as the ulna/fibula and posterior digits develop in a Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how anterior-proximal elements, such as the humerus/femur, the radius/tibia and the anterior digits, are developed. Here we show that the zinc finger factors Sall4 and Gli3 cooperate for proper development of the anterior-proximal skeletal elements and also function upstream of Shh-dependent posterior skeletal element development. Conditional inactivation of Sall4 in the mesoderm before limb outgrowth caused severe defects in the anterior-proximal skeletal elements in the hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but not in forelimbs. This reduction caused posteriorization of nascent hindlimb buds, which is correlated with a loss of anterior digits. In proximal development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to proliferative expansion of cells in the mesenchymal core of nascent hindlimb buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic analysis identified that the Sall4-Gli3 system is a common regulator of the early limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore- and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3 system at the early steps of limb development for proper development of the appendicular skeletal elements.

  8. Antithrombotic Protective Effects of Arg-Pro-Gly-Pro Peptide during Emotional Stress Provoked by Forced Swimming Test in Rats.

    Science.gov (United States)

    Grigor'eva, M E; Lyapina, L A

    2017-01-01

    Blood coagulation was enhanced and all factors (total, enzyme, and non-enzyme) of the fibrinolytic system were suppressed in rats in 60 min after forced swimming test. Argininecontaining tetrapeptide glyproline Arg-Pro-Gly-Pro administered prior to this test activated fibrinolysis and prevented hypercoagulation. Administration of this peptide in 5 min after swimming test also enhanced anticoagulant, fibrinolytic, and antithrombotic activity of the blood. Therefore, glyproline Arg-Pro-Gly-Pro exerted both preventive and curative effects on the hemostasis system and prevented enhancement of blood coagulation provoked by emotional stress modeled by forced swimming test.

  9. Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

    Science.gov (United States)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Myoung Hyoun; Kim, Dae-Weung; Park, Cho Rong; Park, Ji Yong; Lee, Yun-Sang; Youn, Hyewon; Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key

    2016-06-01

    The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE. The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re

  10. Ebdomadari versus canonici: gli istituti clericali, il potere ecclesiale e la topografia medievale del complesso episcopale di Napoli

    Directory of Open Access Journals (Sweden)

    Lucherini, Vinni

    2006-12-01

    Full Text Available

    This article suggests a new interpretation of a series of medieval records (X-XIV centuries, in which the congregatio ecclesiae Sanctae Restitutae and the congregatio Salvatoris, are mentioned, both congregations of priests attached to Naples Cathedral. The authoress reaches the conclusion that these were not two chapters of canons corresponding to two different cathedral buildings: Santa Restituta and the Salvatore, but rather two hierarchically different congregations within the same Cathedral. The members on one of these congregations -from 1337 officially called Ebdomadari-, in the 18th century, invented the tradition of a second old Cathedral, for economic reasons and to increase their power.



    In questo articolo si propone una nuova interpretazione di una serie di documenti medievali (X-XIV secolo menzionanti le congregazioni clericali della Chiesa cattedrale napoletana, la congregatio ecclesiae Sanctae Restitutae e la congregatio Salvatoris. Le conclusioni a cui si giunge è che non si tratta di due Capitoli di Canonici facenti capo a due distinti edifici cattedrali, Santa Restituta e il Salvatore, ma di due congregazioni gerarchicamente differenziate all’interno della medesima Cattedrale, i membri di una delle quali, ufficialmente chiamati dal 1337 Ebdomadari, inventarono nel Settecento, per ragioni di denaro e di potere, la tradizione di un seconda antica Cattedrale.

  11. Constitutive endocytosis and turnover of the neuronal glycine transporter GlyT2 is dependent on ubiquitination of a C-terminal lysine cluster.

    Directory of Open Access Journals (Sweden)

    Jaime de Juan-Sanz

    Full Text Available Inhibitory glycinergic neurotransmission is terminated by sodium and chloride-dependent plasma membrane glycine transporters (GlyTs. The mainly glial glycine transporter GlyT1 is primarily responsible for the completion of inhibitory neurotransmission and the neuronal glycine transporter GlyT2 mediates the reuptake of the neurotransmitter that is used to refill synaptic vesicles in the terminal, a fundamental role in the physiology and pathology of glycinergic neurotransmission. Indeed, inhibitory glycinergic neurotransmission is modulated by the exocytosis and endocytosis of GlyT2. We previously reported that constitutive and Protein Kinase C (PKC-regulated endocytosis of GlyT2 is mediated by clathrin and that PKC accelerates GlyT2 endocytosis by increasing its ubiquitination. However, the role of ubiquitination in the constitutive endocytosis and turnover of this protein remains unexplored. Here, we show that ubiquitination of a C-terminus four lysine cluster of GlyT2 is required for constitutive endocytosis, sorting into the slow recycling pathway and turnover of the transporter. Ubiquitination negatively modulates the turnover of GlyT2, such that increased ubiquitination driven by PKC activation accelerates transporter degradation rate shortening its half-life while decreased ubiquitination increases transporter stability. Finally, ubiquitination of GlyT2 in neurons is highly responsive to the free pool of ubiquitin, suggesting that the deubiquitinating enzyme (DUB ubiquitin C-terminal hydrolase-L1 (UCHL1, as the major regulator of neuronal ubiquitin homeostasis, indirectly modulates the turnover of GlyT2. Our results contribute to the elucidation of the mechanisms underlying the dynamic trafficking of this important neuronal protein which has pathological relevance since mutations in the GlyT2 gene (SLC6A5 are the second most common cause of human hyperekplexia.

  12. Genetic variations and alternative splicing. The Glioma associated oncogene 1, GLI1.

    Directory of Open Access Journals (Sweden)

    Peter eZaphiropoulos

    2012-07-01

    Full Text Available Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation.

  13. TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis.

    Science.gov (United States)

    Sellers, R M; Payne, J B; Yu, F; LeVan, T D; Walker, C; Mikuls, T R

    2016-04-01

    Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar bone height loss (ABHL) and periodontitis, accounting for interactions between this SNP with smoking and P. gingivalis prevalence. The CD14/-260 SNP (rs2569190) served as a control, as a recent meta-analysis suggested no relationship between this SNP and periodontitis. This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case-control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full-mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL was measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected a priori and genotypes were determined using the ImmunoChip array (Illumina(®) ). Minor allele frequencies and associations with periodontitis and ABHL did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P. gingivalis was detected in subgingival plaque by PCR. Multivariate ordinal

  14. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: Robust phenotype prediction from the type and position of GLI3 mutations

    NARCIS (Netherlands)

    Johnston, Jennifer J.; Olivos-Glander, Isabelle; Killoran, Christina; Elson, Emma; Turner, Joyce T.; Peters, Kathryn F.; Abbott, Margaret H.; Aughton, David J.; Aylsworth, Arthur S.; Bamshad, Michael J.; Booth, Carol; Curry, Cynthia J.; David, Albert; Dinulos, Mary Beth; Flannery, David B.; Fox, Michelle A.; Graham, John M.; Grange, Dorothy K.; Guttmacher, Alan E.; Hannibal, Mark C.; Henn, Wolfram; Hennekam, Raoul C. M.; Holmes, Lewis B.; Hoyme, H. Eugene; Leppig, Kathleen A.; Lin, Angela E.; Macleod, Patrick; Manchester, David K.; Marcelis, Carlo; Mazzanti, Laura; McCann, Emma; McDonald, Marie T.; Mendelsohn, Nancy J.; Moeschler, John B.; Moghaddam, Billur; Neri, Giovanni; Newbury-Ecob, Ruth; Pagon, Roberta A.; Phillips, John A.; Sadler, Laurie S.; Stoler, Joan M.; Tilstra, David; Walsh Vockley, Catherine M.; Zackai, Elaine H.; Zadeh, Touran M.; Brueton, Louise; Black, Graeme Charles M.; Biesecker, Leslie G.

    2005-01-01

    Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and

  15. The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

    2012-01-01

    A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype...

  16. A Patient With a Mild Holoprosencephaly Spectrum Phenotype and Heterotaxy and a 1.3 Mb Deletion Encompassing GLI2

    NARCIS (Netherlands)

    Kevelam, S.H.G.; van Harssel, J.J.; van der Zwaag, B.; Smeets, H.J.; Paulussen, A.D.; Lichtenbelt, K.D.

    2012-01-01

    Loss-of-function mutations of GLI2 are associated with features at the mild end of the holoprosencephaly spectrum, including abnormal pituitary gland formation and/or function, and craniofacial abnormalities. In addition patients may have branchial arch anomalies and polydactyly. Large,

  17. Interaction between the Gly460Trp alpha-adducin gene variant and diuretics on the risk of myocardial infarction

    NARCIS (Netherlands)

    van Wieren-de Wijer, Diane B M A; Maitland-van der Zee, Anke-Hilse; de Boer, Anthonius; Kroon, Abraham A; de Leeuw, Peter W; Schiffers, Paul; Janssen, Rob G J H; Psaty, Bruce M; van Duijn, Cornelia M; Stricker, Bruno H Ch; Klungel, Olaf H

    INTRODUCTION: The Gly460Trp variant of the alpha-adducin gene has been associated with the salt-sensitive and diuretic responsive form of hypertension. OBJECTIVE: The aim of the study was to determine whether the alpha-adducin 460Trp variant allele modifies the risk-lowering effect of diuretics on

  18. Affinity capillary electrophoresis and quantum mechanical calculations applied to investigation of [Gly(6)]-antamanide binding with sodium and potassium ions

    Czech Academy of Sciences Publication Activity Database

    Pangavhane, Sachin; Böhm, S.; Makrlík, E.; Ruzza, P.; Kašička, Václav

    2017-01-01

    Roč. 38, č. 12 (2017), s. 1551-1559 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA15-01948S Institutional support: RVO:61388963 Keywords : affinity capillary electrophoresis * density functional theory * [Gly(6)]-antamanide * peptide complex * stability constant Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.744, year: 2016

  19. Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Kotani Hidehito

    2009-07-01

    Full Text Available Abstract Background The Hedgehog (HH pathway promotes tumorigenesis in a diversity of cancers. Activation of the HH signaling pathway is caused by overexpression of HH ligands or mutations in the components of the HH/GLI1 cascade, which lead to increased transactivation of GLI transcription factors. Although negative kinase regulators that antagonize the activity of GLI transcription factors have been reported, including GSK3β, PKA and CK1s, little is known regarding positive kinase regulators that are suitable for use on cancer therapeutic targets. The present study attempted to identify kinases whose silencing inhibits HH/GLI signalling in non-small cell lung cancer (NSCLC. Results To find positive kinase regulators in the HH pathway, kinome-wide siRNA screening was performed in a NSCLC cell line, A549, harboring the GLI regulatory reporter gene. This showed that p70S6K2-silencing remarkably reduced GLI reporter gene activity. The decrease in the activity of the HH pathway caused by p70S6K2-inhibition was accompanied by significant reduction in cell viability. We next investigated the mechanism for p70S6K2-mediated inhibition of GLI1 transcription by hypothesizing that GSK3β, a negative regulator of the HH pathway, is activated upon p70S6K2-silencing. We found that phosphorylated-GSK3β (Ser9 was reduced by p70S6K2-silencing, causing a decreased level of GLI1 protein. Finally, to further confirm the involvement of p70S6K2 in GLI1 signaling, down-regulation in GLI-mediated transcription by PI3KCA-inhibition was confirmed, establishing the pivotal role of the PI3K/p70S6K2 pathway in GLI1 cascade regulation. Conclusion We report herein that inhibition of p70S6K2, known as a downstream effector of the PI3K pathway, remarkably decreases GLI-mediated transactivation in NSCLC by reducing phosphorylated-GSK3β followed by GLI1 degradation. These results infer that p70S6K2 is a potential therapeutic target for NSCLC with hyperactivated HH/GLI pathway.

  20. Peces del Noroeste del Ecuador

    OpenAIRE

    Barriga, Ramiro

    1994-01-01

    La ictiofauna del occidente del Ecuador es poco conocida. Los peces del noroccidente son diferentes a los del suroccidente del Ecuador. 34 familias y 82 especies fueron colectadas que equivale al 11 % de las especies de peces continentales registradas en el Ecuador. Icteogeográficamente se sabe que la costa ecuatoriana posee dos provincias: la del Pacifico Norte y la del Guayas, se determinó que el límite de las dos provincias es el río Santiago ya que las especies del mencionado río so...

  1. A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant.

    Science.gov (United States)

    Cappabianca, Maria Pia; Colosimo, Alessia; Sabatucci, Annalaura; Dainese, Enrico; Di Biagio, Paola; Piscitelli, Roberta; Sarra, Ofelia; Zei, Daniela; Amato, Antonio

    2017-01-01

    We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (-CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα anti 3.7 triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ∼40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα anti 3.7 triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82 G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β + -thalassemia (β + -thal) phenotype.

  2. Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness.

    Science.gov (United States)

    Casas, Bárbara S; Adolphe, Christelle; Lois, Pablo; Navarrete, Nelson; Solís, Natalia; Bustamante, Eva; Gac, Patricio; Cabané, Patricio; Gallegos, Ivan; Wainwright, Brandon J; Palma, Verónica

    2017-10-13

    Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC. We describe the mRNA and protein expression profile of NEO1 and its ligands (Netrin-1 and RGMA) in human and mouse control epidermis and in a broad range of human BCCs. We identify in human BCC a significant positive correlation in the levels of NEO1 receptor, NTN-1 and RGMA ligands with respect to GLI1 , the main target gene of the canonical SHH pathway. Moreover, we show via cyclopamine inhibition of the SHH/GLI pathway of ex vivo cultures that NEO1 likely functions as a downstream target of SHH/GLI signaling in the skin. We also show how Neo1 expression decreases throughout BCC progression in the K14-Cre:Ptch1 lox/lox mouse model and that aggressive subtypes of human BCC exhibit lower levels of NEO1 than non-aggressive BCC samples. Taken together, these data suggest that NEO1 is a SHH/GLI target in epidermis. We propose that NEO1 may be important in tumor onset and is then down-regulated in advanced BCC or aggressive subtypes.

  3. Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae.

    Science.gov (United States)

    De Benedetti, Stefania; Bühl, Henrike; Gaballah, Ahmed; Klöckner, Anna; Otten, Christian; Schneider, Tanja; Sahl, Hans-Georg; Henrichfreise, Beate

    2014-01-01

    For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly. D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L-alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.

  4. Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae

    Directory of Open Access Journals (Sweden)

    Stefania eDe Benedetti

    2014-02-01

    Full Text Available For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly.D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L- alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.

  5. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  6. Investigation of possible association between Ser9Gly polymorphism of the D3 dopaminergic receptor gene and response to typical antipsychotics in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Quirino Cordeiro

    Full Text Available Typical antipsychotics have a high affinity for dopamine receptors. It is therefore of interest to investigate such loci in pharmacogenetic studies on psychosis. We investigated the hypothesis that Ser9Gly polymorphism of the DRD3 gene may play a role in the differences in individual response to typical antipsychotics between schizophrenic patients. The sample was composed of 53 good responders and 59 poor ones. No significant differences between the good and poor responders were found in the allelic distribution (good responders: Ser9 61.32%, Gly9 38.67%; poor responders: Ser9 64.40%, Gly9 35.59%; odds ratio, OR = 0.88, 0.49 < OR < 1.56; chi2 = 0.23, 1 degree of freedom, df, p = 0.63 and genotype distribution (good responders: Ser9/Ser9 37.73%, Ser9/Gly9 47.16%, Gly9/Gly9 15.09%; poor responders: Ser9/Ser9 42.37%, Ser9/Gly9 44.06%, Gly9/Gly9 13.55%; chi2 = 0.25, 2 df, p = 0.88. Nor was there any association with homozygosity (good responders: homozygous: 52.82%, heterozygous: 47.16%; poor responders: homozygous: 55.92%, heterozygous: 44.06%; odds ratio, OR = 0.88, 0.39 < OR < 1.99; chi2 = 0.11, 1 df, p = 0.74. The results did not support the hypothesis that Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics in our sample of schizophrenics.

  7. La Comunità Energetica del Sud Est Europa quale fattore di stabilità nell’area Balcanica

    OpenAIRE

    Massari, Saverio Francesco

    2012-01-01

    Il lavoro cerca di valutare il possibile ruolo della Comunità Energetica del Sud Est Europa quale fattore di stabilita’ nell’area Balcanica. Il Trattato fondativo della Comunita’ assegna a questa l’obiettivo di condurre una cooperazione in campo energetico al fine diffondere istituzioni e normative condivise, quali elementi di superamento del conflitto: tuttavia, sono molti gli ostacoli posti su questo cammino sia di natura interna alla regione che esterna, per l’influenza di fattori e poter...

  8. Il progetto Waterfront: la riqualificazione del porto di Napoli

    Directory of Open Access Journals (Sweden)

    Robert Leonardi

    2009-11-01

    Full Text Available Nell'ultimo decennio Napoli ha riacquisito piena coscienza del valore della risorsa mare e le sue istituzioni ai vari livelli comunale, regionale, provinciale e dell'Autorità Portuale si sono attivate in un processo coordinato di interventi che, utilizzando gli strumenti urbanistici a tutela dell'integrità degli interventi stessi e con la partecipazione di progettisti di fama e di investitori privati, si propone di riagganciare la città al mare e di trovare nuove opportunità di crescita economica e di riscatto sociale. L’articolo descrive l’insieme di interventi che si stanno portando avanti per l’area portuale di Napoli, con particolare riferimento al progetto Waterfront, alla costituzione della società Nausicaa e al concorso internazionale per il porto di Napoli. Si specificano quindi gli attori del processo decisionale, le fasi, i contenuti delle scelte e si propone un’analisi delle ricadute d'impatto sulla città che gli interventi avranno a regime: rinnovamento civile, crescita funzionale, ricomposizione spaziale, leadership e capacità programmatica.

  9. La liberazione del tempo

    CERN Document Server

    Selleri, Franco

    2003-01-01

    Negli ultimi dieci anni ho lavorato alla descrizione dei fenomeni naturali da parte di osservatori in movimento. E' un problema che molti credono risolto una volta per tutte dalle trasformazioni di Lorentz della teoria della relatività speciale (TRS nel seguito), ma che in realtà era rimasto aperto per una serie di ragioni che esporrò. Sento di dover dire che ho trovato risultati molto importanti, anche se il giudizio finale sul loro valore non può certo essere il mio. Infatti la conclusione di questa ricerca è duplice: una spiegazione dei dati empirici migliore di quella relativistica, e l'eliminazione di quegli aspetti della TRS che fanno a pugni con il buon senso; il tutto grazie alla liberazione del tempo dall'asservimento alle coordinate spaziali cui era stato costretto nello spazio a quattro dimensioni di Minkowski. La faccenda è raccontata con dovizia di particolari in un libro recente [FS]. Nel presente articolo espongo gli aspetti salienti della ricerca lasciando da parte quelli matematici.

  10. The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy

    Science.gov (United States)

    Armas-López, Leonel; Zúñiga, Joaquín; Arrieta, Oscar; Ávila-Moreno, Federico

    2017-01-01

    Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In lung cancer, several transcriptional, epigenetic and genetic aberrations have been described to partly arise from environmental risk factors, but ethnic genetic predisposition factors may also play a role. The classification of the molecular hallmarks of cancer has been essential to study and achieve a comprehensive view of the interaction networks between cell signaling pathways and functional roles of the transcriptional and epigenetic regulatory mechanisms. This has in turn increased understanding on how these molecular networks are involved in embryo-layers and malignant diseases development. Ultimately, a major biomedicine goal is to achieve a thorough understanding of their roles as diagnostic, prognostic and treatment response indicators in lung oncological patients. Recently, several notable cell-signaling pathways have been studied based on their contribution to promoting and/or regulating the engagement of different cancer hallmarks, among them genome instability, exacerbated proliferative signaling, replicative immortality, tumor invasion-metastasis, inflammation, and immune-surveillance evasion mechanisms. Of these, the Hedgehog-GLI (Hh) cell-signaling pathway has been identified as a main molecular contribution into several of the abovementioned functional embryo-malignancy processes. Nonetheless, the systematic study of the regulatory epigenetic and

  11. La strana storia della luce e del colore

    CERN Document Server

    Guzzi, Rodolfo

    2011-01-01

    Sino al 1600 la luce era oggetto di studio degli scienziati ed il colore dei filosofi. Questa dicotomia fu superata dall’Esperimentum Crucis di Newton che spiego’ come la luce contenesse il colore. Il libro analizza le teorie che furono sviluppate dai greci, per evolversi successivamente nelle teorie degli scienziati arabi e approdare al medio evo. Con l’Esperimentum Crucis Newton dimostro’ che la luce conteneva i colori primari. Tra gli esperimenti che egli fece ci furono anche quelli sulla percezione che risultarono sbagliati; solo Goethe capi’ quale era la vera portata di quegli esperimenti e li rifece dando una interpretazione che, oggi, sappiamo essere vera, ma che a quel tempo fu alquanto osteggiata. Nel frattempo la comunita’ scientifica progrediva sul concetto di visione e di sensazione, poiche’ gli strumenti di indagine si raffinavano. Bisogna pero’ arrivare ai giorni nostri per avere una spiegazione sul comportamento della luce e del colore e come questa viene percepita da noi. Solo ...

  12. Fisica del nucleo stelle di neutroni

    CERN Document Server

    Bernardini, Carlo

    1982-01-01

    Studio sistematico delle masse nucleari ; energia di legame ; raggi nucleari dai nuclei speculari ; il nucleo in approssimazione di Thomas-Fermi ; introduzione allo scattering : caratterizzazione cinematica degli urti ; la sezione d'urto ; il fattore di forma dei nuclei ; gli atomi u-mesici ; proprieta elettromagnetiche statiche dei nuclei (momenti di multipolo) ; momento di quadrupolo elettrico dei nuclei ; momento d dipolo magnetico dei nuclei ; metodo delle risonanze magnetiche nucleari (NMR) ; misura del fattore giromagnetico e del momento di quadrupolo ; modelli nucleari a particelle indipendenti, il modello a shell ; l'interazione spin-orbita ; il modello a shell e le linee di Schmidt per il momento magnetico dei nuclei con "A" dispari ; nuclei non sferici (deformati) ; stelle di neutroni.

  13. Uno scenario da film: la "Mostra del Lazio" di Armando Brasini

    Directory of Open Access Journals (Sweden)

    Roscini Vitali, Aurora

    2015-10-01

    Full Text Available La Mostra dell’agricoltura, dell’industria e delle arti applicate, detta più comunemente “del Lazio”, tenutasi nel 1923 presso il Galoppatoio di Villa Borghese a Roma, impegnò l’architetto Armando Brasini nella realizzazione di una vera e propria “cittadella” espositiva; gli scenografici padiglioni, poi impiegati per le ambientazioni del film Quo Vadis, furono progettati come elementi cardine di un utopico spazio urbano dove potesse di-mostrarsi la rinascita, tutta fascista, del mito imperiale.

  14. New zinc-glycine-iodide complexes as a product of equilibrium and non-equilibrium crystallization in the Gly – ZnI2 – H2O system

    Czech Academy of Sciences Publication Activity Database

    Tepavitcharova, S.; Havlíček, D.; Matulková, I.; Rabadjieva, D.; Gergulova, R.; Plocek, Jiří; Němec, I.; Císařová, I.

    2016-01-01

    Roč. 1120, SEP (2016), s. 42-49 ISSN 0022-2860 Institutional support: RVO:61388980 Keywords : [Zn(gly)I2], [Zn(gly)2I2] * [Zn3(H2O)4(μ-gly)2I6] * Crystal structure * Vibrational spectra * Thermal behaviour Subject RIV: CA - Inorganic Chemistry Impact factor: 1.753, year: 2016

  15. Anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH reduces dispersion of action potential duration during ischemia/reperfusion in rabbit hearts

    DEFF Research Database (Denmark)

    Kjølbye, Anne Louise; Petersen, Jørgen Søberg; Holstein-Rathlou, N.-H.

    2002-01-01

    During ischemia, cardiac gap junctions close and neighboring cells uncouple. This leads to slow conduction, increased dispersion of APD90 (duration from action potential beginning to 90% of repolarization), nonuniform anisotropy, and unidirectional conduction block, all of which favor the induction...... of reentry arrhythmias. It has been suggested that anti-arrhythmic peptides increase gap junction conductance during states of reduced coupling. The aim of this study was to test the effect of the anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH (HP-5) (10(-10) ) on dispersion...... of epicardial APD90 during both normokalemic and hypokalemic ischemia/reperfusion in isolated perfused rabbit hearts. HP-5 did not affect average APD90, heart rate, left ventricular contractility (LVP dP/dtmax), or mean coronary flow. HP-5 significantly reduced the epicardial APD dispersion during hypokalemic...

  16. Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human Gli36 cells.

    Science.gov (United States)

    Alaimo, Agustina; Gorojod, Roxana M; Miglietta, Esteban A; Villarreal, Alejandro; Ramos, Alberto J; Kotler, Mónica L

    2013-10-25

    Manganese (Mn) is an essential trace element due to its participation in many physiological processes. However, overexposure to this metal leads to a neurological disorder known as Manganism whose clinical manifestations and molecular mechanisms resemble Parkinson's disease. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity being the mitochondria the most affected organelles. The aim of this study was to investigate the possible mitochondrial dynamics alterations in Mn-exposed human astrocytes. Therefore, we employed Gli36 cells which express the astrocytic markers GFAP and S100B. We demonstrated that Mn triggers the mitochondrial apoptotic pathway revealed by increased Bax/Bcl-2 ratio, by the loss of mitochondrial membrane potential and by caspase-9 activation. This apoptotic program may be in turn responsible of caspase-3/7 activation, PARP-1 cleavage, chromatin condensation and fragmentation. In addition, we determined that Mn induces deregulation in mitochondria-shaping proteins (Opa-1, Mfn-2 and Drp-1) expression levels in parallel with the disruption of the mitochondrial network toward to an exacerbated fragmentation. Since mitochondrial dynamics is altered in several neurodegenerative diseases, these proteins could become future targets to be considered in Manganism treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Interaction of the univalent silver cation with [Gly6]-antamanide: Experimental and theoretical study

    Science.gov (United States)

    Makrlík, Emanuel; Böhm, Stanislav; Kvíčala, Jaroslav; Vaňura, Petr; Ruzza, Paolo

    2018-03-01

    On the basis of extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Ag+(aq) + 1.Na+(nb) ⇄ 1.Ag+ (nb) + Na+(aq) occurring in the two-phase water - nitrobenzene system (1 = [Gly6]-antamanide; aq = aqueous phase, nb = nitrobenzene phase) was determined as log Kex (Ag+,1·Na+) = 1.5 ± 0.1. Further, the stability constant of the 1·Ag+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log βnb (1·Ag+) = 4.5 ± 0.2. Finally, by using quantum chemical DFT calculations, the most probable structure of the cationic complex species 1·Ag+ was derived. In the resulting complex, the "central" cation Ag+ is coordinated by four noncovalent interactions to the corresponding four carbonyl oxygen atoms of the parent ligand 1. Besides, the whole 1·Ag+ complex structure is stabilized by two intramolecular hydrogen bonds. The interaction energy of the considered 1·Ag+ complex was found to be -465.5 kJ/mol, confirming also the formation of this cationic species.

  18. Arg16Gly and Gln27Glu β2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians

    Science.gov (United States)

    Atala, Magda M; Goulart, Alessandra; Guerra, Grazia M; Mostarda, Cristiano; Rodrigues, Bruno; Mello, Priscila R; Casarine, Dulce E; Irigoyen, Maria-Claudia; Pereira, Alexandre C; Consolim-Colombo, Fernanda M

    2015-01-01

    The association between functional β2 adrenergic receptor (β2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the β2-AR gene (Gln27Glu β2 and Arg16Gly β2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly β2 and Gln27Glu β2 polymorphisms and between β2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of β2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals. PMID:25755837

  19. The Brachyury Gly177Asp SNP Is not Associated with a Risk of Skull Base Chordoma in the Chinese Population

    Directory of Open Access Journals (Sweden)

    Zhen Wu

    2013-10-01

    Full Text Available A recent chordoma cancer genotyping study reveals that the rs2305089, a single nucleotide polymorphism (SNP located in brachyury gene and a key gene in the development of notochord, is significantly associated with chordoma risk. The brachyury gene is believed to be one of the key genes involved in the pathogenesis of chordoma, a rare primary bone tumor originating along the spinal column or at the base of the skull. The association between the brachyury Gly177Asp single nucleotide polymorphism (SNP and the risk of skull base chordoma in Chinese populations is currently unknown. We investigated the genotype distribution of this SNP in 65 skull-base chordoma cases and 120 healthy subjects. Comparisons of the genotype distributions and allele frequencies did not reveal any significant difference between the groups. Our data suggest that the brachyury Gly177Asp SNP is not involved in the risks of skull-base chordoma, at least in the Chinese population.

  20. Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2010-01-01

    We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N-terminal ......We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso...

  1. Sostenere le produzioni cinematografiche: vantaggi fiscali e di immagine per gli investitori / Sustaining cinematographic productions: fiscal and image opportunities for investors

    Directory of Open Access Journals (Sweden)

    Katia Giusepponi

    2016-05-01

    Full Text Available Questo contributo è focalizzato su organizzazioni non appartenenti al settore cinematografico, osservate nel loro ruolo di investitori esterni. L’importanza del valore collettivo di sostenere le produzioni cineaudiovisive è alla base del presente lavoro. Tuttavia la nostra attenzione è qui rivolta, da un lato, a studiare i vantaggi dell’investimento per l’azienda esterna, dall’altro, ad analizzarne i rischi nella prospettiva di una sempre più chiara consapevolezza di scelta. Dall’analisi di strumenti, dinamiche e dati emergono opportunità rilevanti per l’azienda, insieme a condizioni importanti per utilizzarle con successo. È essenziale che l’organizzazione proceda senza improvvisare, curando, da un lato, un approccio alla pianificazione e alla dettagliata valutazione del progetto, dall’altro, flessibilità e apertura nelle interazioni con gli altri interlocutori, interazioni che devono essere orientate al raggiungimento dell’equilibrio migliore a livello collettivo e individuale. Soprattutto, è necessario che l’azienda proceda nel contesto di un percorso strategico solido e coerente, perché un progetto di film può valorizzare l’identità aziendale ma non risolvere incertezze a questo riguardo.   This contribution focuses on organisations that are not in the cinema industry, studied in their role as external investors. The importance of the collective value of sustaining cine audio visual productions is at the basis of this work. Nonetheless, our attention is oriented, on one hand, to study the investment advantages for the external organization, on the other, to analyse the risks of this investment in the perspective of an increasingly clear choice. From the analysis of tools, dynamics and data, relevant opportunities for the organisation emerge, together with important conditions for their successful implementation. It is essential that the organization proceed without improvising, following, on one side, an

  2. Affinity capillary electrophoresis and density functional theory study of noncovalent interactions of cyclic peptide [Gly(6)]-antamanide with small cations

    Czech Academy of Sciences Publication Activity Database

    Pangavhane, Sachin; Böhm, S.; Makrlík, E.; Ruzza, P.; Kašička, Václav

    2017-01-01

    Roč. 38, č. 16 (2017), s. 2025-2033 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA15-01948S Institutional support: RVO:61388963 Keywords : affinity capillary electrophoresis * cesium complex * density functional theory * [Gly(6)]-antamanide * rubidium complex * stability constants Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.744, year: 2016

  3. Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements

    OpenAIRE

    Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

    2015-01-01

    The limb skeletal elements that have unique morphology and distinct locations are developed from limb progenitors, derived from the lateral plate mesoderm. These skeletal elements arise during limb development. In this study, we show genetic evidence that function of Sall4 is essential prior to limb outgrowth for development of the anterior-proximal skeletal elements. Furthermore, genetic interaction between Sall4 and Gli3 is upstream of establishing Shh (Sonic hedgehog) expression, and there...

  4. del, Escher, Bach un'eterna ghirlanda brillante : una fuga metaforica su menti e macchine nello spirito di Lewis Carroll

    CERN Document Server

    Hofstadter, Douglas R

    1984-01-01

    Il libro che ha svelato a una immensa quantità di lettori, in tutto il mondo, gli incanti e le trappole di un’Eterna Ghirlanda Brillante i cui fili si chiamano intelligenza artificiale, macchina di Turing, teorema di Gödel. Una «fuga metaforica» nel variegato mondo che si dispiega fra la mente, il cervello e i computer

  5. Book review. Gli animali, l'uomo e l'ambiente. (a cura di Giorgio Battelli, Raffaella Baldelli, Fabio Ostanello, Santino Prosperi

    Directory of Open Access Journals (Sweden)

    Manuel Graziani

    2013-12-01

    à di produzione e commercializzazione di alimenti di origine animale, alle emergenze di tipo sanitario, alle nuove istanze dei consumatori e degli amministratori pubblici. La prima parte "La storia e i concetti" si sofferma in particolare sull'evoluzione della SPV in Italia, sulle zoonosi, sul rapporto uomo-animale anche in ambito urbano con l'ultimo contributo relativo all'igiene urbana veterinaria. La seconda parte "Le attività" passa in rassegna i Servizi Veterinari pubblici del Paese, i NAS, gli Enti scientifici (tra cui IIZZSS e ISS fino a trattare attività quali la sicurezza alimentare, le emergenze non epidemiche, il benessere animale e la pet therapy. Nella terza e ultima parte "Le sfide" ci si interroga sul ruolo sociale della medicina veterinaria, sul concetto di medicina unica, sull'etica nella sperimentazione animale, sulla formazione, l'educazione e la comunicazione.

  6. Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-01-06

    Systematic substitution of His(6) residue using non-selective hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)) as the template led to the identification of Bu-Atc(6)(2-aminotetraline-2-carboxylic acid)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which showed moderate selectivity towards hMC4R over hMC1R. Further SAR studies resulted in the discovery of Penta-5-BrAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and Penta-5-Me(2)NAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which are potent hMC4R agonists and are inactive in hMC1R, hMC3R and hMC5R agonist assays.

  7. Intestinal drug transport via the proton-coupled amino acid transporter PAT1 (SLC36A1) is inhibited by Gly-X(aa) dipeptides

    DEFF Research Database (Denmark)

    Frølund, Sidsel; Langthaler, Louise; Kall, Morten A

    2012-01-01

    -Sar as substrates of the amino acid transporter PAT1. The aim of the present study is to investigate if other Gly-containing dipeptides interact with PAT1, and whether they can inhibit PAT1 mediated drug absorption, in vitro and in vivo. The in vitro methods included two-electrode voltage clamp measurements on h...... of different dipeptides. The in vivo part consisted of a pharmacokinetic study in rats following oral administration of gaboxadol and preadministration of 200 mg/kg dipeptide. The results showed that in hPAT1 expressing oocytes Gly-Tyr, Gly-Pro, and Gly-Phe inhibited currents induced by drug substances......, the present study identifies selected dipeptides as inhibitors of PAT1 mediated drug absorption in various in vitro models....

  8. Activity of Metabotropic Glutamate Receptor 4 Suppresses Proliferation and Promotes Apoptosis With Inhibition of Gli-1 in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Zhichao Zhang

    2018-05-01

    Full Text Available Glioblastoma multiforme (GBM is the most lethal glioma variant in the adult brain and among the deadliest of human cancers. Increasing evidence has shown that metabotropic glutamate receptor subtype 4 (mGluR4 expression may play roles in regulating the growth of neural stem cells as well as several cancer cell lines. Here, we investigated the effects of mGluR4 on the growth and apoptosis of the LN229 GBM cell line. Involvement of Gli-1, one of the key transcription factors in the sonic Hedgehog (SHH signaling pathway, was further explored. In this study, mGluR4 was activated using selective agonist VU0155041; and gene-targeted siRNAs were used to generate loss of function of mGluR4 and Gli-1 in LN229 cells. The results demonstrated that LN229 cells expressed mGluR4 and the agonist VU0155041 decreased cell viability in a dose- and time-dependent manner. Activation of mGluR4 inhibited cyclin D1 expression, activated pro-caspase-8/9/3, and disrupted the balance of Bcl-2/Bax expression, which indicated cell cycle arrest and apoptosis of LN229 cells, respectively. Furthermore, Gli-1 expression was reduced by mGluR4 activation in LN229 cells, and downregulation of Gli-1 expression by gene-targeted siRNA resulted in both inhibition of cell proliferation and promotion of apoptosis. Moreover, VU0155041 treatment substantially blocked SHH-induced cyclin D1 expression and cell proliferation, while increasing TUNEL-positive cells and the activation of apoptosis-related proteins. We concluded that activation of mGluR4 expressed in LN229 cells could inhibit GBM cell growth by decreasing cell proliferation and promoting apoptosis. Further suppression of intracellular Gli-1 expression might be involved in the action of mGluR4 on cancer cells. Our study suggested a novel role of mGluR4, which might serve as a potential drug target for control of GBM cell growth.

  9. Analysis of the Gli-D2 locus identifies a genetic target for simultaneously improving the breadmaking and health-related traits of common wheat.

    Science.gov (United States)

    Li, Da; Jin, Huaibing; Zhang, Kunpu; Wang, Zhaojun; Wang, Faming; Zhao, Yue; Huo, Naxin; Liu, Xin; Gu, Yong Q; Wang, Daowen; Dong, Lingli

    2018-05-11

    Gliadins are a major component of wheat seed proteins. However, the complex homoeologous Gli-2 loci (Gli-A2, -B2 and -D2) that encode the α-gliadins in commercial wheat are still poorly understood. Here we analyzed the Gli-D2 locus of Xiaoyan 81 (Xy81), a winter wheat cultivar. A total of 421.091 kb of the Gli-D2 sequence was assembled from sequencing multiple bacterial artificial clones, and 10 α-gliadin genes were annotated. Comparative genomic analysis showed that Xy81 carried only eight of the α-gliadin genes of the D genome donor Aegilops tauschii, with two of them each experiencing a tandem duplication. A mutant line lacking Gli-D2 (DLGliD2) consistently exhibited better breadmaking quality and dough functionalities than its progenitor Xy81, but without penalties in other agronomic traits. It also had an elevated lysine content in the grains. Transcriptome analysis verified the lack of Gli-D2 α-gliadin gene expression in DLGliD2. Furthermore, the transcript and protein levels of protein disulfide isomerase were both upregulated in DLGliD2 grains. Consistent with this finding, DLGliD2 had increased disulfide content in the flour. Our work sheds light on the structure and function of Gli-D2 in commercial wheat, and suggests that the removal of Gli-D2 and the gliadins specified by it is likely to be useful for simultaneously enhancing the end-use and health-related traits of common wheat. Because gliadins and homologous proteins are widely present in grass species, the strategy and information reported here may be broadly useful for improving the quality traits of diverse cereal crops. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  10. Efficient Absorption of X-Hydroxyproline (Hyp)-Gly after Oral Administration of a Novel Gelatin Hydrolysate Prepared Using Ginger Protease.

    Science.gov (United States)

    Taga, Yuki; Kusubata, Masashi; Ogawa-Goto, Kiyoko; Hattori, Shunji

    2016-04-13

    Recent studies have reported that oral intake of gelatin hydrolysate has various beneficial effects, such as reduction of joint pain and lowering of blood sugar levels. In this study, we produced a novel gelatin hydrolysate using a cysteine-type ginger protease having unique substrate specificity with preferential peptide cleavage with Pro at the P2 position. Substantial amounts of X-hydroxyproline (Hyp)-Gly-type tripeptides were generated up to 2.5% (w/w) concomitantly with Gly-Pro-Y-type tripeptides (5%; w/w) using ginger powder. The in vivo absorption of the ginger-degraded gelatin hydrolysate was estimated using mice. The plasma levels of collagen-derived oligopeptides, especially X-Hyp-Gly, were significantly high (e.g., 2.3-fold for Glu-Hyp-Gly, p < 0.05) compared with those of the control gelatin hydrolysate, which was prepared using gastrointestinal proteases and did not contain detectable X-Hyp-Gly. This study demonstrated that orally administered X-Hyp-Gly was effectively absorbed into the blood, probably due to the high protease resistance of this type of tripeptide.

  11. Monitoraggio in continuo di strutture e del territorio mediante la tecnologia GNSS

    OpenAIRE

    Poluzzi, Luca

    2016-01-01

    Al giorno d’oggi, la tecnologia GNSS può essere uno strumento utile, non solo in ambito di navigazione, ma anche per applicazioni di posizionamento di precisione come il monitoraggio di strutture o del territorio. Questa tecnica permette un controllo in continuo, anche da remoto, e ha un costo relativamente basso sia per quanto riguarda le strumentazioni che per gli aspetti di materializzazione e mantenimento. Nell’ottica di utilizzare la tecnologia GNSS per applicazioni di monitoraggio, il p...

  12. Alle origini della conservazione del paesaggio in Belgio: il contributo originale di Louis Van der Swaelmen

    OpenAIRE

    Rapalo, Maria Chiara

    2017-01-01

    La ricerca che si propone si inserisce nell’ambito di alcuni studi condotti nel quadro di una collaborazione Italia-Belgio sulle tematiche della conservazione e tutela dei beni architettonici e del paesaggio, collegate e talvolta intrecciate a quelle dell’urbanistica. Essa nasce dall’esigenza di comprendere gli interessanti e meno approfonditi contributi che, in ambito belga, hanno concorso al delinearsi delle attuali linee di orientamento internazionale nel campo della conservazione e della ...

  13. Real Estate Crowdfunding. Un’innovazione finanziaria per gli investimenti immobiliari

    Directory of Open Access Journals (Sweden)

    Giacomo Morri

    2016-12-01

    Full Text Available Questo articolo presenta una panoramica del crowdfunding e delle sue potenziali applicazioni al settore immobiliare. La crisi economica globale del 2008 ha condotto a una paralisi dell’economia che ha comportato la riduzione della fiducia nel sistema bancario e nei servizi finanziari in generale. Nell’ultimo decennio una delle tecniche di finanziamento più rivoluzionaria è stata il crowdfunding, cioè la possibilità di essere finanziati dalla “folla” (crowd attraverso l’utilizzo di Internet. Il crowdfunding nel settore immobiliare ha origine negli Stati Uniti nel 2012 con il Jumpstart Our Business Start-up Act (JOBS Act, dove da allora si sta sviluppando a ritmi elevati. In Italia, il crowdfunding per progetti nel settore immobiliare non si è ancora sviluppato in quanto la legge in concreto non ne consente l’utilizzo; tuttavia esistono alcune piattaforme che stanno utilizzando il concetto in modi differenti, raccogliendo un certo interesse. Il Real Estate Crowdfunding può rappresentare un’interessante opportunità per i privati che vogliono investire nel settore immobiliare, ma non hanno abbastanza capitale per partecipare a grandi transazioni o esperienza nella gestione. In quest’articolo, dopo un’iniziale descrizione del crowdfunding in generale, ci si focalizza sulla sua applicazione nel settore immobiliare, analizzando il mercato statunitense dove vi sono le piattaforme più sviluppate. Infine, si presenta una panoramica del mercato italiano, spiegando le normative e i limiti del crowdfunding e descrivendo la modalità operativa sviluppata da alcune piattaforme per superare legalmente tali limitazioni. Negli Stati Uniti sono già operative oltre 125 piattaforme con una raccolta superiore a un miliardo di dollari; in Italia invece ci sono ancora limiti per le start-up che si occupano di crowdfunding e sono state create solo poche piattaforme che operano con un modello parzialmente diverso.

  14. Trasmissione del sapere musicale e storia della cultura europea nei primi decenni del secolo XV

    Directory of Open Access Journals (Sweden)

    Matteo Nanni

    2013-12-01

    Full Text Available L’evoluzione storico-musicale nella prima metà del Quattrocento è caratterizzata dall’internazionalizzazione della cultura musicale europea ed si pone in continuità con il processo culturale del primo umanesimo. La categoria di ‘evoluzione’ e l’idea stessa di ‘rinascita’, ovvero quella “leggenda di un progresso” (Martin Le Franc, Johannes Tinctoris discussa da Reinhard Strohm, sono concetti che oggi devono essere letti non soltanto nel senso di una omologazione stilistica, ma anche come aspetto distintivo di una ricerca d’identità culturale. Anche dal punto di vista storico-musicale siamo di fronte alla costituzione di un nuovo gusto europeo nato dalla fusione di stili e di pratiche locali che si espanderà, grazie alla trasmissione delle compilazioni manoscritte, per tutto il continente e al quale aderiranno, in maniera disomogenea, anche compositori di regioni più remote.Il Concilio di Basilea non costituisce solo un dato storico circoscrivibile agli anni in cui si svolse il sinodo, così come non è da considerarsi solo un fatto empirico riguardante la sola città della Svizzera settentrionale. Esso deve piuttosto essere assunto come un evento paradigmatico per la storia della cultura del Quattrocento. Gli incontri fra intellettuali ed artisti, l’interazione fra musicisti di diverse regioni europee che si incontravano grazie ai frequentissimi spostamenti delle corti e delle cappelle, fanno del Concilio la piattaforma virtuale sia per la ricerca di una nuova identità culturale sia per la nascita di nuovi repertori e pratiche musicali. Il Concilio trascende quindi i confini contingenti della città di Basilea trasformandosi in una vera e propria “dinamica culturale” in cui i singoli individui contribuiscono alla continua trasmissione e fusione di esperienze musicali diventando vettori di una nuova mentalità musicale che raggiunse anche gli angoli più remoti dell’Europa.

  15. La ricostruzione grafica del pavimento musivo di una villa romana

    Directory of Open Access Journals (Sweden)

    Caterina Gattuso

    2015-01-01

    Full Text Available Nel processo di analisi conoscitiva finalizzato alla conservazione e/o al restauro di un manufatto storico, la documentazione grafica offre un contributo importante ai fini della redazione del quadro anamnesico. Essa costituisce uno strumento conoscitivo che, nel rappresentare e registrare lo stato di conservazione nonché gli eventuali interventi di restauro cui il bene è stato sottoposto, permette di completare e di integrare le informazioni già ottenute mediante il dossier fotografico. In questo contesto si vuole dimostrare l’importanza del disegno informatico, da intendere come strumento utile per l’elaborazione di un corretto piano diagnostico, illustrando la ricostruzione grafica di una complessa pavimentazione musiva che decora un particolare ambiente di una villa di epoca romana posta sulle rive del lago d’Esaro nel comune di Roggiano Gravina (CS, ottenuta attraverso l’uso di un particolare software di design grafico e disegno vettoriale.

  16. Aristotele, Einstein e gli altri i grandi scienziati tra pensiero e vita quotidiana

    CERN Document Server

    Fischer, Ernst Peter

    1997-01-01

    Abbiamo spesso un'idea confusa di quelle che sono state le vite degli uomini che hanno consacrato all'impresa scientifica le loro migliori energie. Eppure, non solo nell'arte e nella filosofia, ma anche nella scienza "lo stile è l'uomo" e la psicologia del singolo scienziato può rivelarsi il miglior aiuto per capire la logica della scoperta scientifica. Questa è una "storia della scienza raccontata agli amici davanti al caminetto", come l'autore stesso definisce la propria opera. Che non è soltanto una ricostruzione puntuale delle svolte principali che hanno portato alla scienza contemporanea, ma un racconto delle vicende personali di tutti quegli scienziati che sono stati divorati dalla passione del conoscere.

  17. Synthesis of Fluorine-18 Labeled Glucose-Lys-Arg-Gly-Asp-D-Phe as a Potential Tumor Imaging Agent

    International Nuclear Information System (INIS)

    Lee, Kyo Chul; Kim, Ji Sun; Sung, Hyun Ju; Jung, Jae Ho; An, Gwang Il; Chi, Dae Yoon; Lee, Byung Chul; Moon, Byung Seok; Choi, Tae Hyun; Chuna, Kwon Soo

    2005-01-01

    The α v β 3 integrin is an important receptor affecting tumor growth, metastatic potential on proliferating endothelial cells as well as on tumor cells of various origin, tumor-induced angiogenesis could be blocked by antagonizing the α v β 3 integrin with RGD. Therefore, α v β 3 integrin is a target for angiogenesis imaging that might be useful in assessing tumor-induced angiogenesis and identifying tumor metastasis. To design potent radiotracer for imaging angiogenesis containing a cRGD moiety should include low hepatic uptake in vivo. Tripeptide Arg-Gly-Asp (RGD), naturally existed in extracellular matrix proteins, is known to be the primary binding site of the α v β 3 integrin. The imaging of α v β 3 receptor expression will give the information of the metastatic ability of the tumor which is not available by [ 18 F]FDG. Our interest in developing new radiopharmaceuticals for in vivo visualization of angiogenesis has led us to synthesize derivatives of cRGD (cyclic arginineglycine-aspartic acid) that contains glucose moiety. Because sugar-protein interaction is a key step in metastasis and angiogenesis, it has also been proposed to play an intriguing role in imaging of tumor. We designed and synthesized two fluorine-18 labeled RGD glycopeptides . N-fluorobenzyl-diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([ 18 F]fluorobenzyl-glucose-KRGDf, and Nfluorobenzoyl- diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([ 18 F]fluorobenzoyl-glucose-KRGDf, from same precursor as a diagnostic tumor imaging agent for positron emission tomography (PET). Fluorine-18 labeled cRGD glycopeptides were prepared using two different simple labeling methods: one is reductive alkylation of an amine with [ 18 F]fluorobenzaldehyde and the other is amide condensation with [ 18 F]fluorobenzoic acid

  18. Studio di una classe notevole di anelli dotata di inverso generalizzato

    Directory of Open Access Journals (Sweden)

    Maria Scafati Tallini

    2008-11-01

    Full Text Available We study a remarkable class of rings, which we call corpids, that is the rings, different from zero, (K;+; .; such that (K; . is an inverse semi-group (or groupid, which is the name given by G. Tallini [4]. The inverse semigroup has been defined and called generalized group, indipendently by Viktor Vladimirovich Vagner [6] in the Soviet Union and by Gordon Preston in the Great Britain [3].

  19. Expression of the glioma-associated oncogene homolog 1 (gli1 in advanced serous ovarian cancer is associated with unfavorable overall survival.

    Directory of Open Access Journals (Sweden)

    Alessandra Ciucci

    Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma as well as pancreas, colorectal, and prostate carcinomas. Here we investigated the role of the transcription factor Gli1 in ovarian cancer. To this end, the expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58 on cell proliferation and on Hh target gene expression were also assessed. Results obtained showed that epithelial cells in ovarian cancer tissue express significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where the protein was almost undetectable. In addition, multivariate analysis showed that nuclear Gli1 was independently associated to poor survival in advanced serous ovarian cancer patients (HR = 2.2, 95%CI 1.0-5.1, p = 0.04. In vitro experiments demonstrated Gli1 expression in the three ovarian carcinoma cell lines tested, A2780, SKOV-3 and OVCAR-3. Remarkably, although KAAD-cyclopamine led to decreased cell proliferation, this treatment did not inhibit hedgehog target gene expression in any of the three ovarian cancer cell lines, suggesting that the inhibition of cell proliferation was a nonspecific or toxic effect. In line with these data, no differences on cell proliferation were observed when cell lines were treated with GANT58. Overall, our clinical data support the role of Gli1 as a prognostic marker in advanced serous ovarian cancer and as a possible therapeutic target in this disease. However, our in vitro findings draw attention to the need for selection of appropriate experimental models that accurately represent human tumor for testing future therapies involving Hh pathway inhibitors.

  20. Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions.

    Science.gov (United States)

    Musante, Veronica; Summa, Maria; Cunha, Rodrigo A; Raiteri, Maurizio; Pittaluga, Anna

    2011-05-01

    Rat hippocampal glutamatergic terminals possess NMDA autoreceptors whose activation by low micromolar NMDA elicits glutamate exocytosis in the presence of physiological Mg(2+) (1.2 mM), the release of glutamate being significantly reduced when compared to that in Mg(2+)-free condition. Both glutamate and glycine were required to evoke glutamate exocytosis in 1.2 mM Mg(2+), while dizocilpine, cis-4-[phosphomethyl]-piperidine-2-carboxylic acid and 7-Cl-kynurenic acid prevented it, indicating that occupation of both agonist sites is needed for receptor activation. D-serine mimicked glycine but also inhibited the NMDA/glycine-induced release of [(3H]D-aspartate, thus behaving as a partial agonist. The NMDA/glycine-induced release in 1.2 mM Mg(2+) strictly depended on glycine uptake through the glycine transporter type 1 (GlyT1), because the GlyT1 blocker N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine hydrochloride, but not the GlyT2 blocker Org 25534, prevented it. Accordingly, [(3)H]glycine was taken up during superfusion, while lowering the external concentration of Na(+), the monovalent cation co-transported with glycine by GlyT1, abrogated the NMDA-induced effect. Western blot analysis of subsynaptic fractions confirms that GlyT1 and NMDA autoreceptors co-localize at the pre-synaptic level, where GluN3A subunits immunoreactivity was also recovered. It is proposed that GlyT1s coexist with NMDA autoreceptors on rat hippocampal glutamatergic terminals and that glycine taken up by GlyT1 may permit physiological activation of NMDA pre-synaptic autoreceptors. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  1. X-linked Alport syndrome associated with a synonymous p.Gly292Gly mutation alters the splicing donor site of the type IV collagen alpha chain 5 gene.

    Science.gov (United States)

    Fu, Xue Jun; Nozu, Kandai; Eguchi, Aya; Nozu, Yoshimi; Morisada, Naoya; Shono, Akemi; Taniguchi-Ikeda, Mariko; Shima, Yuko; Nakanishi, Koichi; Vorechovsky, Igor; Iijima, Kazumoto

    2016-10-01

    X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the type IV collagen alpha chain 5 gene (COL4A5). Although many COL4A5 mutations have previously been identified, pathogenic synonymous mutations have not yet been described. A family with XLAS underwent mutational analyses of COL4A5 by PCR and direct sequencing, as well as transcript analysis of potential splice site mutations. In silico analysis was also conducted to predict the disruption of splicing factor binding sites. Immunohistochemistry (IHC) of kidney biopsies was used to detect α2 and α5 chain expression. We identified a hemizygous point mutation, c.876A>T, in exon 15 of COL4A5 in the proband and his brother, which is predicted to result in a synonymous amino acid change, p.(Gly292Gly). Transcript analysis showed that this mutation potentially altered splicing because it disrupted the splicing factor binding site. The kidney biopsy of the proband showed lamellation of the glomerular basement membrane (GBM), while IHC revealed negative α5(IV) staining in the GBM and Bowman's capsule, which is typical of XLAS. This is the first report of a synonymous COL4A5 substitution being responsible for XLAS. Our findings suggest that transcript analysis should be conducted for the future correct assessment of silent mutations.

  2. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

    Science.gov (United States)

    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  3. Il giudice Wyndham e gli spettacoli per l’intrattenimento di Elisabetta I a Norwich

    Directory of Open Access Journals (Sweden)

    F. Minetti

    2012-08-01

    Full Text Available ENThe fabrication of a popery charge, which in August 1578 Edward Rokewood was subjected to while hosting Queen Elizabeth in the East Anglia, has been dubiously dealt with in the field of gender studies (Dovey, 1996; Brownlow, 2003 or overrated by historians of Puritanism to corroborate how the queen’s Privy Council ruled the kingdom through a manipulation of her weak will and female simple-mindedness (MacCulloch, 1986; Collinson, 2007. My paper proposes to substantiate how the intrigue against Rokewood arose from a wider social group of officers than the Lord Chamberlain Sussex and the royal favourite Leicester’s clique. Some days after the papist had been jailed in the castle of Norwich, mayor and aldermen commissioned public speeches and a composite biblical pageantry which, though allusively, both staged Rokewood’s conspiracy in favour of the Spanish king’s invasion and urged Elizabeth to inflict a death penalty. But the queen did not only turn a deaf ear to these pressures, presiding over the trial proceedings to get a time of forced reform for Rokewood. Some letters from the judge of assizes Francis Wyndham will help me to suggest that she was nor manipulated neither prevented from seeing that the case had been invented by the municipal corporation to advoke their bishop’s means of control and persecution of dissent.ITL’invenzione di un’accusa di papismo, che ad agosto del 1578 Edward Rokewood subisce mentre ospita la regina Elisabetta nella regione orientale dell’Anglia, è discussa con grande scetticismo nel settore dei gender studies (Dovey, 1996, pp. 54-55; Brownlow, 2003, pp. 11-13, oppure sopravvalutata da storici della cultura puritana convinti che il Privy Council tenga le redini del regno manipolando volontà e credulità della regina (MacCulloch, 1986, pp. 218-219; Collinson, 2007, p. 131. Questo paper si propone di documentare come la macchinazione ai danni di Rokewood si estenda ben oltre la cerchia del

  4. Riflessioni sulle pratiche educative osservate in un nido del Centro Nascita Montessori

    Directory of Open Access Journals (Sweden)

    Laura Franceschini

    2010-02-01

    Full Text Available L’articolo presenta una ricerca basata sull’osservazione di un contesto educativo di ispirazione montessoriana. La ricerca intendeva mettere in luce gli atteggiamenti, le proposte e le strategie delle educatrici, e le risposte dei bambini a queste sollecitazioni. Il testo si articola in una introduzione metodologica che illustra il tipo di servizio educativo, la metodologia di osservazione adottata e la traccia che ha guidato le osservazioni; seguono alcune considerazioni sull’autonomia del bambino, l’attenzione al singolo bambino e la cura del bambino, emerse dalla analisi delle osservazioni; conclude l’articolo la trascrizione di una delle tre osservazioni condotte.

  5. Il Toyota way e la crisi. Tornare alle origini del lean management per sopravvivere e prosperare

    OpenAIRE

    A. Camuffo; D. Weber

    2009-01-01

    Nel settore automobilistico gli occhi sono tutti puntati sui bailouts delle Big Three americane e sugli interventi statali a supporto dei produttori europei, oltre che sulla scommessa rappresentata dall’operazione FIAT-Chrysler. Ma la domanda più importante per capire dove andrà il settore auto è cosa accadrà a Toyota. È questa la vera domanda che ci si deve porre, perché il Toyota Way è importante, al di là del suo destino individuale, per il destino del settore automobi...

  6. Gli effetti dell'attrito sulla stima della disuguaglianza in Italia

    OpenAIRE

    F. Biagi; A. Giraldo; E. Rettore

    2009-01-01

    Il volume contiene i rapporti finali di un'articolata ricerca su alcune significative dimensioni della disuguaglianza nell'Italia di oggi: la povertà e l'evoluzione recente della distribuzione del reddito; la condizione di salute e la sua relazione con le caratteristiche socio-economiche degli individui; le disparità nella disponibilità della casa e nelle situazioni abitative. La ricerca, condotta nell'ambito dell'"Osservatorio sulle disuguaglianze sociali", è stata coordinata da un'equipe in...

  7. Aspetti tributari dei crediti d’impresa contabilizzati secondo gli Ias/Ifrs: prime riflessioni sistematiche

    OpenAIRE

    A. CONTRINO

    2011-01-01

    1. La disciplina dei crediti d’impresa nei principi contabili internazionali. – 1.1. Costo ammortizzato, valore di presumibile realizzo e «perdite da valutazione». – 1.2. Derecognition, «realizzo» ai fini IAS/IFRS e «perdite da cancellazione». – 2. I nuovi termini di rilevanza fiscale dei crediti IAS/IFRS in forza del principio di derivazione «rafforzata». – 2.1. Sui confini dell’area di determinazione dell’imponibile riservata dall’art. 83 ai principi contabili internazionali. – 2.2. Il nuov...

  8. Molecular Analysis of Gli3, Ihh, Rab23, and Jag1 in a Rabbit Model of Craniosynostosis: Likely Exclusion as the Loci of Origin.

    Science.gov (United States)

    Gilbert, James R; Taylor, Gwen M; Losee, Joseph E; Mooney, Mark P; Cooper, Gregory M

    2018-03-01

    Craniosynostosis (CS) involves the premature fusion of one or more cranial sutures. The etiology of CS is complex and mutations in more than 50 distinct genes have been causally linked to the disorder. Many of the genes that have been associated with CS in humans play an essential role in tissue patterning and early craniofacial development. Among these genes are members of the Hedgehog (HH) and Notch signal transduction pathways, including the GLI family member Gli3, Indian Hedgehog ( Ihh), the RAS oncogene family member Rab23, and the Notch ligand JAGGED1 ( Jag1). We have previously described a colony of rabbits with a heritable pattern of coronal suture synostosis, although the genetic basis for synostosis within this model remains unknown. The present study was performed to determine if coding errors in Gli3, Ihh, Rab23, or Jag1 could be causally linked to craniosynostosis in this unique animal model. Sequencing of cDNA templates was performed using samples obtained from wild-type and craniosynostotic rabbits. Several nucleotide polymorphisms were identified in Gli3, Ihh, and Rab23, although these variants failed to segregate by phenotype. No nucleotide polymorphisms were identified in Jag1. These data indicate that the causal locus for heritable craniosynostosis in this rabbit model is not located within the protein coding regions of Gli3, Ihh, Rab23, or Jag1.

  9. Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

    Science.gov (United States)

    Richardson, Adam; Muir, Lewis; Mousdell, Sasha; Sexton, Darren; Jones, Sarah; Howl, John; Ross, Kehinde

    2018-01-30

    Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L -1 , MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.

  10. The recent multi-ethnic global lung initiative 2012 (GLI2012) reference values don't reflect contemporary adult's North African spirometry.

    Science.gov (United States)

    Ben Saad, Helmi; El Attar, Mohamed Nour; Hadj Mabrouk, Khaoula; Ben Abdelaziz, Ahmed; Abdelghani, Ahmed; Bousarssar, Mohamed; Limam, Khélifa; Maatoug, Chiraz; Bouslah, Hmida; Charrada, Ameur; Rouatbi, Sonia

    2013-12-01

    The applicability of the recent multi-ethnic reference equations derived by the ERS Global Lung Initiative (ERS/GLI) in interpreting spirometry data in North African adult subjects has not been studied. To ascertain how well the recent ERS/GLI reference equations fit contemporary adult Tunisian spirometric data. Spirometric data were recorded from 1192 consecutive spirometry procedures in adults aged 18-60 years. Reference values and lower limits of normality (LLN) were calculated using the local and the ERS/GLI reference equations. Applied definitions: large airway obstructive ventilatory defect (LAOVD): FEV1/FVC contemporary Tunisian spirometry. Using Tunisian reference equations, 71.31%, 6.71% and 19.04% of spirometry records were interpreted as normal, and as having, LAOVD and TRVD, respectively. Using the ERS/GLI reference equations, these figures were respectively, 85.82%, 4.19% and 8.39%. The mean ± SD Z-scores for the contemporary healthy North African subject's data were -0.55 ± 0.87 for FEV1, -0.62 ± 0.86 for FVC and 0.10 ± 0.73 for FEV1/FVC. The present study don't recommend the use of the recent ERS/GLI reference equations to interpret spirometry in North African adult population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Sonic hedgehog (SHH) and glioblastoma-2 (Gli-2) expressions are associated with poor jaundice-free survival in biliary atresia.

    Science.gov (United States)

    Jung, Hae Yoen; Jing, Jin; Lee, Kyoung Bun; Jang, Ja-June

    2015-03-01

    Biliary atresia (BA) causes biliary obstruction in neonates. Although the Kasai operation can successfully treat certain BA cases, many patients exhibit recurrent jaundice and secondary biliary cirrhosis requiring liver transplantation. Consequently, studies of the prognostic factors of the Kasai operation are needed. Accordingly, sonic hedgehog (SHH) pathway expression at the extrahepatic bile duct (EHBD), an important bile duct repair mechanism, will be investigated via immunohistochemistry in patients with BA to examine the association with post-Kasai operation prognosis. Fifty-seven EHBD specimens were obtained during Kasai operations from 1992 to 2009. The SHH, patched (PTCH), and glioblastoma-2 (Gli-2) immunohistochemical staining results were analyzed quantitatively. Overall, 57.9% of patients had bile flow normalization after the Kasai operation; 43.1% did not. High preoperative serum total bilirubin, direct bilirubin, and aspartate aminotransferase levels were associated with sustained jaundice post-Kasai operation, as was an age ≥65days at the time of surgery (all pjaundice relapse. Strong Gli-2 and SHH expression in the EHBD might be a poor prognostic factor in Kasai operation-treated patients with BA. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.

    Science.gov (United States)

    Dong, Guang-Zhi; Jeong, Ji Hye; Lee, Yu-Ih; Lee, So Yoon; Zhao, Hui-Yuan; Jeon, Raok; Lee, Hwa Jin; Ryu, Jae-Ha

    2017-04-01

    Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

  13. Analysis of PGC-1α variants Gly482Ser and Thr612Met concerning their PPARγ2-coactivation function

    International Nuclear Information System (INIS)

    Nitz, Inke; Ewert, Agnes; Klapper, Maja; Doering, Frank

    2007-01-01

    Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a cofactor involved in adaptive thermogenesis, fatty acid oxidation, and gluconeogenesis. Dysfunctions of this protein are likely to contribute to the development of obesity and the metabolic syndrome. This is in part but not definitely confirmed by results of population studies. The aim of this study was to investigate if common genetic variants rs8192678 (Gly482Ser) and rs3736265 (Thr612Met) in the PGC-1α gene lead to a functional consequence in cofactor activity using peroxisome proliferator-activated receptor-γ 2 (PPARγ2) as interacting transcription factor. Reporter gene assays in HepG2 cells with wildtype and mutant proteins of both PGC1α and PPARγ2 (Pro12Ala, rs1801282) using the acyl-CoA-binding protein (ACBP) promoter showed no difference in coactivator activity. This is First study implicating that the Gly482Ser and Thr612Met polymorphisms in PGC-1α and Pro12Ala polymorphism in PPARγ2 do not affect the functional integrity of these proteins

  14. FORS, Fiber Optics Reflectance Spectroscopy con gli spettrometri miniaturizzati per l’identificazione dei pigmenti

    Directory of Open Access Journals (Sweden)

    Antonino Cosentino

    2014-01-01

    Full Text Available AbstractQuesto articolo riporta i risultati del test di un sistema FORS (Fiber Optics Reflectance Spectroscopy assemblato con componenti Ocean Optics. Questa ditta ha sviluppato una linea di spettrometri miniaturizzati e dal costo estremamente contenuto. Le trascurabili dimensioni e peso di questo sistema FORS lo rendono uno strumento assolutamente adatto alle indagini dell’arte in cantiere. Sono stati testati 54 pigmenti storici in polvere e stesi con gomma arabica, tempera all’uovo, olio e affresco. Il sistema è stato provato su un quadro dell’800 e su opere murali del barocco siciliano.   This paper shows the results of the testing of a FORS (Fiber Optics Reflectance Spectroscopy system assembled with Ocean Optics components and featuring a USB4000 miniaturized and low cost spectrometer. The small dimensions and little weight of this FORS system make it adapt for the specific needs of art examination in the field. 54 historical pigments have been tested both in powder and laid with gum Arabic, egg tempera, linseed oil and fresco. The FORS system was also tested on a 1800s oil painting and on 1700s Sicilian baroque murals and the results compared with multispectral imaging analysis.   

  15. A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians

    DEFF Research Database (Denmark)

    Muller, Yunhua Li; Bogardus, Clifton; Pedersen, Oluf

    2003-01-01

    of the PGC-1 gene predicts a glycine to serine substitution at amino acid 482 and has been associated with type 2 diabetes in a Danish population. In this study, we examined whether this Gly482Ser polymorphism is associated with type 2 diabetes or obesity, or metabolic predictors of these diseases, in Pima...... Indians. There was no association of the Gly482Ser polymorphism with either type 2 diabetes or BMI (n = 984). However, among nondiabetic Pima Indians (n = 183-201), those with the Gly/Gly genotype had a lower mean insulin secretory response to intravenous and oral glucose and a lower mean rate of lipid...

  16. [La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

    Science.gov (United States)

    Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

  17. Potencial del Agua del suelo

    Directory of Open Access Journals (Sweden)

    Bustamante Heliodoro

    1986-12-01

    Full Text Available La energía potencial del agua presenta diferencias de un punto del suelo a otro; esas diferencias son las que originan el movimiento del agua de acuerdo a la tendencia universal de la materia en el sentido de moverse de donde la energía potencial es mayor a donde dicha energía es menor. En el suelo el agua en consecuencia se mueve hacia donde su energía decrece hasta lograr su estado de equilibrio. Se desprende entonces que la cantidad de energía potencial absoluta contenida en el agua, no es importante por sí misma, sino por su relación con la energía en diferentes lugares dentro del suelo. El concepto Potencial de agua del suelo es un criterio para esta energía.

  18. Il comune di Cesena e gli Open Geo Data sugli incidenti stradali

    Directory of Open Access Journals (Sweden)

    Morena Moretti

    2015-02-01

    Full Text Available Il Comune di Cesena svolge dal 2005 una georeferenziazione degli incidenti stradali sui propri territori, raccog liendo una mole di dati che saranno pubblicati su un portale accessibile liberamente. Scopo del portale è informare i cittadini rispetto ai luog hi ad elevato tasso di incidentalità, alla trasparenza dell’ente rispetto agli interventi di sicurezza stradale e alle azioni di controllo nei period i critici. The Municipality of Cesena held since 2005, a georeferencing of road accidents of its territory. Since January 2015 these data will be published on the new open data portal of the City realized with technology StatPortal Open Data. By acting as "data visualization" these open geo data will be accessible via the web with maps, charts and graphs with multiple benefits, from increased knowledge of citizens compared to places with a high accident rate to the transparency of the institution from the measures road safety and control actions during critical periods.

  19. Environmental analysis of natural gas life cycle; Analisi ambientale del ciclo di vita del gas naturale

    Energy Technology Data Exchange (ETDEWEB)

    Riva, A.; D' Angelosante, S.; Trebeschi, C. [Snam SpA, Rome (Italy)

    2000-12-01

    Life Cycle Assessment is a method aimed at identifying the environmental effects connected with a given product, process or activity during its whole life cycle. The evaluation of published studies and the application of the method to electricity production with fossil fuels, by using data from published databases and data collected by the gas industry, demonstrate the importance and difficulties to have reliable and updated data required for a significant life cycle assessment. The results show that the environmental advantages of natural gas over the other fossil fuels in the final use stage increase still further if the whole life cycle of the fuels, from production to final consumption, is taken into account. [Italian] L'analisi del ciclo di vita e' una metodologia che consente di identificare gli effetti ambientali associati ad un prodotto, processo o attivita' lungo il loro ciclo di vita. La valutazione di studi pubblicati e l'applicazione della metodologia alla produzione di energia elettrica da combustibili fossili, utilizzando dati provenienti da banche dati di letteratura e raccolti dall'industria del gas, dimostrano l'importanza e la difficolta' di avere a disposizione dati affidabili ed aggiornati, necessari per un'analisi significativa del ciclo di vita. I risultati mostrano che i vantaggi ambientali del gas naturale rispetto agli altri combustibili fossili nella fase di utilizzo finale, aumentano ulteriormente se si considera l'intero ciclo di vita dei diversi combustibili, dalla produzione al consumo finale.

  20. Edifici di culto e loro pertinenze, consumo del territorio e spending review

    Directory of Open Access Journals (Sweden)

    Federica Botti

    2014-09-01

    Full Text Available assegnista di ricerca nell'Università Alma Mater Studiorum di Bologna, Dipartimento di Scienze GiuridicheContributo sottoposto a valutazione SOMMARIO: 1. Crisi finanziaria dello Stato e nuovo ruolo e funzioni degli edifici di culto - 2. Configurazione degli spazi degli edifici di culto in relazione al loro uso pubblico - 3. Pertinenze “liturgiche” e pertinenze “funzionali”: un primo controllo di spesa - 4. Utilizzazione pubblica delle pertinenze, anche attraverso lo strumento delle convenzioni con gli enti pubblici. Gli edifici di culto di proprietà delle confessioni – 5. Gli edifici di culto di proprietà pubblica gestiti attraverso il F. E. C. -6. Le convenzioni per la concessione dell’utilizzazione a fini di culto di edifici di proprietà pubblica - 7. Il controllo di spesa e il patto di stabilità tra l’attuazione dell’art. 19 Cost., proprietà pubblica di edifici di culto, finanziamenti pubblici per la loro manutenzione/edificazione – 8. Spending review e rivisitazione del rapporto tra consumo del territorio, edifici esistenti e loro utilizzazione/fruizione.

  1. Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

    Science.gov (United States)

    Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; Biswas, Nidhan K; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N; Deb, Sumit; Saha, Suniti K; Chowdhury, Anup K; Ghosh, Subhashish; Rudin, Charles M; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

  2. The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani Santhanakrishnan; Luan, Jian'an; Andersen, Gitte

    2008-01-01

    The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate...... inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised...

  3. Evaluation of the oxidative stress modulation in Drosophila melanogaster strains deficient in endogenous antioxidants and with chronic exposure to casiopeina Cas II-gly and gamma radiation

    International Nuclear Information System (INIS)

    Jimenez V, E. R.

    2013-01-01

    The casiopeinas are a family of coordination compounds with copper metallic center that have shown to have antineoplastic activity. The experimental evidences suggest that its action mechanism is through the generation of free radicals. The casiopeina (Cas II-gly) is believed to causes oxidative damage in the mitochondria, leading to the cellular death. The present study has the purpose to evaluate the antioxidant potential of the tetrapyrroles: cupro-sodica chlorophyllin (CSC), protoporphyrin-Ix (Pp-Ix) and the bilirubin (Bili) against the oxidant action of the Cas II-gly. The present study will also contribute in the characterization of the biological activity of the Cas II-gly. For this purpose is quantifies the effect of these compounds in the enzymes activity, superoxide dismutase (Sod) and catalase (Cat) in wild Drosophila melanogaster strains Canton-S and in the deficient in Sod and Cat. Two protocols were used, in the first male of 1-24 h of age were pre-treated with 0, 0.01, 0.1 and 1 m M of Cas II-gly and later on they were treated with radiation (15 Gy), and the second 69 m M of CSC, Pp-Ix or Bili, during 8 days and later they were treated with 0.1 m M of Cas II-gly during 24 h. The enzymatic activity was measured with the detection packages of enzymes Sod and Cat of Sigma. It was found that none of the three pigments increment the Sod activity but, if they diminished that of Cat (p≤0.007). The three concentrations of Cas II-gly did not increase the Sod activity significantly, only the concentration of 0.1 m M diminishes in 5.6 U the Cat activity (p <0.03) the same as the treatment with 15 Gy of gamma rays (8 U, p <0.004). The Cas II-gly combination 0.1 m M with the pigments does not modify the Sod and Cat activity. These results suggest that the proven pigments act as antioxidants, avoiding the induction of exogenous antioxidants caused by the gamma rays or the Cas II-gly. (Author)

  4. Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures

    Directory of Open Access Journals (Sweden)

    Dong Hongmei

    2010-12-01

    Full Text Available Abstract Background Hedgehog (HH signaling is critical for the expansion of granule neuron precursors (GNPs within the external granular layer (EGL during cerebellar development. Aberrant HH signaling within GNPs is thought to give rise to medulloblastoma (MB - the most commonly-observed form of malignant pediatric brain tumor. Evidence in both invertebrates and vertebrates indicates that cyclic AMP-dependent protein kinase A (PKA antagonizes HH signalling. Receptors specific for the neuropeptide pituitary adenylyl cyclase activating polypeptide (PACAP, gene name ADCYAP1 are expressed in GNPs. PACAP has been shown to protect GNPs from apoptosis in vitro, and to interact with HH signaling to regulate GNP proliferation. PACAP/ptch1 double mutant mice exhibit an increased incidence of MB compared to ptch1 mice, indicating that PACAP may regulate HH pathway-mediated MB pathogenesis. Methods Primary MB tumorsphere cultures were prepared from thirteen ptch1+/-/p53+/- double mutant mice and treated with the smoothened (SMO agonist purmorphamine, the SMO antagonist SANT-1, the neuropeptide PACAP, the PKA activator forskolin, and the PKA inhibitor H89. Gene expression of gli1 and [3H]-thymidine incorporation were assessed to determine drug effects on HH pathway activity and proliferation, respectively. PKA activity was determined in cell extracts by Western blotting using a phospho-PKA substrate antibody. Results Primary tumor cells cultured for 1-week under serum-free conditions grew as tumorspheres and were found to express PAC1 receptor transcripts. Gli1 gene expression was significantly reduced by SANT-1, PACAP and forskolin, but was unaffected by purmorphamine. The attenuation of gli1 gene expression by PACAP was reversed by the PKA inhibitor H89, which also blocked PKA activation. Treatment of tumorsphere cultures with PACAP, forskolin, and SANT-1 for 24 or 48 hours reduced proliferation. Conclusions Primary tumorspheres derived from ptch1+/-/p53

  5. Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures

    International Nuclear Information System (INIS)

    Cohen, Joseph R; Resnick, Daniel Z; Niewiadomski, Pawel; Dong, Hongmei; Liau, Linda M; Waschek, James A

    2010-01-01

    Hedgehog (HH) signaling is critical for the expansion of granule neuron precursors (GNPs) within the external granular layer (EGL) during cerebellar development. Aberrant HH signaling within GNPs is thought to give rise to medulloblastoma (MB) - the most commonly-observed form of malignant pediatric brain tumor. Evidence in both invertebrates and vertebrates indicates that cyclic AMP-dependent protein kinase A (PKA) antagonizes HH signalling. Receptors specific for the neuropeptide pituitary adenylyl cyclase activating polypeptide (PACAP, gene name ADCYAP1) are expressed in GNPs. PACAP has been shown to protect GNPs from apoptosis in vitro, and to interact with HH signaling to regulate GNP proliferation. PACAP/ptch1 double mutant mice exhibit an increased incidence of MB compared to ptch1 mice, indicating that PACAP may regulate HH pathway-mediated MB pathogenesis. Primary MB tumorsphere cultures were prepared from thirteen ptch1 +/- /p53 +/- double mutant mice and treated with the smoothened (SMO) agonist purmorphamine, the SMO antagonist SANT-1, the neuropeptide PACAP, the PKA activator forskolin, and the PKA inhibitor H89. Gene expression of gli1 and [ 3 H]-thymidine incorporation were assessed to determine drug effects on HH pathway activity and proliferation, respectively. PKA activity was determined in cell extracts by Western blotting using a phospho-PKA substrate antibody. Primary tumor cells cultured for 1-week under serum-free conditions grew as tumorspheres and were found to express PAC1 receptor transcripts. Gli1 gene expression was significantly reduced by SANT-1, PACAP and forskolin, but was unaffected by purmorphamine. The attenuation of gli1 gene expression by PACAP was reversed by the PKA inhibitor H89, which also blocked PKA activation. Treatment of tumorsphere cultures with PACAP, forskolin, and SANT-1 for 24 or 48 hours reduced proliferation. Primary tumorspheres derived from ptch1 +/- /p53 +/- mice exhibit constitutive HH pathway activity

  6. Gli archivi dell'Inquisizione in Italia: problemi storiografici e descrittivi. Roma, Archivio di Stato, 18 febbraio 2005

    Directory of Open Access Journals (Sweden)

    Andrea Del Col (editor

    2006-01-01

    Full Text Available It includes the folowing essays:Andrea Del Col, Presentazione Adriano Prosperi, Nuove prospettive per una storia dell'Inquisizione Grado Giovanni Merlo, Problemi documentari dell'Inquisizione medievale in Italia Silvana Seidel Menchi, I giudici dell'Inquisizione romana: inquisitori e vescovi, commissari, nunzi, cardinali, papi Andrea Del Col, I documenti del Sant'Ufficio come fonti per la storia istituzionale e la storia degli inquisiti Marco Pizzo, La Stanza Storica dell'Archivio del Sant'Uffizio: un metodo di intervento Francesca Cavazzana Romanelli, Il censimento della documentazione inquisitoriale riguardante l'Italia Giovanna Paolin - Andrea Del Col, La banca dati dei processi e la ricostruzione completa dell'attività del Sant'Ufficio di Aquileia e Concordia

  7. Gaimar, Wace e gli altri autori. La traduzione alle origini della letteratura anglo-normanna

    Directory of Open Access Journals (Sweden)

    Margherita Lecco

    2015-05-01

    Full Text Available L’articolo traccia un breve profilo del passaggio dall’impiego della lingua latina ed anglo-sassone presso le corti dei re Normanni d’Inghilterra alla lingua anglo-normanna per la stesura di opere dapprima storiche, poi propriamente letterarie. L’uso del volgare, che si avvia con Geffrei Gaimar intorno al 1140, viene mediato dalla traduzione dei testi che egli fa traendo la propria materia dalle opere degli storiografi attivi nel decennio precedente (Guillaume de Malmesbury e Geoffrey de Monmouth ma anche l’Anglo-Saxon Chronicle. Da latino a volgare, e da volgare (anglo-sassone e gallese a volgare, la letteratura anglo-normanna, attraverso l’incrocio e la traduzione da più lingue, viene definendo un corpus di tradizioni e di testi davvero cospicuo nell’età medievale europea. Dalla tradizione anglo-normanna, tuttavia, una letteratura ulteriore viene ad avviarsi, quella middle-english, che riprende l’english poco praticato in età normanna, pronto a risorgere come lingua non solo popolare ma anche letteraria, benché attraverso la ripresa, con un ulteriore processo di traduzione, di temi e testi anglo-normanni. This article briefly outlines the passage from the use of Latin and Anglo-Saxon to the Anglo-Norman language for writing first historical, then also literary works, at the court of the Norman kings of England. The vernacular was first used for literary creation by Geffrei Gaimar (around 1140, who took inspiration from and translated part of the Anglo-Saxon Chronicle and other works of historiographers active in the previous decade (Guillaume de Malmesbury and Geoffrey de Monmouth. The corpus of texts and traditions of Anglo-Norman literature – which is rather conspicuous when compared to others of medieval European literature – generated from intersections and translations of several languages: mainly Latin, Anglo-Saxon and Welsh. The Anglo-Norman literary tradition would, in its turn, pave the way for a new

  8. Il Discorso o Dialogo di Machiavelli: Per l’“Evento” del Materialismo

    Directory of Open Access Journals (Sweden)

    Yuri Brunello

    2014-12-01

    Full Text Available L’autenticità del Discorso o dialogo intorno alla nostra lingua è stata più volte messa in discussione. A tutti gli effetti, l’immagine di Machiavelli che affiora dal Discorso o dialogo rientra in una discorsività incompatibile con il cinismo assolutista o con l’utopismo patriottico e populista associato per secoli al nome di Machiavelli. L’emergere del materialismo del Discorso o dialogo, come anche del Principe, è stato il più delle volte rimosso da un’esegesi interessata a reprimerne il messaggio sovversivo. Richiamando Spinoza, Gramsci e Badiou, il presente lavoro si propone di analizzare il materialismo di Machiavelli e la sua portata rivoluzionaria

  9. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Science.gov (United States)

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

  10. Direct Assessment of the Effect of the Gly380Arg Achondroplasia Mutation on FGFR3 Dimerization Using Quantitative Imaging FRET

    Science.gov (United States)

    Placone, Jesse; Hristova, Kalina

    2012-01-01

    The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH), the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand. PMID:23056398

  11. Direct assessment of the effect of the Gly380Arg achondroplasia mutation on FGFR3 dimerization using quantitative imaging FRET.

    Directory of Open Access Journals (Sweden)

    Jesse Placone

    Full Text Available The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH, the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand.

  12. Microbial expression of proteins containing long repetitive Arg-Gly-Asp cell adhesive motifs created by overlap elongation PCR

    International Nuclear Information System (INIS)

    Kurihara, Hiroyuki; Shinkai, Masashige; Nagamune, Teruyuki

    2004-01-01

    We developed a novel method for creating repetitive DNA libraries using overlap elongation PCR, and prepared a DNA library encoding repetitive Arg-Gly-Asp (RGD) cell adhesive motifs. We obtained various length DNAs encoding repetitive RGD from a short monomer DNA (18 bp) after a thermal cyclic reaction without a DNA template for amplification, and isolated DNAs encoding 2, 21, and 43 repeats of the RGD motif. We cloned these DNAs into a protein expression vector and overexpressed them as thioredoxin fusion proteins: RGD2, RGD21, and RGD43, respectively. The solubility of RGD43 in water was low and it formed a fibrous precipitate in water. Scanning electron microscopy revealed that RGD43 formed a branched 3D-network structure in the solid state. To evaluate the function of the cell adhesive motifs in RGD43, mouse fibroblast cells were cultivated on the RGD43 scaffold. The fibroblast cells adhered to the RGD43 scaffold and extended long filopodia

  13. Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo.

    Science.gov (United States)

    Shevchenko, K V; Nagaev, I Yu; Babakov, V N; Andreeva, L A; Shevchenko, V P; Radilov, A S; Myasoedov, N F

    2015-01-01

    The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.

  14. Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients.

    Science.gov (United States)

    Krishnamoorthy, Soumya; Rajan, Roopa; Banerjee, Moinak; Kumar, Hardeep; Sarma, Gangadhara; Krishnan, Syam; Sarma, Sankara; Kishore, Asha

    2016-09-01

    Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson's disease (PD) patients. We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03-4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01-1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03-4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05-4.18, p = 0.035) were independently associated with ICD. DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype. Copyright © 2016. Published by Elsevier Ltd.

  15. The functional DRD3 Ser9Gly polymorphism (rs6280) is pleiotropic, affecting reward as well as movement.

    Science.gov (United States)

    Savitz, Jonathan; Hodgkinson, Colin A; Martin-Soelch, Chantal; Shen, Pei-Hong; Szczepanik, Joanna; Nugent, Allison; Herscovitch, Peter; Grace, Anthony A; Goldman, David; Drevets, Wayne C

    2013-01-01

    Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [(11)C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis.

  16. The functional DRD3 Ser9Gly polymorphism (rs6280 is pleiotropic, affecting reward as well as movement.

    Directory of Open Access Journals (Sweden)

    Jonathan Savitz

    Full Text Available Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3 gene (ser9gly, rs6280 on reward-associated dopamine (DA release in the striatum. Twenty-six healthy controls (HCs and 10 unmedicated subjects with major depressive disorder (MDD completed two positron emission tomography (PET scans with [(11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition and on another occasion subjects completed a gambling task (reward condition. A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release in the middle (anterior caudate (p<0.01 and the ventral striatum (p<0.05. The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis.

  17. Il comune di Cesena e gli Open Geo Data sugli incidenti stradali

    Directory of Open Access Journals (Sweden)

    Morena Moretti

    2015-02-01

    Full Text Available Il Comune di Cesena svolge dal 2005 una georeferenziazione degli incidenti stradali sui propri territori, raccog liendo una mole di dati che saranno pubblicati su un portale accessibile liberamente. Scopo del portale è informare i cittadini rispetto ai luog hi ad elevato tasso di incidentalità, alla trasparenza dell’ente rispetto agli interventi di sicurezza stradale e alle azioni di controllo nei period i critici.The Municipality of Cesena held since 2005, a georeferencing of road accidents of its territory. Since January 2015 these data will be published on the new open data portal of the City realized with technology StatPortal Open Data. By acting as "data visualization" these open geo data will be accessible via the web with maps, charts and graphs with multiple benefits, from increased knowledge of citizens compared to places with a high accident rate to the transparency of the institution from the measures road safety and control actions during critical periods. 

  18. LE PAROLE DELL’IDENTITA’: GLI ITALIANI VISTI DAI “NUOVI MILANESI”

    Directory of Open Access Journals (Sweden)

    Andrea Groppaldi

    2014-02-01

    Full Text Available La lingua dei “nuovi italiani” (in questo caso “nuovi milanesi” è lingua nuova, che si avvale di prestiti dalle lingue d’origine e li innesta in quella italiana. Ma è una lingua curiosa che si avvale anche di espressioni gergali, dialettismi, forme insolite e colorate che appartengono alla lingua non-ufficiale italiana. Esamina così un consistente numero di forme linguistiche tra italiano, dialetto, gerghi, prestiti e frasi idiomatiche, tratti in gran parte dagli autori che hanno partecipato al convegno. Nell’ultima parte del saggio prende in esame l’uso dei nomi e la loro funzione (talora di gabbia nel processo di integrazione delle varie etnìe.  Words of identity: italians viewed by the “new milanesi” The language of “new Italians” (in this case “new Milanesi” is a new language, which uses loans from the languages of origin and adds them to the Italian language. It is a curious language which also uses jargon, dialects, colorful and unusual forms that are part of the non-official Italian language. The paper examines a large number of linguistic forms between Italian, dialect, slang, idioms and loans, collected by the authors who participated in the conference. The last part examines the use of nouns and their function (sometimes like a cage in the integration process of the various ethnic groups.

  19. del alcoholismo

    Directory of Open Access Journals (Sweden)

    Rodrigo Arias Duque

    2005-01-01

    Full Text Available Desde el punto de vista farmacológico, es importante comprender qué es el alcohol y cómo actúa en el organismo. No existe una causa simple, sino una interacción complicada de factores neuroquímicos, fisiológicos, psicológicos y sociales que originan y desarrollan esta grave enfermedad fármaco-dependiente. La acción psicofisiológica y farmacodinámica del alcohol es fundamentalmente depresiva, por la reducción de la transmisión sináptica en el sistema nervioso humano. Es un hecho conocido que el consumo excesivo de alcohol causa una disfunción aguda y crónica del cerebro, produciendo trastornos en el sistema nervioso central, presentando alteraciones en la memoria y en las funciones intelectuales como cálculo, comprensión y aprendizaje. A nivel hepático tiene lugar, en su mayoría, el metabolismo del alcohol, produciéndose un hígado graso alcohólico, aumentando el tamaño, terminando en necrosis e inflamación grave del hígado; esto se llama hepatitis alcohólica, y si se sigue consumiendo alcohol se desarrollará la cirrosis. El alcohol también ha estado relacionado con alteraciones del miocardio; se ha constatado en animales de experimentación sanos que tanto la velocidad de contracción del músculo cardiaco y su máxima tensión disminuyen en presencia del alcohol, como consecuencia, la fuerza de cada contracción y el aumento de presión en el ventrículo izquierdo son menores, perdiendo eficacia el corazón como bomba.

  20. Juvenil hæmokromatose forårsaget af homozygot Gly320Val-mutation på hæmojuvelingenet

    DEFF Research Database (Denmark)

    Berg, Line Brunemark; Milman, Nils Thorm; Friis-Hansen, Lennart

    2013-01-01

    Juvenile haemochromatosis caused by a homozygous Gly320Val mutation in the haemojuvelin (HJV) gene was diagnosed in a 12-year-old Danish girl and her 10-year-old sister. Both appeared healthy without clinical or biochemical signs of organ damage. They had iron overload (plasma transferrin saturat...

  1. Immunity to endotoxin and Asp299Gly polymorphism of TLR-4 in adult patients with early and late onset of asthma

    Directory of Open Access Journals (Sweden)

    Yu. A. Bisyuk

    2015-06-01

    Full Text Available Aim. The gene polymorphism of Asp299Gly TLR-4 may be associated with the risk of asthma development. Methods and results. The gene polymorphism of TLR-4 (Asp299Gly receptor has been researched in 262 early-onset and in 69 late-onset asthma patients. The state of anti-endotoxin immunity was assessed by determination of specific antibodies to the endotoxin of A, M, G classes and sCD14 by ELISA. The polymorphism was analyzed by the allele-specific polymerase chain reaction with electrophoretic detection. It was estimated that the risk of early-onset asthma in the population of Crimea is associated with genotypes AG and GG (Asp299Gly of TLR-4. There were increased levels of anti-endotoxin IgM and decreased of sIgA in patients with late-onset asthma and AA genotype as compared to other genotypes. Conclusion. The gene polymorphism of Asp299Gly TLR-4 is associated with the risk of early-onset asthma development in Crimea population.

  2. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study

    International Nuclear Information System (INIS)

    Farmanzadeh, Davood; Ghazanfary, Samereh

    2014-01-01

    Graphical abstract: - Highlights: • Solvation energies show that the BNNTs/amino acids complex stabilizes in presence of solvent. • The adsorption process is sensitive to the external electric field. • The electric field is a suitable method for adsorption and storage of amino acids on BNNTs. - Abstract: The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF

  3. Association Analysis of Arg16Gly Polymorphism of the Beta2-adreneric Receptor Gene in Offspring from Hypertensive and Normotensive Families

    Czech Academy of Sciences Publication Activity Database

    Jindra, A.; Horký, K.; Peleška, Jan; Jáchymová, M.; Bultas, J.; Umnerová, V.; Heller, S.; Hlubocká, Z.

    2002-01-01

    Roč. 11, č. 4 (2002), s. 213-217 ISSN 0803-7051 R&D Projects: GA MZd NA5615 Keywords : Arg16Gly polymorphism of the beta2-adrenergic receptor gene * normotensive offspring * essential hypertension Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.344, year: 2002

  4. Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy.

    Science.gov (United States)

    Yan, Si; Guo, Changmiao; Hou, Guangjin; Zhang, Huilan; Lu, Xingyu; Williams, John Charles; Polenova, Tatyana

    2015-11-24

    Microtubules and their associated proteins perform a broad array of essential physiological functions, including mitosis, polarization and differentiation, cell migration, and vesicle and organelle transport. As such, they have been extensively studied at multiple levels of resolution (e.g., from structural biology to cell biology). Despite these efforts, there remain significant gaps in our knowledge concerning how microtubule-binding proteins bind to microtubules, how dynamics connect different conformational states, and how these interactions and dynamics affect cellular processes. Structures of microtubule-associated proteins assembled on polymeric microtubules are not known at atomic resolution. Here, we report a structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of dynactin motor on polymeric microtubules, solved by magic angle spinning NMR spectroscopy. We present the intermolecular interface of CAP-Gly with microtubules, derived by recording direct dipolar contacts between CAP-Gly and tubulin using double rotational echo double resonance (dREDOR)-filtered experiments. Our results indicate that the structure adopted by CAP-Gly varies, particularly around its loop regions, permitting its interaction with multiple binding partners and with the microtubules. To our knowledge, this study reports the first atomic-resolution structure of a microtubule-associated protein on polymeric microtubules. Our approach lays the foundation for atomic-resolution structural analysis of other microtubule-associated motors.

  5. The Tragedy of Migrants. Gabriele Del Grande's Reportage

    Directory of Open Access Journals (Sweden)

    Luigi Franchi

    2017-11-01

    Full Text Available L’espressione "Tragedia dei migranti" che ciclicamente compare nei notiziari televisivi, seppur evocando la categoria del tragico, non suscita nessuno dei sentimenti che caratterizzano questa forma di spettacolo. Lo spettatore infatti è portato a considerare i naufragi nel Mediterraneo il frutto di un destino ineluttabile, senza quindi intravedere alcuna possibilità da parte sua di intervenire sulla realtà. Mamadou va a morire e Il mare di mezzo di Gabriele Del Grande dimostrano come i naufragi dei migranti nel Mediterraneo non siano parte del disegno divino di un deus absconditus, ma una delle drammatiche conseguenze della crisi economica della contemporaneità. Esibendo i meccanismi sottesi al fenomeno della migrazione, l’autore mostra i presupposti razionali sui quali questa si fonda e suggerisce come i suoi esiti drammatici possano essere contrastati a livello individuale e collettivo. Questo articolo si propone di dotare di un senso più pieno l’espressione "tragedia dei migranti": per fare ciò si rintraccerà all’interno dei reportage la riemersione di alcuni topoi della tragedia greca. Verrà inoltre individuata tra gli individui incontrati da Del Grande nei suoi viaggi e i personaggi della tragedia greca una serie di analogie in grado di restituire alla condizione del migrante una reale potenzialità tragica.

  6. Culturas del Mundo

    DEFF Research Database (Denmark)

    Benwell, Ann Fenger; Costa, Alberto; Waehle, Espen

    2006-01-01

    ’Culturas del mundo. Colecciones del Museo Nacional de Dinamarca’ with Ann Fenger Benwell in Culturas del Mundo. Colecciones del Museo Nacional de Dinamarca, ed. Silvia Sauquet, Fundación "la Caixa", Barcelona 2006, pp. 31-39......’Culturas del mundo. Colecciones del Museo Nacional de Dinamarca’ with Ann Fenger Benwell in Culturas del Mundo. Colecciones del Museo Nacional de Dinamarca, ed. Silvia Sauquet, Fundación "la Caixa", Barcelona 2006, pp. 31-39...

  7. LUCI ED OMBRE NELL’ATTUAZIONE DEL SISTEMA DI RISOLUZIONE ALTERNATIVA DELLE CONTROVERSIE NEL CONTENZIOSO TRIBUTARIO ITALIANO ED IN QUELLO CROATO

    Directory of Open Access Journals (Sweden)

    Marco Greggi

    2017-01-01

    Full Text Available Nel lavoro gli autori esaminano il sistema della risoluzione alternativa delle controversie (ADR - Alternative Dispute Resolution nelle questioni fi scali in un’ottica comparatistica, ovvero alla luce delle legislazioni e delle dottrine italiana e croata. Nella prima parte del lavoro l’attenzione è rivolta all’esperienza italiana di attuazione del sistema ADR; mentre la seconda parte del lavoro è dedicata all’evoluzione del quadro normativo croato nei tentativi di costruzione di meccanismi di ADR. Il lavoro in entrambe le sue parti contiene una rassegna degli orientamenti dottrinali e attraverso i vari capitoli si sottolinea l’aspetto storico e teorico della questione esaminata. Gli autori dibattono ed espongono sul piano comparatistico anche le implicazioni dell’attuazione del sistema in esame; mentre l’infl uenza della dottrina di diritto pubblico sulla comparsa e lo sviluppo del sistema ADR viene evidenziata mediante l’esposizione della recente prassi italiana e croata del sistema di risoluzione dei contenziosi tributari.

  8. Book review. Anestesia e analgesia locoregionale del cane e del gatto. Francesco Staffieri

    Directory of Open Access Journals (Sweden)

    Manuel Graziani

    2014-03-01

    Full Text Available Il volume di anestesia e analgesia locoregionale del cane e del gatto è pensato per essere un testo "da sala operatoria" – come afferma l'autore – perché consente un rapido, ma allo stesso tempo dettagliato, consulto per il libero professionista che si trova a gestire un'anestesia. Si tratta di un piccolo libro, tascabile, che può essere considerato un punto di partenza per gli studenti e per tutti quei medici veterinari che intendono avvicinarsi in maniera specialistica all'arte dell'anestesiologia veterinaria. L'anestesia locoregionale costituisce, infatti, uno strumento insostituibile per la gestione del dolore perioperatorio in medicina veterinaria. Nel volume si forniscono le nozioni di base per praticare i principali blocchi nervosi centrali e periferici. Per ogni blocco sono riportate le tecniche alla cieca (mediante l'ausilio dei punti di repere anatomici e quelle con l'impiego dello stimolatore nervoso periferico. Il volume, corredato da immagini foto e grafici, per un totale di 65 figure, si apre con i capitoli relativi ai farmaci, agli strumenti e alle complicanze dell'anestesia locoregionale. Prosegue con i blocchi nervosi centrali (anestesia epidurale e spinale e si conclude con i blocchi periferici (testa, arto anteriore, torace, arto posteriore. L'autore, Francesco Staffieri, è un medico veterinario che svolge il dottorato di ricerca nel Dipartimento delle Emergenze e dei Trapianti di Organi, Sezioni di Cliniche Veterinarie e Produzioni Animali dell'Università degli Studi Aldo Moro di Bari.

  9. Meningo-encefalite equina da Halicephalobus gingivalis: contributo casistico nell’ambito delle attività di sorveglianza della Febbre del Nilo occidentale (West Nile disease

    Directory of Open Access Journals (Sweden)

    Gabriella Di Francesco

    2012-12-01

    Full Text Available Un cavallo di 7 anni è stato abbattuto dopo aver manifestato una grave sindrome neurologica a rapida evoluzione. Campioni tessutali sono stati inviati al Centro Studi Malattie Esotiche dell’Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale” (Istituto G. Caporale per gli accertamenti diagnostici del caso. Gli esami per le più comuni virosi neurologiche equine non hanno evidenziato la presenza di infezioni in atto. Istologicamente, si è osservata a livello encefalico la presenza di manicotti perivascolari e numerosi corpi parassitari, morfologicamente riferibili a Halicephalobus gingivalis. Il rinvenimento ha consentito di formulare la diagnosi di meningo-encefalite da H. gingivalis. Il caso riportato conferma che le encefaliti parassitarie devono essere annoverate nella diagnosi differenziale delle encefalopatie equine e sottolinea l’utilità dell’approccio diagnostico multidisciplinare.

  10. Structural requirements of acylated Gly-l-Ala-d-Glu analogs for activation of the innate immune receptor NOD2.

    Science.gov (United States)

    Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner; Jakopin, Žiga

    2016-06-30

    The fragment of bacterial peptidoglycan muramyl dipeptide (MDP) has long been known for its adjuvant activity, however the underlying mechanism of this action has only recently been elucidated. It is ascribed to its agonist action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In spite of the pressing need for novel adjuvants for human use, this discovery is hampered, by not knowing the structural requirements underlying the immunostimulatory activity. We have investigated how minor modifications of hit compound acyl Gly-L-Ala-D-Glu derivative I modulate the molecular recognition by NOD2. A series of novel desmuramyldipeptides has been designed and synthesized leading to the identification of compound 16, in which the sugar moiety is replaced by a 6-phenylindole moiety, that exhibits the strongest NOD2 activation to date sans the carbohydrate moiety. The results have enabled a deeper understanding of the structural requirements of desmuramylpeptides for NOD2 activation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo.

    Science.gov (United States)

    Reinhardt, Robert; Centanin, Lázaro; Tavhelidse, Tinatini; Inoue, Daigo; Wittbrodt, Beate; Concordet, Jean-Paul; Martinez-Morales, Juan Ramón; Wittbrodt, Joachim

    2015-06-03

    Transcriptional networks defining stemness in adult neural stem cells (NSCs) are largely unknown. We used the proximal cis-regulatory element (pCRE) of the retina-specific homeobox gene 2 (rx2) to address such a network. Lineage analysis in the fish retina identified rx2 as marker for multipotent NSCs. rx2-positive cells located in the peripheral ciliary marginal zone behave as stem cells for the neuroretina, or the retinal pigmented epithelium. We identified upstream regulators of rx2 interrogating the rx2 pCRE in a trans-regulation screen and focused on four TFs (Sox2, Tlx, Gli3, and Her9) activating or repressing rx2 expression. We demonstrated direct interaction of the rx2 pCRE with the four factors in vitro and in vivo. By conditional mosaic gain- and loss-of-function analyses, we validated the activity of those factors on regulating rx2 transcription and consequently modulating neuroretinal and RPE stem cell features. This becomes obvious by the rx2-mutant phenotypes that together with the data presented above identify rx2 as a transcriptional hub balancing stemness of neuroretinal and RPE stem cells in the adult fish retina. © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  12. HT_BIM: La modellazione parametrica per l’analisi del rischio nei centri storici

    Directory of Open Access Journals (Sweden)

    Assunta Pelliccio

    2017-06-01

    Full Text Available I centri storici minori sono dei monumenti d’ambiente da salvaguardare perché vulnerabili sia dal punto di vista sismico che ambientale. La gestione di queste realtà urbane è particolarmente complessa a causa dell’eterogeneità dei dati relativi alle singole unità edilizie, aggregati strutturali e intero ambito urbano. Negli ultimi anni i sistemi parametrici BIM hanno dato un enorme contributo alla progettazione, pianificazione, costruzione etc. di nuovi edifici e anche alla gestione del patrimonio culturale. L’obiettivo di questo lavoro è lo sviluppo del sistema Historical Town Building Information Modeling (HT_BIM, ovvero di un sistema BIM specifico per gli aggregati di edifici storici che, sulla base del rilievo, consente di individuare vulnerabilità legate sia ad aspetti strutturali sia a fenomeni di degrado da vento e soleggiamento.

  13. Giovanni Degli Alessandri: i primi anni del direttorato agli Uffizi fra nuovi e vecchi ruoli

    Directory of Open Access Journals (Sweden)

    Chiara Pasquinelli

    2011-11-01

    Full Text Available La figura di Giovanni Degli Alessandri (1765-1830, presidente dell’Accademia di Belle Arti di Firenze e direttore degli Uffizi tra gli anni napoleonici e la Restaurazione di Ferdinando III d’Asburgo-Lorena, è quella di un personaggio chiave nella politica artistica fiorentina, e toscana più in generale. Nel saggio si esaminano i primi anni del suo direttorato alla Galleria, i rapporti con Antonio Canova, il suo ruolo all’interno dell’entourage di Elisa Baciocchi Bonaparte, oltre a considerare alcuni spunti legati al rinnovamento degli Uffizi, nonché la delicata vicenda del passaggio in città di Dominique-Vivant Denon, direttore del Louvre. L’obbiettivo è quello di introdurre elementi di approfondimento relativamente a una figura molto nota ma poco studiata.

  14. «We have ceased to be a nation in retreat». Margaret Thatcher e gli usi strategici del conflitto

    Directory of Open Access Journals (Sweden)

    Lidia De Michelis

    2015-03-01

    Full Text Available This essay explores Margaret Thatcher’s political agency and leadership style in terms of her reliance on discursive and media strategies which thrived on the “confusion” of gender stereotypes and her ability to play with multiple, long-established archetypes of women in power, characterized by violent and aggressive femininity. Thatcher’s frequent self-projection as a “masculine” character, the “honorary man” of British politics, and her special grip on British public opinion and fantasies, were never disjointed from her ability to don, exploit, subvert and redirect “motherly’ (or at least “womanly” performances at will, in order to serve her political agenda. Focusing on her strategic deployment of a rhetoric and discourses of aggression, divisiveness, conflict and war, the essay highlights Thatcher’s ability to re-create and keep alive the idea of a national community always under siege, where extraordinary economic, disciplinary and defence measure were required in order to resist and overcome domestic and foreign “enemies”. The Falklands War will be taken as case study, for it provides an outstanding example of Thatcher’s powerful revision of female political authority against the backdrop of the conventionally masculine, heroic imaginary of war. Her masterly and coterminous performances as war leader and “super-mother” of the nation allowed for a complex and hybrid self-projection which still acts as an empowering model whose disciplinary subtext entails a nostalgic investment in imperial national history.

  15. Il clima dell'areale del Lago Maggiore durante gli ultimi cinquant'anni (The climate of Lago Maggiore area during the last fifty years)

    OpenAIRE

    Ambrosetti, Walter; Barbanti, Luigi; Rolla, Angelo

    2006-01-01

    Data collected in over 50 years' activity at the C.N.R. meteorological station of Pallanza were analysed to see whether any changes have taken place in some climatic elements and to quantify the extent of such changes. A statistical analysis of the respective historical series was performed on nine meteorological parameters (solar radiation, insolation, air temperature, atmospheric pressure, humidity, cloud cover, precipitation, evaporation and wind), and on two other strictly limnological fe...

  16. Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

    Science.gov (United States)

    Kamizato, Kota; Marsala, Silvia; Navarro, Michael; Kakinohana, Manabu; Platoshyn, Oleksandr; Yoshizumi, Tetsuya; Lukacova, Nadezda; Wancewicz, Ed; Powers, Berit; Mazur, Curt; Marsala, Martin

    2018-07-01

    The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Data on the purification and crystallization of the loss-of-function von Willebrand disease variant (p.Gly1324Ser of the von Willebrand factor A1 domain

    Directory of Open Access Journals (Sweden)

    James C. Cambell

    2016-06-01

    In this data article we describe the production, quality control and crystallization of the p.Gly1324Ser vWD variant of the A1 domain of VWF. p.Gly1324Ser A1 was expressed in Escherichia coli as insoluble inclusion bodies. After the preparation of the inclusion bodies, the protein was solubilized, refolded, purified by affinity chromatography and crystallized. The crystal structure of the p.Gly1324Ser mutant of the A1 domain is deposited at the Protein Data Bank PDB: 5BV8

  18. Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy.

    Science.gov (United States)

    Shigekiyo, Toshio; Sekimoto, Etsuko; Shibata, Hironobu; Ozaki, Shuji; Okumura, Takanobu; Fujinaga, Hiroyuki; Shibata, Hiroshi; Aihara, Ken-ichi; Akaike, Masashi

    2015-12-01

    An 81-year-old man was referred to our department because of suspected factor VII (FVII) deficiency. His FVII activity was under 1%, whereas the FVII activity levels of his son and granddaughter were 65 and 109%, respectively. The nucleotide at position 3886 of his FVII gene was homozygous for G. A single T to G substitution results in the replacement of wild-type Cys at residue 22 by Gly. His son was heterozygous for G and T at position 3886, whereas his granddaughter was homozygous for wild-type T. These results suggest that he was homozygous for FVII Cys22Gly. He underwent radiofrequency ablation (RFA) for hepatocellular carcinoma, receiving 20 μg/kg of recombinant FVIIa prior to RFA and 10 μg/kg of recombinant FVIIa twice after RFA. He showed no bleeding tendency; however, a myocardial infarction was diagnosed and percutaneous coronary intervention was performed.

  19. Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation

    DEFF Research Database (Denmark)

    Wang, Zhenxing; D'Annessa, Ilda; Tesauro, Cinzia

    2015-01-01

    –DNA covalent adduct. In this work the role of the Gly717 residue, located in a α-helix structure bridging the active site and the linker domain, has been investigated mutating it in Phe. The mutation gives rise to drug resistance in vivo as observed through a viability assay of yeast cells. In vitro activity...... assays show that the mutant is characterized by a fast religation rate, only partially reduced by the presence of the drug. Comparative molecular dynamics simulations of the native and mutant proteins indicate that the mutation of Gly717 affects the motion orientation of the linker domain, changing its...... interaction with the DNA substrate, likely affecting the strand rotation and religation rate. The mutation also causes a slight rearrangement of the active site and of the drug binding site, providing an additional explanation for the lowered effect of camptothecin toward the mutant....

  20. Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines

    DEFF Research Database (Denmark)

    Olesen, Uffe H; Bojesen, Sophie; Gehl, Julie

    2017-01-01

    Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin...... of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines. The impact of treatment on the regulation of Hedgehog pathway target genes (GLI1 and PTCH1), measured by real-time PCR, was compared between UWBCC1 and HaCaT. Varying cell line sensitivity profiles...... to the examined anticancer drugs were observed. Generally, 24-h drug exposure was sufficient to reduce cell viability. We found that 5-FU, MTX, and cisplatin significantly downregulated the expression of two genes controlled by the Hedgehog pathway (≤25-, 2.9-, and 12.5-fold, respectively, for GLI1 in UWBCC1...

  1. Furio Jesi, Irène Némirovsky e la macchina mitologica del sangue ebraico

    Directory of Open Access Journals (Sweden)

    Andrea Rondini

    2015-11-01

    Full Text Available A partire dagli studi di Furio Jesi sull’accusa del sangue rivolta nei secoli contro gli ebrei, l’articolo analizza alcuni romanzi della scrittrice francese Irène Némirovsky in riferimento al tema del sangue. In particolare viene preso in considerazione Il Signore delle anime nel quale sembrano emergere tutte le caratteristiche mitologiche e gli stereotipi antisemiti collegati all’accusa del sangue, dal vampirismo alla natura selvaggia dell’ebreo alla sua capacità/necessità di mimetizzarsi all’interno della società. Starting from Furio Jesi’s studies on blood accusation directed against Jews over the centuries, the article analyses some novels of French writer Irène Némirovsky in reference to the theme of blood. In particular the article takes into consideration Master of souls in which seem to emerge all the mythological features and the  anti-Semitic stereotypes related to blood accusation, from vampirism to the wild nature of the Jew to his ability/need to camouflage himself within society.

  2. Il ruolo del topografo ieri, oggi e domani

    Directory of Open Access Journals (Sweden)

    Bryn Fosburgh

    2012-04-01

    Full Text Available Bryn Fosburgh, vice presidente di Trimble e membro del comitato esecutivo della società, fornisce ai lettori di GEOmedia la sua visione del ruolo del topografo (e dunque del geometra, in Italia al giorno d’oggi.Come cambia il suo ruolo in questo contesto? Secondo Fosburgh il topografo è diventato un professionista della gestione, interpretazione, analisi e rappresentazione dei dati geospaziali; il suo nuovo ruolo dev’essere quello di guida per tutti gli utenti che hanno a che fare con questo tipo di dati. The Role of the Surveyor Yesterday, Today and TomorrowOver the past 50 years, advances in technology have increased the efficiency of the surveying profession, particularly in meas-urement  and  data  collection.  However,  the  new  technolo-gies—coupled with the decreasing population of professional surveyors worldwide—mandate that the surveyor’s role must and will change to managing, interpreting, analyzing and por-traying geomatics data. The surveyor must guide geospatial data consumers in a variety of related disciplines on how data is collected and used while maintaining a high level of data integrity.

  3. La prolusione di rocco e le dottrine del processo penale

    Directory of Open Access Journals (Sweden)

    Renzo Orlandi

    2015-03-01

    Full Text Available L’articolo analizza le conseguenze del pensiero giuridico di Arturo Rocco, dal 1910 nella dottrina di procedura penale, ossia, il metodo tecnico-giuridico (esegesi, sistematica e critica. La dogmatica di procedura pena- le inizia con la monografia di Giovanni Conso, nel 1955. L’insoddisfazione con il tecnicismo giuridico e con la mancanza di maturità scientifica si è manifestata con Carnelutti nel 1946 (Cerenterola, sottolineando le peculiarità strutturali del procedimento penale. In questa prospettiva, il testo sottolinea la conferenza di Franco Cordero nel 1964 (Lecce, così come le lezioni da James Goldschmidt. Inoltre, negli anni sessanta, divennero importanti diritti fondamentali, di fronte alla Costituzione democratica, con un nuovo orientamento dottrinale. Il diritto processuale penale è stato considerato come diritto costituzionale applicato. Si segnalano gli insegnamenti di Amodio, Amato, Chiavario, Ferrua, Grevi, Iluminati, Massa e Nobili. Successivamente, l’articolo mette in evidenza il CPP del 1988, l’internazionalizzazione dei sistemi giuridici, l’importanza del diritto comparato e dei diritti fondamentali. Si conclude con il nuovo ordine mondiale dei diplomi internazionali e tribunali sovranazionali, con nuove esigenze, oltre il tecnicismo giuridico.

  4. Teorie del tutto la ricerca della spiegazione ultima

    CERN Document Server

    Barrow, John D

    1992-01-01

    «Come, quando e perché l’universo ha avuto origine? Questi interrogativi di carattere fondamentale sono stati fuori moda per secoli: gli scienziati ne diffidavano, teologi e filosofi se ne erano stancati. Poi, d’improvviso, gli scienziati hanno cominciato a porseli con la massima serietà, e i teologi si sono trovati, scavalcati, a dover tenere dietro alle teorizzazioni matematiche della nuova generazione di scienziati... Oggi i fisici credono di essersi imbattuti in una chiave capace di guidarci al segreto matematico che sta al cuore dell’universo: una scoperta che punta verso una “teoria del tutto”, una sorta di quadro onnicomprensivo di tutte le leggi di natura dal quale deve derivare, in modo logicamente ineccepibile, l’inevitabilità di tutto ciò che ci circonda. Una volta in possesso di questa stele di Rosetta cosmica, potremmo leggere il libro della natura in tutta la sua estensione temporale, e intendere ogni cosa che sia stata, che è e che sarà. Di questa possibilità si è sempre fa...

  5. A Gly1127Ser mutation in an EGF-like domain of the Fibrillin-I gene is a risk factor for ascending aortic aneurysm and dissection

    Energy Technology Data Exchange (ETDEWEB)

    Francke, U.; Berg, M.A.; Tynan, K. [Stanford Univ. Medical Center, CA (United States)] [and others

    1995-06-01

    Ascending aortic disease, ranging from mild aortic root enlargement to aneurysm and/or dissection, has been identified in 10 individuals of a kindred, none of whom had classical Marfan syndrome (MFS). Single-strand conformation analysis of the entire fibrillin-1 (FBN1) cDNA of an affected family member revealed a G-to-A transition at nucleotide 3379, predicting a Gly1127Ser substitution. The glycine in this position is highly conserved in EGF-like domains of FBN1 and other proteins. This mutation was present in 9 of 10 affected family members and in 1 young unaffected member but was not found in other unaffected members, in 168 chromsomes from normal controls, and in 188 chromosomes from other individuals with MFS or related phenotypes. FBN1 intragenic marker haplotypes ruled out the possibility that the other allele played a significant role in modulating the phenotype in this family. Pulse-chase studies revealed normal fibrillin synthesis but reduced fibrillin deposition into the extracellular matrix in cultured fibroblasts from a Gly1127Ser carrier. We postulate that the Gly1127Ser FBN1 mutation is responsible for reduced matrix deposition. We suggest that mutations such as this one may disrupt EFG-like domain folding less drastically than do substitutions of cysteine or of other amino acids important for calcium-binding that cause classical MFS. The Gly 1127Ser mutation, therefore, produces a mild form of autosomal dominantly inherited weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection later in life. 33 refs., 6 figs.

  6. Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

    Directory of Open Access Journals (Sweden)

    Douglas Blackiston

    2011-01-01

    Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.

  7. Flexible xxx-asp/asn and gly-xxx residues of equine cytochrome C in matrix-assisted laser desorption/ionization in-source decay mass spectrometry.

    Science.gov (United States)

    Takayama, Mitsuo

    2012-01-01

    The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx-Asp/Asn and Gly-Xxx, were identified from the discontinuous intense peak of c'-ions originating from specific cleavage at N-Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c'-ions originating from N-Cα bond cleavage at Xxx-Asp/Asn and Gly-Xxx residues, but also C-terminal side complement z'-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX.

  8. Retrieval of precipitable water using near infrared channels of Global Imager/Advanced Earth Observing Satellite-II (GLI/ADEOS-II)

    International Nuclear Information System (INIS)

    Kuji, M.; Uchiyama, A.

    2002-01-01

    Retrieval of precipitable water (vertically integrated water vapor amount) is proposed using near infrared channels og Global Imager onboard Advanced Earth Observing Satellite-II (GLI/ADEOS-II). The principle of retrieval algorithm is based upon that adopted with Moderate Resolution Imaging Spectroradiometer (MODIS) onboard Earth Observing System (EOS) satellite series. Simulations were carried out with GLI Signal Simulator (GSS) to calculate the radiance ratio between water vapor absorbing bands and non-absorbing bands. As a result, it is found that for the case of high spectral reflectance background (a bright target) such as the land surface, the calibration curves are sensitive to the precipitable water variation. For the case of low albedo background (a dark target) such as the ocean surface, on the contrary, the calibration curve is not very sensitive to its variation under conditions of the large water vapor amount. It turns out that aerosol loading has little influence on the retrieval over a bright target for the aerosol optical thickness less than about 1.0 at 500nm. It is also anticipated that simultaneous retrieval of the water vapor amount using GLI data along with other channels will lead to improved accuracy of the determination of surface geophysical properties, such as vegetation, ocean color, and snow and ice, through the better atmospheric correction

  9. Dye adsorbates BrPDI, BrGly, and BrAsp on anatase TiO2(001) for dye-sensitized solar cell applications

    Science.gov (United States)

    Çakır, D.; Gülseren, O.; Mete, E.; Ellialtıoǧlu, Ş.

    2009-07-01

    Using the first-principles plane-wave pseudopotential method within density functional theory, we systematically investigated the interaction of perylenediimide (PDI)-based dye compounds (BrPDI, BrGly, and BrAsp) with both unreconstructed (UR) and reconstructed (RC) anatase TiO2(001) surfaces. All dye molecules form strong chemical bonds with surface in the most favorable adsorption structures. In UR-BrGly, RC-BrGly, and RC-BrAsp cases, we have observed that highest occupied molecular orbital and lowest unoccupied molecular orbital levels of molecules appear within band gap and conduction-band region, respectively. Moreover, we have obtained a gap narrowing upon adsorption of BrPDI on the RC surface. Because of the reduction in effective band gap of surface-dye system and possibly achieving the visible-light activity, these results are valuable for photovoltaic and photocatalytic applications. We have also considered the effects of hydration of surface to the binding of BrPDI. It has been found that the binding energy drops significantly for the completely hydrated surfaces.

  10. Alpha-adducin Gly460Trp polymorphism and hypertension risk: a meta-analysis of 22 studies including 14303 cases and 15961 controls.

    Directory of Open Access Journals (Sweden)

    Kuo Liu

    Full Text Available BACKGROUND: No clear consensus has been reached on the alpha-adducin polymorphism (Gly460Trp and essential hypertension risk. We performed a meta-analysis in an effort to systematically summarize the possible association. METHODOLOGY/PRINCIPAL FINDINGS: Studies were identified by searching MEDLINE and EMBASE databases complemented with perusal of bibliographies of retrieved articles and correspondence with original authors. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. We selected 22 studies that met the inclusion criteria including a total of 14303 hypertensive patients and 15961 normotensive controls. Overall, the 460Trp allele showed no statistically significant association with hypertension risk compared to Gly460 allele (P = 0.69, OR = 1.02, 95% CI 0.94-1.10, P(heterogeneity<0.0001 in all subjects. Meta-analysis under other genetic contrasts still did not reveal any significant association in all subjects, Caucasians, East Asians and others. The results were similar but heterogeneity did not persist when sensitivity analyses were limited to these studies. CONCLUSIONS/SIGNIFICANCE: Our meta-analysis failed to provide evidence for the genetic association of α-adducin gene Gly460Trp polymorphism with hypertension. Further studies investigating the effect of genetic networks, environmental factors, individual biological characteristics and their mutual interactions are needed to elucidate the possible mechanism for hypertension in humans.

  11. Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population.

    Science.gov (United States)

    Rey, G; Skowronek, F; Alciaturi, J; Alonso, J; Bertoni, B; Sapiro, R

    2008-09-01

    Preterm birth (PTB) is a worldwide health problem and remains the leading cause of perinatal morbidity and mortality. Systemic and local intrauterine infections have been implicated in the pathogenesis of preterm labor and delivery. Common pathways between PTB, premature rupture of ovular membranes (PROM) and altered molecular routes of inflammation have been proposed. There is evidence to support a genetic component in these conditions. Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is thought to play a key role in eliciting an inflammatory response. LPS is recognized by proteins of the innate immune system, including Toll-like receptor 4 (TLR4). Individuals from some European countries carrying the variant alleles resulting in an amino acid substitution (Asp299Gly) are at increased risk of Gram-negative infections and premature birth. The objective of this study was to determine if preterm newborns have different allele frequency of the Asp299Gly TLR4 variant from healthy term neonates in Uruguay. The impact of PROM was also examined. There was an increase in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being severely premature (<33 weeks) and to present PROM at the same time.

  12. Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

    Science.gov (United States)

    Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

    2009-08-19

    The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD

  13. Immunoproteomics based identification of thioredoxin reductase GliT and novel Aspergillus fumigatus antigens for serologic diagnosis of invasive aspergillosis.

    Science.gov (United States)

    Shi, Li-ning; Li, Fang-qiu; Huang, Mei; Lu, Jing-fen; Kong, Xiao-xiang; Wang, Shi-qin; Shao, Hai-feng

    2012-01-18

    There has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus. Extracellular proteins of A. fumigatus were separated by two-dimensional electrophoresis (2-DE) and probed with the sera from critically ill patients with proven IA. The immunoreactive protein spots were identified by MALDI-TOF mass spectrometry (MALDI-TOF -MS). Forty spots from 2DE gels were detected and 17 different proteins were identified as immunogenic in humans. Function annotation revealed that most of these proteins were metabolic enzymes involved in carbohydrate, fatty acid, amino acid, and energy metabolism. One of the proteins, thioredoxin reductase GliT (TR), which showed the best immunoactivity, was analyzed further for secretory signals, protein localization, and homology. The results indicated that TR is a secretory protein with a signal sequence exhibiting a high probability for secretion. Furthermore, TR did not match any human proteins, and had low homology with most other fungi. The recombinant TR was recognized by the sera of all proven IA patients with different underlying diseases in this study. The immunoreactive proteins identified in this study may be helpful for the diagnosis of IA in critically ill patients. Our results indicate that TR and other immunodominant antigens have potential as biomarkers for the serologic diagnosis of invasive aspergillosis.

  14. Immunoproteomics based identification of thioredoxin reductase GliT and novel Aspergillus fumigatus antigens for serologic diagnosis of invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Shi Li-ning

    2012-01-01

    Full Text Available Abstract Background There has been a rising incidence of invasive aspergillosis (IA in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus. Results Extracellular proteins of A. fumigatus were separated by two-dimensional electrophoresis (2-DE and probed with the sera from critically ill patients with proven IA. The immunoreactive protein spots were identified by MALDI-TOF mass spectrometry (MALDI-TOF -MS. Forty spots from 2DE gels were detected and 17 different proteins were identified as immunogenic in humans. Function annotation revealed that most of these proteins were metabolic enzymes involved in carbohydrate, fatty acid, amino acid, and energy metabolism. One of the proteins, thioredoxin reductase GliT (TR, which showed the best immunoactivity, was analyzed further for secretory signals, protein localization, and homology. The results indicated that TR is a secretory protein with a signal sequence exhibiting a high probability for secretion. Furthermore, TR did not match any human proteins, and had low homology with most other fungi. The recombinant TR was recognized by the sera of all proven IA patients with different underlying diseases in this study. Conclusions The immunoreactive proteins identified in this study may be helpful for the diagnosis of IA in critically ill patients. Our results indicate that TR and other immunodominant antigens have potential as biomarkers for the serologic diagnosis

  15. Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells.

    Science.gov (United States)

    Zhu, Wa-Wa; Wang, Shu-Rong; Liu, Zhi-Hua; Cao, Yong-Jun; Wang, Fen; Wang, Jing; Liu, Chun-Feng; Xie, Ying; Xie, Ying; Zhang, Yan-Lin

    2017-01-01

    Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif.

    Science.gov (United States)

    Rohrbeck, Astrid; Höltje, Markus; Adolf, Andrej; Oms, Elisabeth; Hagemann, Sandra; Ahnert-Hilger, Gudrun; Just, Ingo

    2017-10-27

    The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptake of C3 into cells still occurs (although reduced) in the absence of vimentin, indicating involvement of an additional host cell receptor. C3 harbors an Arg-Gly-Asp (RGD) motif, which is the major integrin-binding site, present in a variety of integrin ligands. To check whether the RGD motif of C3 is involved in binding to cells, we performed a competition assay with C3 and RGD peptide or with a monoclonal antibody binding to β1-integrin subunit and binding assays in different cell lines, primary neurons, and synaptosomes with C3-RGD mutants. Here, we report that preincubation of cells with the GRGDNP peptide strongly reduced C3 binding to cells. Moreover, mutation of the RGD motif reduced C3 binding to intact cells and also to recombinant vimentin. Anti-integrin antibodies also lowered the C3 binding to cells. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Il dono del racconto

    DEFF Research Database (Denmark)

    Polito, Paola

    1998-01-01

    L'articolo indaga a vari livelli strutturali del romanzo "Il coraggio del pettirosso" (rete metaforica, dialogismo diegetico, dialogismo come fenomeno di voce, strategie discorsive messe in atto dalla voce narrante, stile colloquiale) la complessa realizzazione testuale del genere narrativo...

  18. The sequential action of a dipeptidase and a beta-lyase is required for the release of the human body odorant 3-methyl-3-sulfanylhexan-1-ol from a secreted Cys-Gly-(S) conjugate by Corynebacteria.

    Science.gov (United States)

    Emter, Roger; Natsch, Andreas

    2008-07-25

    Human axillary odor is formed by the action of Corynebacteria on odorless axilla secretions. Sulfanylalkanols, 3-methyl-3-sulfanylhexan-1-ol in particular, form one key class of the odoriferous compounds. A conjugate with the dipeptide Cys-Gly has been reported as the secreted precursor for 3-methyl-3-sulfanylhexan-1-ol. Here, we confirm the Cys-Gly-(S) conjugate as the major precursor of this odorant, with lower levels of the Cys-(S) conjugate being present in axilla secretions. The enzymatic release of 3-methyl-3-sulfanylhexan-1-ol from the Cys-Gly-(S) conjugate by the axilla isolate Corynebacterium Ax20 was thus investigated. Cellular extracts of Ax20 released 3-methyl-3-sulfanylhexan-1-ol from the Cys-Gly-(S) conjugate and from the Cys-(S) conjugate, whereas the previously isolated C-S lyase of this bacterial strain was only able to cleave the Cys-(S) conjugate. o-Phenanthroline blocked the release from the Cys-Gly-(S) conjugate but did not affect cleavage of the Cys-(S) conjugate, indicating that in a first step, a metal-dependent dipeptidase hydrolyzes the Cys-Gly bond. This enzyme was purified by four chromatographic steps and gel electrophoresis, and the partial amino acid sequence was determined. The corresponding gene was cloned and expressed in Escherichia coli. It codes for a novel dipeptidase with a high affinity toward the Cys-Gly-(S) conjugate of 3-methyl-3-sulfanylhexan-1-ol. Co-incubating either the synthetic Cys-Gly-(S) conjugate or fresh axilla secretions with both the C-S lyase and the novel dipeptidase did release 3-methyl-3-sulfanylhexan-1-ol, proving that the sequential action of these two enzymes from the skin bacterium Corynebacterium Ax20 does release the odorant from the key secreted precursor.

  19. Water. Unresolved emergency of the Southern hemisphere; Acqua. Istanza irrisolta del Sud del mondo

    Energy Technology Data Exchange (ETDEWEB)

    Lotti, C. [Associazione Idrotecnica Italiana, Padua (Italy)

    2001-10-01

    Among the serious dramas in the Southern hemisphere, the most serious relates to health, and the most serious health problem is dysentery among the rural population, caused by the lack of unpolluted water. Bad management frustrates much of the aid sent to this part of the world, including projects to help the water crisis. In view of the success, it would appear that a concrete solution could be found within a decade, at a cost that can easily be sustained by the rich world, so long as funds are managed honestly. Much more ambitious and, at least for the moment, beyond all concrete possibility, is the project to provide a barrel of water per head to each person in the southern hemisphere. Providing unpolluted water and facilitating farming development through minor irrigation and family cattle-raising schemes is an idea that appears entirely Utopian. The conclusion provides a critical analysis of the major hydraulic works essential for true development, but effective only if the human environment is ready to receive them, whereas minor works are useful in any case - at village level - to resolve the thirst of the southern hemisphere. [Italian] Fra i gravi drammi del Sud del Mondo certamente il piu' grave e' quello sanitario; ed in quello sanitario la dissenteria causata dalla mancanza di acque non inquinate a gran parte della popolazione rurale. I molti aiuti destinati a questa parte del mondo sono stati vanificati dalla loro cattiva gestione: fra di essi gli interventi a favore dell'acqua. Da alcuni interventi ad esito positivo si puo' pervenire ad una soluzione concreta nel giro di un decennio. Molto piu' ambizioso ed -almeno per ora- fuori da ogni ipotesi concreta e' quello di rifornire di un barile di acqua pro capite ogni individuo del Sud del Mondo: per dare acqua non inquinata e favorire lo sviluppo alimentare attraverso piccole irrigazioni e familiari allevamenti di bestiame: cio' appare, comunque relegato allo scenario

  20. Gli Archetipi della Fantasia

    Directory of Open Access Journals (Sweden)

    Michela De Domenico

    2015-12-01

    Full Text Available In comics, visions of fantastic architecture contributed, along visions of utopia architecture in movies and video games, to the creation of an imaginary fantastic architecture. At the base of these creations there’s an ideational process starting from drawings and that allows to see things and locations not existing yet. In such – not fully explored – context, target is to investigate themes related to ephemeral and fantasy then set up tools for analysis through the research of main archetypes, the identification of the grammar and semiotic who communise message of such architectures. Target is to show, by the mutual exchages among cities and comics, the existence of a cross area inspired to a memory of common architecture, to a similar imaginary, and showing a common interest for ambient mutations.

  1. L’arte del paesaggio e la sua trasformazione

    Directory of Open Access Journals (Sweden)

    Raffaele Milani

    2015-11-01

    Full Text Available Leggere il paesaggio significa capire la natura, la storia e la cultura di un luogo. Una lettura importante per recuperare i segni del passato, renderli visibili e accostarli a più recenti segni provenienti dalle nuove richieste di possibili trasformazioni. Le forme riconoscibili di un paesaggio rivelano pagine di una lunga storia, dalla tradizione alla modernità. Perché esso è moderno e antico allo stesso tempo. Il paesaggio esprime un’immagine di forme, una reazione sentimentale e allo stesso tempo un’esigenza d’astrazione. E’ categoria dell’oggetto e del soggetto. Dufrenne, in un secolo che sembrava avesse dimenticato la bellezza del paesaggio, aveva elogiato sin dal 1955 la percezione estetica della natura sottolineando una certa indistinzione del sensoriale e dell’affettivo. In generale si accenna a un’arte del paesaggio quando esso viene concepito e sentito in relazione allo sguardo pittorico, alla veduta, alla teatralizzazione della natura, alle suggestioni visive delle note di viaggio. Ma, se vogliamo veramente pensarlo come un’arte dell’origine, un’arte che precede i suoi riflessi nella riproduzione dell’arte figurativa, esso ci appare più ampiamente e profondamente unito a un insieme di aspetti che mettono in luce l’uomo tra natura, cultura, storia e mito. Quest’ultimo si fa poi strumento importantissimo nel cogliere e trasmettere il mistero, l’inesplicabile, l’invisibile. Il paesaggio è, allora, sia reale, un’arte fornita dal fare e dalla cultura di un popolo, sia mentale, legato alla rappresentazione e alla visione del mondo. Gli architetti e i paesaggisti che sono invitati a ridare dignità a un territorio degradato, o troppo alterato e manipolato, dovranno ricordarsi dell’interazione di queste due accezioni ed essere capaci di leggere e interpretare i segni della presenza dell’uomo e migliorare così l’aspetto dei luoghi. 

  2. del cambio

    Directory of Open Access Journals (Sweden)

    Alejandro Canales

    2006-01-01

    Full Text Available El artículo analiza las propuestas y los compromisos en materia de cobertura y de financiamiento en el periodo 2000-2006. En particular, revisa las modificaciones y los ajustes de los tres principales documentos en los que se expresaron las iniciativas: el de la Asociación Nacional de Universidades e Instituciones de Educación Superior, el del equipo de la transición y el programa sectorial. Los resultados muestran que las cifras de atención a la demanda educativa e inversión quedaron lejos de las metas autoimpuestas por el gobierno federal y que será necesario realizar mayores esfuerzos para atender tales desafíos.

  3. [Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

    Science.gov (United States)

    Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

  4. La superaci??n del modelo del ??ngel del hogar:

    OpenAIRE

    Hurtado Mu??oz, M??nica

    2012-01-01

    La Tesis Doctoral titulada "La superaci??n del modelo del "??ngel del hogar". Recuperaci??n de la escritora Leonor Canalejas y Fustegueras (1869-1945)" aborda, en primer lugar, un an??lisis sociol??gico de las circunstancias que rodearon a la mujer espa??ola en el cambio de siglo en el ??mbito social y educativo, en un intento de esclarecer las caracter??sticas propias del contexto en el que la mujer accede a la intelectualidad en general y a la literatura en particular. Esta parte concluye q...

  5. Gly184 of the Escherichia coli cAMP receptor protein provides optimal context for both DNA binding and RNA polymerase interaction.

    Science.gov (United States)

    Hicks, Matt N; Gunasekara, Sanjiva; Serate, Jose; Park, Jin; Mosharaf, Pegah; Zhou, Yue; Lee, Jin-Won; Youn, Hwan

    2017-10-01

    The Escherichia coli cAMP receptor protein (CRP) utilizes the helix-turn-helix motif for DNA binding. The CRP's recognition helix, termed F-helix, includes a stretch of six amino acids (Arg180, Glu181, Thr182, Val183, Gly184, and Arg185) for direct DNA contacts. Arg180, Glu181 and Arg185 are known as important residues for DNA binding and specificity, but little has been studied for the other residues. Here we show that Gly184 is another F-helix residue critical for the transcriptional activation function of CRP. First, glycine was repeatedly selected at CRP position 184 for its unique ability to provide wild type-level transcriptional activation activity. To dissect the glycine requirement, wild type CRP and mutants G184A, G184F, G184S, and G184Y were purified and their in vitro DNA-binding activity was measured. G184A and G184F displayed reduced DNA binding, which may explain their low transcriptional activation activity. However, G184S and G184Y displayed apparently normal DNA affinity. Therefore, an additional factor is needed to account for the diminished transcriptional activation function in G184S and G184Y, and the best explanation is perturbations in their interaction with RNA polymerase. The fact that glycine is the smallest amino acid could not fully warrant its suitability, as shown in this study. We hypothesize that Gly184 fulfills the dual functions of DNA binding and RNA polymerase interaction by conferring conformational flexibility to the F-helix.

  6. Progressive Encephalomyelitis with Rigidity and Myoclonus Associated With Anti-GlyR Antibodies and Hodgkin’s Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Linda Borellini

    2017-08-01

    Full Text Available IntroductionA 60-year-old man presented with a 6-month history of low back pain and progressive rigidity of the trunk and lower limbs, followed by pruritus, dysphonia, hyperhydrosis, and urinary retention. Brain and spinal imaging were normal. EMG showed involuntary motor unit hyperactivity. Onconeural, antiglutamic acid decarboxylase (anti-GAD, voltage-gated potassium channel, and dipeptidyl peptidase-like protein 6 (DPPX autoantibodies were negative. CSF was negative. Symptoms were partially responsive to baclofen, gabapentin, and clonazepam, but he eventually developed severe dysphagia. Antiglycine receptor (anti-GlyR antibodies turned out positive on both serum and CSF. A plasmapheresis cycle was completed with good clinical response. A PET scan highlighted an isolated metabolically active axillary lymphnode that turned out to be a classic type Hodgkin lymphoma (HL, in the absence of bone marrow infiltration nor B symptoms. Polychemotherapy with ABVD protocol was completed with good clinical response and at 1-year follow-up the neurological examination is normal.BackgroundProgressive encephalomyelitis with rigidity and myoclonus (PERM is a rare and severe neurological syndrome characterized by muscular rigidity and spasms as well as brain stem and autonomic dysfunction. It can be associated with anti-GAD, GlyR, and DPPX antibodies. All of these autoantibodies may be variably associated with malignant tumors and their response to immunotherapy, as well as to tumor removal, is not easily predictable.ConclusionProgressive encephalomyelitis with rigidity and myoclonus has already been described in association with HL, but this is the first case report of a HL manifesting as anti-GlyR antibodies related PERM. Our report highlights the importance of malignancy screening in autoimmune syndromes of suspected paraneoplastic origin.

  7. Encapsulation of rat bone marrow stromal cells using a poly-ion complex gel of chitosan and succinylated poly(Pro-Hyp-Gly).

    Science.gov (United States)

    Kusumastuti, Yuni; Shibasaki, Yoshiaki; Hirohara, Shiho; Kobayashi, Mime; Terada, Kayo; Ando, Tsuyoshi; Tanihara, Masao

    2017-03-01

    Encapsulation of stem cells into a three-dimensional (3D) scaffold is necessary to achieve tissue regeneration. Prefabricated 3D scaffolds, such as fibres or porous sponges, have limitations regarding homogeneous cell distribution. Hydrogels that can encapsulate cells such as animal-derived collagen gels need adjustment of the pH and/or temperature upon cell mixing. In this report, we fabricated a poly-ion complex (PIC) hydrogel of chitosan and succinylated poly(Pro-Hyp-Gly) and assessed its effect on cell viability after encapsulation of rat bone marrow stromal cells. PIC hydrogels were obtained successfully with a concentration of each precursor as low as 3.0-3.8 mg/ml. The maximum gelation and swelling ratios were achieved with an equal molar ratio (1:1) of anionic and cationic groups. Using chitosan acetate as a cationic precursor produced a PIC hydrogel with both a significantly greater gelation ratio and a better swelling ratio than chitosan chloride. Ammonium succinylated poly(Pro-Hyp-Gly) as an anionic precursor gave similar gelation and swelling ratios to those of sodium succinylated poly(Pro-Hyp-Gly). Cell encapsulation was also achieved successfully by mixing rat bone marrow stromal cells with the PIC hydrogel simultaneously during its formation. The PIC hydrogel was maintained in the culture medium for 7 days at 37°C and the encapsulated cells survived and proliferated in it. Although it is necessary to improve its functionality, this PIC hydrogel has the potential to act as a 3D scaffold for cell encapsulation and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth

    Directory of Open Access Journals (Sweden)

    Jonathan M. Page

    2015-09-01

    Full Text Available The contents of this data in brief are related to the article titled “Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II”. In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2, poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP.

  9. ABC di corpi: alcuni alfabeti figurati del XVI secolo del Gabinetto Disegni e Stampe della Pinacoteca Nazionale di Bologna

    Directory of Open Access Journals (Sweden)

    Valeria Butera

    2013-10-01

    Full Text Available Fra le diverse tipologie di motivi ornamentali, gli alfabeti figurati costituiscono un vero e proprio genere a se stante, che attinge al repertorio iconografico del proprio tempo e lo riflette in composizioni dotate di grande fascino e originalità. Per la quantità, la qualità e l’eterogeneità degli esemplari custoditi, il Gabinetto Disegni e Stampe della Pinacoteca Nazionale di Bologna costituisce un caso più unico che raro in Italia, vantando alfabeti figurati che abbracciano ampi confini geografici e cronologici, spaziando dal tardo gotico al XIX secolo. Dopo una breve introduzione sulle vicende collezionistiche di un nucleo grafico così insolito e particolare, l’articolo si concentra su alcuni esemplari di alfabeti figurati del Cinquecento di area transalpina. Partendo dall’alfabeto dei bambini di Hans Weiditz (1521, costruito rispettando le più rigorose regole geometriche, codificate nei coevi trattati rinascimentali, ma anche riflesso del rinato gusto per i fregi all’antica con putti, si passa agli alfabeti di Peter Flötner (1534 e di Jost Amman (1567, dove le lettere sono integralmente costituite da corpi umani, forzati in complicate posture, talvolta persino licenziose. Questi esemplari rappresentano degli interessanti esperimenti calligrafici, dove l’uomo diviene concretamente l’unità di misura dei caratteri dell’alfabeto.

  10. Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Franco, Lucia; Yagaloff, Keith; Chen, Li

    2002-09-02

    A series of pentapeptides, based on Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and modified at the Arg(8) position, was prepared and pharmacologically characterized. Peptides containing either cyanoguanidine or acylguanidine, two substantially less basic arginine surrogates, were found to retain the agonist activity of the parent peptide at both hMC1R and hMC4R. This study unequivocally shows that the positive charge of Arg(8) is not essential for efficient interactions of our pentapeptide with both hMC1R and hMC4R.

  11. Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.

    Science.gov (United States)

    Li, Yangmei; Cazares, Margret; Wu, Jinhua; Houghten, Richard A; Toll, Laurence; Dooley, Colette

    2016-02-11

    To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

  12. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

    Science.gov (United States)

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

    2013-07-11

    FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

  13. Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

    DEFF Research Database (Denmark)

    Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart

    2007-01-01

    We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated...... a requirement for upstream domains for integrin-alpha(5)beta(1)-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding...

  14. A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma

    OpenAIRE

    Silva, Adriana Madeira Alvares da [UNIFESP; Maciel, Rui Monteiro de Barros [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Toledo, Silvia Regina Caminada de [UNIFESP; De Carvalho, Marcos B.; Cerutti, Janete Maria [UNIFESP

    2003-01-01

    Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13 - 15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cystein-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familia...

  15. Improving Tumor Uptake and Pharmacokinetics of 64Cu-Labeled Cyclic RGD Peptide Dimers with Gly3 and PEG4 Linkers

    OpenAIRE

    Shi, Jiyun; Kim, Young-Seung; Zhai, Shizhen; Liu, Zhaofei; Chen, Xiaoyuan; Liu, Shuang

    2009-01-01

    Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides represent a new class of radiotracers with potential for the early tumor detection and non-invasive monitoring of tumor metastasis and therapeutic response in cancer patients. This report describes the synthesis of two cyclic RGD peptide dimer conjugates, DOTA-PEG4-E[PEG4-c(RGDfK)]2 (DOTA-3PEG4-dimer: DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and DOTA-G3-E[G3-c(RGDfK)]2 ...

  16. Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease.

    Science.gov (United States)

    Odes, Shmuel; Friger, Michael; Vardi, Hillel; Claessens, Greet; Bossuyt, Xavier; Riis, Lene; Munkholm, Pia; Wolters, Frank; Yona, Hagit; Hoie, Ole; Beltrami, Marina; Tsianos, Epameinondas; Katsanos, Kostas; Mouzas, Ioannis; Clofent, Juan; Monteiro, Estela; Messori, Andrea; Politi, Patrizia; O'Morain, Colm; Limonard, Charles; Russel, Maurice; Vatn, Morten; Moum, Bjorn; Stockbrugger, Reinhold; Vermeire, Severine

    2007-07-01

    NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.

  17. Arminio nobile e la misura del cielo ovvero le disavventure di un astronomo napoletano

    CERN Document Server

    Capaccioli, Massimo

    2012-01-01

    La scienza è un’esaltante avventura che è costume raccontare attraverso le gesta dei grandi. Esiste però un’altra storia, altrettanto avvincente ma con poca voce, scritta dai tanti gregari e potenziali campioni cui la sorte, spesso nemmeno troppo cieca, ha negato la gloria. Questo libro parla di uno di loro e del suo piccolo mondo sulla collina di Capodimonte, a Napoli. È la parabola di Arminio Nobile – personaggio notevole eppure poco noto dell’astronomia italiana – svolta sulla scena della nascente astrofisica, in una stagione di grandi transizioni per il Mezzogiorno. Arminio, che era figlio di Giuseppina Guacci, figura di spicco della cultura pre-risorgimentale, e di un valente astronomo della Specola di Capodimonte, scelse di votarsi allo studio del cielo. Osservatore instancabile, appassionato e genialoide, aveva le carte in regola e le motivazioni per “sfondare”, ma la fortuna non gli arrise: più volte si beffò di lui, spingendolo su vicoli ciechi che la sua testardaggine gli impedì...

  18. Tritium labelling of highly selective probes for. delta. -opioid receptors: ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(O-t-Bu)(BUBU)

    Energy Technology Data Exchange (ETDEWEB)

    Fellion, E.; Gacel, G.; Roques, B.P. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France)); Roy, J.; Morgat, J.L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service de Biochimie)

    1990-08-01

    The introduction of bulky residue(s) in linear enkephalin-related hexapeptides represents a new approach in the design of selective probes for {delta}-opioid receptors, displaying the appropriate criteria to investigate biological and pharmacological properties of the assumed binding site ({delta}) of endogenous enkephalins. The selectivities and high affinities of Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and especially Tyr-D-Ser(O-t-Bu)Gly-Phe-Leu-Thr(O-t-Bu) (BUBU) associated with a satisfactory resistance to peptidases, make them the most suitable {delta}-probes reported to date. In the present paper, we report the synthesis of DSTBULET and BUBU under tritiated forms with high specific radioactivities. These radio-labelled probes will enable extensive in vitro and in vivo investigations of {delta}-opioid receptors properties to be carried out. (author).

  19. Fleeing War. Due strategie di diserzione letteraria:I parenti del Sud di Carlo Montella e Going After Cacciato di Tim O’Brien

    Directory of Open Access Journals (Sweden)

    Giulio Segato

    2014-10-01

    Full Text Available Il saggio indaga due diverse strategie di diserzione rappresentate in due romanzi di guerra: I parenti del sud di Carlo Montella e Going After Cacciato di Tim O’Brien. Nelle due opere analizzate la diserzione sembra essere collegata al conflitto che fa da sfondo al romanzo. Nel libro di Montella,il protagonista, ancora obnubilato dalle dottrine tautologiche fasciste, qualche settimana dopo l’armistizio di Cassibile decide di disertare e di fuggire nella villa di un’anziana parente, con lo scopo di rinsavire dall’ideologia del regime. Nel romanzo di O’Brien, invece, la fuga messa in scena dall’autore sembra avere gli stessi tratti grotteschi e assurdi del conflitto in cui è stato catapultato il protagonista,la Guerra del Vietnam.

  20. Thermo-chemotherapy Induced miR-218 upregulation inhibits the invasion of gastric cancer via targeting Gli2 and E-cadherin.

    Science.gov (United States)

    Ruan, Qiang; Fang, Zhi-Yuan; Cui, Shu-Zhong; Zhang, Xiang-Liang; Wu, Yin-Bing; Tang, Hong-Sheng; Tu, Yi-Nuo; Ding, Yan

    2015-08-01

    Thermo-chemotherapy has been proven to reduce the invasion capability of cancer cells. However, the molecular mechanism underlying this anti-invasion effect is still unclear. In this study, the role of thermo-chemotherapy in the inhibition of tumor invasion was studied. The results demonstrated that expression of miR-218 was downregulated in gastric cancer tissues, which had a positive correlation with tumor invasion and metastasis. In vitro thermo-chemotherapy increased miR-218 expression in SGC7901 cells and inhibited both proliferation and invasion of cancer cells. Gli2 was identified as a downstream target of miR-218, and its expression was negatively regulated by miR-218. The thermo-chemotherapy induced miR-218 upregulation was also accompanied by increasing of E-cadherin expression. In conclusion, the present study indicates that thermo-chemotherapy can effectively decrease the invasion capability of cancer cells and increase cell-cell adhesion. miR-218 and its downstream target Gli2, as well as E-cadherin, participate in the anti-invasion process.

  1. The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

    Directory of Open Access Journals (Sweden)

    Peter Steinbacher

    Full Text Available PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2. Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak. Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

  2. The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

    Science.gov (United States)

    Steinbacher, Peter; Feichtinger, René G; Kedenko, Lyudmyla; Kedenko, Igor; Reinhardt, Sandra; Schönauer, Anna-Lena; Leitner, Isabella; Sänger, Alexandra M; Stoiber, Walter; Kofler, Barbara; Förster, Holger; Paulweber, Bernhard; Ring-Dimitriou, Susanne

    2015-01-01

    PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

  3. Investigation of the spatial structure of des-Gly9-[Arg8]vasopressin by the methods of two-dimensional NMR spectroscopy and theoretical conformational analysis

    International Nuclear Information System (INIS)

    Shenderovich, M.D.; Sekatsis, I.P.; Liepin'sh, E.E.; Nikiforovich, G.V.; Papsuevich, O.S.

    1986-01-01

    An assignment of the 1 H NMR signals of des-Gly 9 -[Arg 8 ]vasopressin in dimethyl sulfoxide has been made by 2D spectroscopy. The SSCCs and temperature coefficients Δδ/Δ T have been obtained for the amide protons and the system of NOE cross-peaks in the two-dimensional NOESY spectrum has been analyzed. The most important information on the spatial structure of des-Gly 9 -[Arg 8 ]vasopressin is given by the low value of the temperature coefficient Δδ/Δ T of the Asn 5 amide proton and the NOE between the α-protons of Cys 1 and Cys 6 . It is assumed that the screening of the NH proton of the Asn 5 residue from the solvent is connected with a β-bend of the backbone in the 2-5 sequence, and the distance between the C/sup α/H atoms of the Cys 1 and Cys 6 residues does not exceed 4 A. Bearing these limitations in mind, a theoretical conformational analysis of the molecule has been made. The group of low-energy conformations of the backbone obtained has been compared with the complete set of NMR characteristics

  4. Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Bora-Singhal, Namrata; Perumal, Deepak; Nguyen, Jonathan; Chellappan, Srikumar

    2015-07-01

    Non-small cell lung cancer (NSCLC) patients have very low survival rates because the current therapeutic strategies are not fully effective. Although EGFR tyrosine kinase inhibitors are effective for NSCLC patients harboring EGFR mutations, patients invariably develop resistance to these agents. Alterations in multiple signaling cascades have been associated with the development of resistance to EGFR inhibitors. Sonic Hedgehog and associated Gli transcription factors play a major role in embryonic development and have recently been found to be reactivated in NSCLC, and elevated Gli1 levels correlate with poor prognosis. The Hedgehog pathway has been implicated in the functions of cancer stem cells, although the underlying molecular mechanisms are not clear. In this context, we demonstrate that Gli1 is a strong regulator of embryonic stem cell transcription factor Sox2. Depletion of Gli1 or inhibition of the Hedgehog signaling significantly abrogated the self-renewal of stem-like side-population cells from NSCLCs as well as vascular mimicry of such cells. Gli1 was found to transcriptionally regulate Sox2 through its promoter region, and Gli1 could be detected on the Sox2 promoter. Inhibition of Hedgehog signaling appeared to work cooperatively with EGFR inhibitors in markedly reducing the viability of NSCLC cells as well as the self-renewal of stem-like cells. Thus, our study demonstrates a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    Directory of Open Access Journals (Sweden)

    Eberhart Charles G

    2010-11-01

    Full Text Available Abstract Background The Sonic hedgehog (Shh signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63% and primary astrocytoma tumor samples (32%, but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.

  6. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    International Nuclear Information System (INIS)

    Shahi, Mehdi H; Afzal, Mohammad; Sinha, Subrata; Eberhart, Charles G; Rey, Juan A; Fan, Xing; Castresana, Javier S

    2010-01-01

    The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes

  7. Positive selection at codon 38 of the human KCNE1 (= minK gene and sporadic absence of 38Ser-coding mRNAs in Gly38Ser heterozygotes

    Directory of Open Access Journals (Sweden)

    Pfeufer Arne

    2009-08-01

    Full Text Available Abstract Background KCNE1 represents the regulatory beta-subunit of the slowly activating delayed rectifier potassium channel (IKs. Variants of KCNE1 have repeatedly been linked to the long-QT syndrome (LQTS, a disorder which predisposes to deafness, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Results We here analyze the evolution of the common Gly38Ser variant (rs1805127, using genomic DNAs, complementary DNAs, and HEK293-expressed variants of altogether 19 mammalian species. The between species comparison reveals that the human-specific Gly38Ser polymorphism evolved under strong positive Darwinian selection, probably in adaptation to specific challenges in the fine-tuning of IKs channels. The involved amino acid exchanges (Asp > Gly, Gly > Ser are moderately radical and do not induce apparent changes in posttranslational modification. According to population genetic analyses (HapMap phase II a heterozygote advantage accounts for the maintenance of the Gly38Ser polymorphism in humans. On the other hand, the expression of the 38Ser allele seems to be disadvantageous under certain conditions, as suggested by the sporadic deficiency of 38Ser-coding mRNAs in heterozygote Central Europeans and the depletion of homozygotes 38Ser in the Yoruban sample. Conclusion We speculate that individual differences in genomic imprinting or genomic recoding might have contributed to conflicting results of recent association studies between Gly38Ser polymorphism and QT phenotype. The findings thus highlight the relevance of mRNA data in future association studies of genotypes and clinical disorders. To the best of our knowledge, they moreover provide first time evidence for a unique pattern; i.e. coincidence of positive Darwinian selection and polymorphism with a sporadically suppressed expression of one allele.

  8. Acerca del moho

    Science.gov (United States)

    El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

  9. Del bit al qubit

    OpenAIRE

    Torras Font, Josep

    2011-01-01

    Aquest document pretén donar una visió del desenvolupament dels computadors electrònics i dels components que els han fet possibles. Dintre de les opcions de futur en computació, també intenta donar una visió de les bases en que es fonamenta la computació quàntica.

  10. Targeting a Cross-Reactive Gly m 5 Soy Peptide as Responsible for Hypersensitivity Reactions in a Milk Allergy Mouse Model

    Science.gov (United States)

    Curciarello, Renata; Smaldini, Paola L.; Candreva, Angela M.; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

    2014-01-01

    Background Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Methods Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

  11. Il portale del Servizio Geologico d’Italia

    Directory of Open Access Journals (Sweden)

    Loredana Battaglini

    2006-12-01

    Full Text Available Nell'ultimo decennio gli straordinari sforzi tecnologici hanno evoluto il settore geomatico e portato enormi vantaggi nell'ambito dei cosiddetti servizi a valore aggiunto. Tuttavia la svalutazione commerciale del sistema di navigazione satellitare ha fatto del navigatore un oggetto di uso comune, quasi alla pari del più quotato telefono cellulare. Scemata la corsa al cellulare più modaiolo è subentrata quella al navigatore satellitare più tecnologico con cartografia e punti di interesse più aggiornati. E' assai frequente trovare commercializzazioni degli operatori di telefonia che unisconoal dispositivo mobile il sistema di navigazione, grazie anche apolitiche di businness agreement tra le varie major. L'utilizzo dei dispositivi GPS è davvero ancora arenato alla semplice ricerca di un percorso o di un indirizzo da raggiungere? L'uso di tali apparecchiature può inserirsi all'interno di target quali l'intrattenimento e le attività ricreative? Negli ultimi anni stiamo riscoprendo la bellezza della natura e il piacere di dedicarci ad una serie di attività sportive outdoor che ci conciliano con essa, unendo ai benefici della mente quelli del corpo derivanti da una corretta sollecitazione della propria frequenza cardiaca. Questa mia relazione vuole essere un diario di viaggio nelle quotidiane attività all'aria aperta di un atleta non professionista, praticate durante le quattro stagioni sfruttando le tecnologie legate alla triangolazione satellitare.

  12. Dal mondo del pressappoco all'universo della precisione

    CERN Document Server

    Koyré, Alexandre

    1992-01-01

    I temi affrontati in questo libro da uno dei più autorevoli storici della scienza, Alexandre Koyré, sono oggetto di un vivace interesse da parte della nostra cultura. Koyré discute qui l'origine, la natura e la valutazione delle macchine e degli strumenti scientifici, considerati nei loro riflessi umani e sociali, più ancora che nelle loro caratteristiche tecniche. La sua analisi chiarisce i termini di alcune questioni fondamentali per la storia della tecnologia e della scienza, e del loro rapporto storico; perché ad esempio la scienza greca, scopritrice di fondamentali principi poi applicati trionfalmente dalla fisica moderna, non abbia cercato di tradurli in innovazioni tecniche; perché i notevolissimi ritrovati tecnici delle civiltà orientali e del Medioevo abbiano fallito a questo scopo; perché la rivoluzione scientifica dell'età moderna ci abbia dato col suo concetto dell'esperienza gli strumenti che sono alla base della civiltà industriale; quale sia infine il rapporto tra tecnica e scienza pu...

  13. Agenzia del Territorio, nuove argomentazioni su questioni classiche

    Directory of Open Access Journals (Sweden)

    Renzo Carlucci

    2011-04-01

    Full Text Available L’epocale rinnovamento del Catasto Italiano avviato negli anni ’80 ha visto un seconda fase nel momento in cui venne creata l’Agenzia del Territorio agli inizi di questo millennio portando a termine la digitalizzazione delle 300.000 mappe che coprono l’intero territorio italiano, gestendo dinamicamente un sistema di punti di riferimento oggi collegabili ai sistemi satellitari di posizionamento e integrando tutti gli archivi connessi al sistema della proprietà immobiliare e dei  valori distribuiti sul territorio. Sei temi sono stati oggetto di un colloquio con la Direzione dell’Agenzia.Italian Land Agency for Cadastre, new trends on classical issuesThe renovation of the Italian Cadastre started in the years '80s and a second stage ar-rived when a new Land Agency was created at the beginning of this millennium reach-ing goals as the completion of the vectorization of 300,000 maps covering the entire Italian territory, managing dynamically a system of reference points now connected to GPS network and integrating all the databases connected to the system of land owner-ship and values across the country. Six themes were the subject of an interview with the Management Agency Director.

  14. Agenzia del Territorio, nuove argomentazioni su questioni classiche

    Directory of Open Access Journals (Sweden)

    Renzo Carlucci

    2011-04-01

    Full Text Available L’epocale rinnovamento del Catasto Italiano avviato negli anni ’80 ha visto un seconda fase nel momento in cui venne creata l’Agenzia del Territorio agli inizi di questo millennio portando a termine la digitalizzazione delle 300.000 mappe che coprono l’intero territorio italiano, gestendo dinamicamente un sistema di punti di riferimento oggi collegabili ai sistemi satellitari di posizionamento e integrando tutti gli archivi connessi al sistema della proprietà immobiliare e dei  valori distribuiti sul territorio. Sei temi sono stati oggetto di un colloquio con la Direzione dell’Agenzia. Italian Land Agency for Cadastre, new trends on classical issues The renovation of the Italian Cadastre started in the years '80s and a second stage ar-rived when a new Land Agency was created at the beginning of this millennium reach-ing goals as the completion of the vectorization of 300,000 maps covering the entire Italian territory, managing dynamically a system of reference points now connected to GPS network and integrating all the databases connected to the system of land owner-ship and values across the country. Six themes were the subject of an interview with the Management Agency Director.

  15. La valle del Nilo: il paesaggio del mito nelle rappresentazioni cinematografiche / The Nile valley: the myth landscape in film representations

    Directory of Open Access Journals (Sweden)

    Claudio Gambino

    2016-05-01

    Full Text Available La valle del Nilo, per la pluralità delle sue vicende storico-culturali e per l’immagine di cui fruisce a livello planetario, si è manifestata nel tempo anche come suggestivo attrattore per la rappresentazione cinematografica, offrendo  meravigliosi scenari, sia dal punto di vista dell’ambiente naturale, sia dal punto divista dell’ambiente antropico. Questo grande fiume, così come lo chiamavano gli antichi egizi, ha fatto da cornice, tra gli altri, alla famosa opera filmica Assassinio sul Nilo, tratto dal più celebre dei romanzi di Agatha Christie. Un giallo ambientato a bordo dello Steam Ship Sudan, un battello fluviale che ancora oggi costituisce un must per tutti i turisti che prenotano una crociera sul Nilo. Nell’ambito di un progetto volto a promuovere il cineturismo ho ritenuto, perciò, opportuno proporre l’istituzione e l’attivazione di un Parco Cine-Letterario dedicato al romanzo-film della scrittrice britannica.   The Nile valley, with its plurality of its cultural and historical events and reputation worldwide, has become over the course of time an important attraction for film performances, offering spectacular scenarios, both from a natural and anthropic environment point of view. This Big River, named by ancient Egyptians, has provided the set for many films including Death on the Nile, based on the Agatha Christie mystery novel of the same name. It is a crime fiction that takes place aboard the Steam Ship Sudan, a fluvial steamship which is still a must for all the tourists who want to cruise the Nile. As a part of a project that intends to promote the movie-tourism, I believe it is appropriate to propose the institution and the activation of a Cine-Literary Park dedicated to the novel-film of the famous British writer.

  16. The increased incidence of the RET p.Gly691Ser variant in French-Canadian vesicoureteric reflux patients is not replicated by a larger study in Ireland.

    LENUS (Irish Health Repository)

    Darlow, John M

    2012-02-01

    The p.Gly691Ser variant of the RET protein, resulting from the \\'A\\' allele of the SNP rs1799939 in exon 11 of the RET gene, was recently found to be present in a high proportion of primary vesicoureteric reflux (pVUR) patients in Quebec. We have determined the genotype of this SNP in 221 unrelated index cases of pVUR from the Irish population, in 190 full siblings of 160 of the index cases, and in 592 healthy controls. We found no significant difference in genotype or allele frequencies in patients and controls, and no tendency of affected siblings to share the same genotype. We also found no difference in the presence of additional phenotypic features such as duplex kidneys, between patients with and without the \\'A\\' allele, and no difference in grade of reflux. We find no evidence of any influence of RET SNP rs1799939 on pVUR phenotype.

  17. Osteogenesis imperfecta Type IV: a newly identified variant at position c.560 (G > T; p.Gly187Val) in the COL1A2 gene.

    Science.gov (United States)

    Usta, Akin; Karademir, Dilay; Sen, Eylem; Yazici, Selcuk; Adali, Ertan; Erdem, Erkan; Karacan, Meric

    2017-01-01

    Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis of the newborn revealed a novel mutation at position c.560 (c.560 G > T) of the exon 12 in the COL1A2 gene; which lead to the glycine modification with valine (p.Gly187Val) at codon 187. The pregnancy follow-up was uneventful. After delivery, the newborn underwent biphosponat therapy and no fracture was detected until 1 year old.

  18. In-depth evaluation of Gly-Sar transport parameters as a function of culture time in the Caco-2 cell model

    DEFF Research Database (Denmark)

    Bravo, Silvina A.; Nielsen, Carsten Uhd; Amstrup, Jan

    2004-01-01

    The aim of the present study was to investigate the influence of culture time on hPEPT1-mediated transport in Caco-2 cell monolayers. Peptide transport activity in Caco-2 cells grown in standard media and in a "rapid" 4-day model was first compared. The rapid 4-day Caco-2 cell model, cultured using...... a cocktail of growth factors and agonists, displayed lower peptide uptake capacity than Caco-2 cells grown for 4 days in conventional media, and was judged to be unsuitable for peptide transport studies. Peptide transport activity as well as monolayer integrity and tissue morphology were evaluated...... in the standard >21 days model as a function of the culture time. Peptide transport activity was studied using [14C]-glycylsarcosine ([ 14C]-Gly-Sar). Monolayer integrity was evaluated by transepithelial electrical resistance (TEER) measurements and [3H]-mannitol permeabilities. Tissue morphology and hPEPT1...

  19. Synthesis of the tritium labelled β-casomorphine analogues 3H-Phe-Pro-Gly-OH and 3H2-Tyr-Pro-3H-Phe-pyrrolidide

    International Nuclear Information System (INIS)

    Oehlke, J.; Niedrich, H.; Born, I.; Neubert, K.; Mittag, E.

    1991-01-01

    The precursor peptides H-Phe(I)-Pro-Gly-OH (III) and H-Tyr(I 2 )-Pro-Phe(I)-pyrrolidide (VIII) were synthesized by stepwise elongation from the C-terminal end and by coupling of Boc-Tyr(I 2 )-Pro-OH with H-Phe(I)-pyrrolidide and following deprotection of the Boc-residue respectively. Catalytic dehalotritiation yielded tritated peptides with specific radioactivities of 450 and 1500 GBq/mmol respectively. Cleavage of 3 H 2 -Tyr-Pro- 3 H-Phe-pyrrolidide by dipeptidylpeptidase IV resulted in fragments with specific radioactivities of 950 ( 3 H 2 -Tyr-Pro) and 590 GBq/ mmol ( 3 H-Phe-pyrrolidide). (author)

  20. Role of Thr399Ile and Asp299Gly polymorphisms of toll-like receptor-4 gene in acute dental abscess.

    Science.gov (United States)

    Miri-Moghaddam, Ebrahim; Farhad-Mollashahi, Narges; Baghaee, Elnaz; Bazi, Ali; Garme, Yasaman

    2017-02-01

    Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls. Saliva sample containing mucosal epithelial cells was used for DNA extraction. Polymorphisms were detected by Tetra-ARMS (Amplification Refractory Mutation System) PCR method. Statistical analyses were carried out in SPSS 21 software. Homozygous wild type (CC) and heterozygous (CT) genotypes of Thr399Ile polymorphism were detected in 84% and 16% of AAA patients respectively. In controls, respective ratios were 94% (CC) and 6% (CT). Observed difference was not statistically significant ( P >0.05) for distribution of these genotypes. The mutant homozygous (TT) genotype of this polymorphism was identified in neither of the participants. Overall, T allele frequency was obtained 8% in AAA and 3% in AAP (OR=2.6, 95% CI; 0. 6-10.6, p >0.05). For Asp299Gly polymorphism, no individual was detected with the mutant allele in case or control groups. Our results indicated a possible role for Thr399Ile polymorphism in acute presentations of abscess in AAA. However, the impact of this polymorphism needs to be more assessed in future studies. Key words: Genetic polymorphism, periapical abscess, periapical periodontitis, toll-like receptor 4.

  1. Censura e doppiaggio nelle forme narrative del cinema italiano, nel cruciale passaggio al sonoro degli anni Trenta

    Directory of Open Access Journals (Sweden)

    Antonio Catolfi

    2015-10-01

    Full Text Available Il cinema italiano durante gli anni Venti conosce una profonda crisi determinata da vari fattori, tra cui il fallimento dell’Unione cinematografica italiana. I film muti prodotti in Italia passano dai 1029 del 1911 ai 415 del 1920. Sono solo 23 nel 1929. Nel 1930 si tocca il fondo con 18 film italiani e 374 stranieri. Dal 1932 al 1933 invece riprendono in modo lento a crescere: 1931 (27 italiani e 262 stranieri, 1932 (31 italiani e 229 stranieri, 1933 (36 italiani e 260 stranieri probabilmente grazie al cinema sonoro che inizia a diffondersi e ad altre concause. Dopo il successo negli Stati Uniti del film il Cantante di Jazz l’industria si converte rapidamente alla possibilità di rendere sonora la pellicola. In Italia il Cantante di Jazz arriva due anni dopo, il 19 aprile 1929. Appena nato il sonoro nel cinema, l’industria cinematografica italiana deve affrontare subito il problema delle barriere linguistiche che causava una difficoltà enorme per la commerciabilità dei prodotti italiani fuori dai confini nazionali. L’avvento del regime fascista non aiuta la situazione della crisi generale del cinema italiano perché nella sua prima fase il regime non si occupa del cinema in maniera diffusa.

  2. Impact of engineered Streptococcus thermophilus trains overexpressing glyA gene on folic acid and acetaldehyde production in fermented milk Impacto de linhagens de Streptococcus thermophilus com aumento da expressão do gene glyA na produção de ácido folico e acetaldeído em leite fermentado

    Directory of Open Access Journals (Sweden)

    Ana Carolina Sampaio Dória Chaves

    2003-11-01

    Full Text Available The typical yogurt flavor is caused by acetaldehyde produced through many different pathways by the yogurt starter bacteria L. bulgaricus and S. thermophilus. The attention was focused on one specific reaction for acetaldehyde and folic acid formation catalyzed by serine hydroxymethyltransferase (SHMT, encoded by the glyA gene. In S. thermophilus, this enzyme SHMT also plays the typical role of the enzyme threonine aldolase (TA that is the interconvertion of threonine into glycine and acetaldehyde. The behavior of engineered S. thermophilus strains in milk fermentation is described, folic acid and acetaldehyde production were measured and pH and counts were followed. The engineered S. thermophilus strains StA2305 and StB2305, have the glyA gene (encoding the enzyme serine hydroxymethyltransferase overexpressed. These engineered strains showed normal growth in milk when it was supplemented with Casitione. When they were used in milk fermentation it was observed an increase in folic acid and in acetaldehyde production by StA2305 and for StB2305 it was noticed a significative increase in folic acid formation.O acetaldeído, responsável pelo sabor e aroma característicos de iogurte, é produzido por diferentes vias metabólicas pelas bactérias lácticas: Streptococcus thermophilus (S. thermophilus e Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus. Neste trabalho, a atenção foi focada especificamente na reação para a formação de acetaldeído e de ácido fólico, catalisada pela enzima serina hidroximetil transferase (SHMT, codificada pelo gene glyA. A enzima SHMT catalisa diversas reações e, no caso da bactéria S. thermophilus, ela exerce também a atividade característica da enzima treonina aldolase (TA, definida como a interconversão do aminoácido treonina em glicina e acetaldeído. Foram construídas linhagens de S. thermophilus (StA2305 e StB2305 com super expressão do gene glyA. Estas linhagens modificadas apresentaram

  3. Algunas aclaraciones acerca del conocimiento del singular.

    Directory of Open Access Journals (Sweden)

    Carlos Llano Cifuentes

    2013-11-01

    Full Text Available Llano tries to explain the main purpose of El Conocimiento del Singular, showing how the individuals about which the book is concerned are basically human individuals: people as decision makers.

  4. Un progetto per l'attivazione di Agenda 21 Locale: monitoraggio della mammalofauna nell'area del Parco Regionale del Monte Cucco (Perugia

    Directory of Open Access Journals (Sweden)

    Roberta Mazzei

    2003-10-01

    Full Text Available Nell?ambito del progetto ?Attivazione Agenda 21 Locale? finalizzato alla realizzazione di studi per la certificazione e contabilizzazione ambientale, nel Parco Regionale del Monte Cucco, si è dato il via, a partire dal novembre del 2001, ad un?indagine di tipo qualitativo, mirata alla caratterizzazione dell?area Parco per quel che riguarda la presenza di specie di Mammiferi appenninici di interesse conservazionistico e naturalistico. Nel periodo che va dall?8 febbraio 2002 al 5 ottobre dello stesso anno, sono stati effettuati 16 transetti faunistici, distribuiti nell?arco delle quattro stagioni. Sono stati raccolti indici di presenza di 11 specie di Mammiferi appartenenti agli ordini degli Artiodattili, Carnivori, Lagomorfi, Insettivori e Roditori e i relativi IKA (indici chilometrici di abbondanza. I dati raccolti unitamente ad una ricognizione bibliografica, mirata a reperire informazioni pregresse e aggiornate sulla teriofauna locale, attraverso inoltre, l?effettuazione di interviste e il coinvolgimento della popolazione locale, hanno portato alla definizione di una Check-list della Mammalofauna del Parco, rappresentativa per il 56% di quella della Regione. La ricerca ha permesso di confermare per l?area la presenza del Lupo (Canis lupus e di evidenziare l?espansione a Sud del Capriolo (Capreolus capreolus. Parte integrante del progetto ?Cucco 21? era la definizione di proposte gestionali volte a migliorare il rapporto uomo-ambiente, laddove fossero state individuate situazioni di criticità oggettive o potenziali, in un?ottica di conservazione della risorsa naturale e di sviluppo delle attività antropiche. Significativi a tale proposito sono stati il caso del Cinghiale (Sus scrofa con l?osservazione del danno alle fitocenosi, soprattutto ai prati e pascoli cacuminali e del Capriolo. Per quest?ultima specie in funzione della sua espansione verso la parte meridionale del Parco, sono state avanzate delle

  5. Franco Modigliani e la teoria del ciclo vitale del consumo (Franco Modigliani and the life-cycle theory of consumption

    Directory of Open Access Journals (Sweden)

    Angus Deaton

    2012-04-01

    Full Text Available Nei primi anni ’50, Franco Modigliani e il suo studente Richard Brumberg elaborarono una teoria della spesa fondata sull’idea che gli individui effettuano scelte intelligenti su quanto desiderano spendere a ogni età, con il solo limite delle risorse disponibili nel corso della loro vita. Attraverso l’accumulo e il decumulo delle attività, chi lavora può provvedere alla propria pensione e, più in generale, può adattare i propri modelli di consumo alle esigenze che si presentano alle diverse età, indipendentemente dal reddito disponibile in ogni momento della sua vita. Questa semplice teoria conduce a previsioni rilevanti e non scontate per l’economia nel suo complesso, ad esempio che il risparmio nazionale dipende dal tasso di crescita del reddito nazionale e non dal suo livello, e che esiste una semplice relazione tra il livello della ricchezza nel sistema economico e la lunghezza del periodo trascorso in pensione. Tali previsioni, non verificabili negli anni ’50, hanno trovato considerevole sostegno empirico in successivi lavori di Modigliani e di altri ricercatori. Sebbene nel corso degli anni la teoria del consumo abbia subito numerosi attacchi, i più recenti dei quali mossi da una coalizione di psicologi ed economisti, l’ipotesi del ciclo vitale rimane una parte essenziale del pensiero degli economisti. Senza di essa avremmo molto meno da dire circa molte importanti questioni, quali l’offerta pubblica e privata di previdenza sociale, gli effetti del mercato azionario sull’economia, le conseguenze dei mutamenti demografici sul risparmio nazionale, il ruolo del risparmio nella crescita economica e le determinanti della ricchezza nazionale.  In the early '50s, Franco Modigliani and his student Richard Brumberg elaborated a theory of expenditure based on the idea that individuals make smart choices about how they want to spend at any age, with the only limit of the available resources in the course of

  6. Il SIT del Servizio Geologico d’Italia implementa i contenuti La banca dati dei sondaggi profondi per la ricerca di idrocarburi

    Directory of Open Access Journals (Sweden)

    Marco Pantaloni

    2007-04-01

    Full Text Available Il Servizio Geologico d’Italia - Dipartimento Difesa del Suolo, ha raccolto l’archivio storico dei pozzi per ricerca petrolifera perforati in Italia. Tale possibilità ci è stata consentita grazie alla cortese collaborazione dell’Ufficio Nazionale Minerario per gli Idrocarburi e la Geotermia (UNMIG della Direzione Generale dell’Energia e delle Risorse Minerarie (DGERM del Ministero dello Sviluppo Economico. Nell’archivio sono contenuti tutti i dati dell’attività di esplorazione e produzione degli idrocarburi in Italia depositati presso l’UNMIG dal 1957 a oggi, e che per legge possono essere resi pubblici dopo un anno dalla cessazione del titolo minerario della società che li ha realizzati.

  7. Effective Biotransformation of Ethyl 4-Chloro-3-Oxobutanoate into Ethyl (S)-4-Chloro-3-Hydroxybutanoate by Recombinant E. coli CCZU-T15 Whole Cells in [ChCl][Gly]-Water Media.

    Science.gov (United States)

    Dai, Yong; Huan, Bin; Zhang, Hai-Sheng; He, Yu-Cai

    2017-04-01

    To increase the biocatalytic activity of Escherichia coli CCZU-T15 whole cells, choline chloride/glycerol ([ChCl][Gly]) was firstly used as biocompatible solvent for the effective biotransformation of ethyl 4-chloro-3-oxobutanoate (COBE) into ethyl (S)-4-chloro-3-hydroxybutanoate [(S)-CHBE]. Furthermore, L-glutamine (150 mM) was added into [ChCl][Gly]-water ([ChCl][Gly] 12.5 vol%, pH 6.5) media instead of NAD + for increasing the biocatalytic efficiency. To further improve the biosynthesis of (S)-CHBE (>99 % e.e.) by E. coli CCZU-T15 whole cells, Tween-80 (7.5 mM) was also added into this reaction media, and (S)-CHBE (>9 % e.e.) could be effectively synthesized from 2000 and 3000 mM COBE in the yields of 100 and 93.0 % by whole cells of recombinant E. coli CCZU-T15, respectively. TEM image indicated that the cell membrane was permeabilized and lost its integrity and when the cell was exposed to [ChCl][Gly]-water media with Tween-80. Clearly, this bioprocess has high potential for the effective biosynthesis of (S)-CHBE (>99 % e.e.).

  8. Mutation of Gly195 of the ChlH subunit of Mg-chelatase reduces chlorophyll and further disrupts PS II assembly in a Ycf48-deficient strain of Synechocystis sp. PCC 6803

    Directory of Open Access Journals (Sweden)

    Tim Crawford

    2016-07-01

    Full Text Available Biogenesis of the photosystems in oxygenic phototrophs requires co-translational insertion of chlorophyll a. The first committed step of chlorophyll a biosynthesis is the insertion of a Mg2+ ion into the tetrapyrrole intermediate protoporphyrin IX, catalyzed by Mg-chelatase. We have identified a Synechocystis sp. PCC 6803 strain with a spontaneous mutation in chlH that results in a Gly195 to Glu substitution in a conserved region of the catalytic subunit of Mg-chelatase. Mutant strains containing the ChlH Gly195 to Glu mutation were generated using a two-step protocol that introduced the chlH gene into a putative neutral site in the chromosome prior to deletion of the native gene. The Gly195 to Glu mutation resulted in strains with decreased chlorophyll a. Deletion of the PS II assembly factor Ycf48 in a strain carrying the ChlH Gly195 to Glu mutation did not grow photoautotrophically. In addition, the ChlH-G195E:ΔYcf48 strain showed impaired PS II activity and decreased assembly of PS II centers in comparison to a ΔYcf48 strain. We suggest decreased chlorophyll in the ChlH-G195E mutant provides a background to screen for the role of assembly factors that are not essential under optimal growth conditions.

  9. Influence of turn (or fold) and local charge in fragmentation of the peptide analogue molecule CH3CO-Gly-NH2 following single-photon VUV (118.22 nm) ionization.

    Science.gov (United States)

    Bhattacharya, Atanu; Bernstein, Elliot R

    2011-10-06

    The radical cationic reactivity of the peptide analogue molecule CH(3)CO-Gly-NH(2) is addressed both experimentally and theoretically. The radical cation intermediate of CH(3)CO-Gly-NH(2) is created by single-photon ionization of this molecule at 118.22 nm (~10.5 eV). The two most stable conformers (C(7) and C(5)) of this molecule exhibit different folds along the backbone: the C(7) conformer has a γ-turn structure, and the C(5) conformer has a β-strand structure. The experimental results show that the radical cation intermediate of CH(3)CO-Gly-NH(2) dissociates and generates a fragment-ion signal at 73 amu that is observed through TOFMS. Theoretical results show how the fragment-ion signal at 73 amu is generated by only one conformer of CH(3)CO-Gly-NH(2) (C(7)) and how local charge and specific hydrogen bonding in the molecule influence fragmentation of the radical cation intermediate of CH(3)CO-Gly-NH(2). The specific fold of the molecule controls fragmentation of this reactive radical cation intermediate. Whereas the radical cation of the C(7) conformer dissociates through a hydrogen-transfer mechanism followed by HNCO elimination, the radical cation of the C(5) conformer does not dissociate at all. CASSCF calculations show that positive charge in the radical cationic C(7) conformer is localized at the NH(2)CO moiety of the molecular ion. This site-specific localization of the positive charge enhances the acidity of the terminal NH(2) group, facilitating hydrogen transfer from the NH(2) to the COCH(3) end of the molecular ion. Positive charge in the C(5) conformer of the CH(3)CO-Gly-NH(2) radical cation is, however, localized at the COCH(3) end of the molecular ion, and this conformer does not have enough energy to surmount the energy barrier to dissociation on the ion potential energy surface. CASSCF results show that conformation-specific localization of charge in the CH(3)CO-Gly-NH(2) molecular ion occurs as a result of the different hydrogen

  10. L'informazione per l'efficienza e la trasparenza del mercato immobiliare: l'esperienza italiana

    Directory of Open Access Journals (Sweden)

    Gianni Guerrieri

    2011-12-01

    Full Text Available Il tema affrontato concerne il ruolo dell’informazione economica nell’ambito dei mercati immobiliari. Si parte dai riferimenti della letteratura economica sulla teoria dell’informazione per individuare le informazioni economiche rilevanti per monitorare e analizzare il mercato immobiliare, sia dal punto di vista macroeconomico sia da quello microeconomico. In entrambi gli ambiti non è sufficiente soltanto l’informazione sul prezzo, ma su numerose altre variabili. Sull’importanza dell’informazione economica è utile l’indicatore della trasparenza dei mercati immobiliari elaborato da Jones Lang Lasalle costruito anche sulla base di una valutazione sulla qualità e quantità di informazione economica disponibile sugli oggetti scambiati sui fenomeni che caratterizzano il mercato immobiliare. Si analizza infine lo stato dell’informazione in Italia sul mercato immobiliare ed il ruolo e l’offerta informativa istituzionale resa dall’Osservatorio del mercato immobiliare dell’Agenzia del Territorio.

  11. Il senso del lavoro e il suo contesto. Una rilettura di Bartleby lo scrivano di Herman Melville

    Directory of Open Access Journals (Sweden)

    Giuseppe Ruvolo

    2015-09-01

    Full Text Available Attraverso una rilettura critica del noto racconto di Herman Melville Bartleby lo scrivano, viene proposta una chiave di comprensione psico-antropologica delle condotte lavorative, delle relazioni nei contesti lavorativi e delle loro ricadute psicopatologiche. In particolare viene avanzata una lettura che connette i comportamenti e le relazioni lavorative quali esiti della difficoltà dei singoli nella mentalizzazione dei modelli ideologico-culturali che li determinano in un dato momento storico. Viene criticata una lettura, tendenzialmente presente in psicologia clinica e in psicologia del lavoro, in chiave riduttivamente individualistica, la quale attribuisce al singolo presunti deficit psichici ricercando le cause, e gli antecedenti delle condotte disadattive delle formazioni psicopatologiche, nella sola storia personale e individuale dei soggetti.

  12. The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

    Science.gov (United States)

    Dorobek, Małgorzata; Ryniewicz, Barbara; Kabzińska, Dagmara; Fidziańska, Anna; Styczyńska, Maria; Hausmanowa-Petrusewicz, Irena

    2015-11-01

    Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A. Prevalence of this mutation in the Polish population has not been previously investigated. The aim of this study was to identify and estimate the frequency of the c.550delA mutation in Polish LGMD2A patients. Polymerase chain reaction-sequencing analysis, restriction fragment length polymorphism polymerase chain reaction method. We analyzed 76 families affected with LGMD and identified 62 probands with mutations in the CANP3 gene. C.550delA was the most common mutation identified, being found in 78% of the LGMD2A families. The remaining mutations observed multiple times were as follows: c.598-612del15ntd; c.2242C>T; c.418dupC; c.1356insT, listed in terms of decreasing frequency. Two novel variants in the CANP3 gene, that is, c.700G>A Gly234Arg and c.661G>A Gly221Ser were also characterized. Overall, mutations in the LGMD2A gene were estimated to be present in 81% of patients with the LGMD phenotype who were without sarcoglycans and dysferlin deficiency on immunocytochemical analysis. The frequency of the heterozygous c.550delA mutation in the healthy Polish population was estimated at 1/124. The c.550delA is the most frequent CANP3 mutation in the Polish population, thus sequencing of exon 4 of this gene could identify the majority of LGMD2A patients in Poland.

  13. Infrastrutture e pianificazione paesaggistica nel rinnovato Codice dei Beni culturali e del Paesaggio

    Directory of Open Access Journals (Sweden)

    Saverio Santangelo

    2012-08-01

    Full Text Available Le infrastrutture agiscono sul paesaggio con effetti sia diretti, e spazialmente limitati, che indiretti, e non precisamente limitati nello spazio e nel tempo. Gli effetti indiretti, in particolare, riguardano anche le infrastrutture che non vediamo, perché nel sottosuolo, o di cui vediamo solo gli elementi puntuali e materiali di reti prevalentemente immateriali. In quest’ultimo caso si tratta dei sistemi di flusso delle informazioni, che oggi e ancor più in prospettiva, insieme ai sistemi per la produzione locale di energia (segnatamente fotovoltaico ed eolico, rafforzano le tendenze all’indifferenza dei fattori localizzativi di attività e residenze. Tutto questo da un lato consente riduzioni dei suoli impegnati e, per alcuni versi, la stessa salvaguardia del paesaggio (possono ridursi le reti fisiche per il trasporto di energia elettrica e gas, ed esempio, ma dall’altro favorisce nuove domande di suolo a fini urbanizzativi e di infrastrutture, non soltanto stradali, per servire ed accedere alle nuove aree interessate dalla domanda, e quindi comporta altri impatti sul paesaggio.

  14. Psicodrama del duelo.

    OpenAIRE

    José Antonio Espina Barrio; Marisol Filgueira Bouza

    1997-01-01

    La pérdida de rituales agrava y alarga la reacción del duelo. Se define el Psicodrama Antropológico y su intervención en el proceso del duelo. El Psicodrama Focal del Duelo es una psicoterapia breve centrada en el proceso de Duelo. Se comentan varios casos y resultados. Se concluye con un programa sencillo para el duelo en Atención Primaria.

  15. Rapporto impegni/depositi ed incidenza del massimale di crescita. (The effect of growth limits on the loan/deposit ratio

    Directory of Open Access Journals (Sweden)

    A. NICCOLI

    2013-12-01

    Full Text Available Una breve nota sulla Marullo Reedtz ' Gli effetti di "limiti di crescita " sul sistema bancario e sulla distribuzione del credito , in cui l'autore chiarisce alcuni punti di disaccordo che esistono a livello teorico e cita alcune evidenze empiriche a loro sostegno .A brief note on Marullo Reedtz’ The effects of “growth limits” on the banking system and on the distribution of credit, in which the author clarifies some points of disagreement that exist at the theoretical level and cites some empirical evidence to support them.JEL: E51, E52, G21

  16. Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

    Science.gov (United States)

    Aradillas-Garc X Cd, Celia; Cruz, Miguel; Pérez-Luque, Elva; Garay-Sevilla, María E; Malacara, Juan M; R, Aduna; Peralta, Jesús; Burguete-García, Ana; Alegría-Torres, Jorge A

    2016-10-17

    This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c 2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c 2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

  17. Fractura triple del complejo suspensorio del hombro

    Directory of Open Access Journals (Sweden)

    Eraclio Delgado Rifá

    2015-06-01

    Full Text Available El complejo suspensorio del hombro es una estructura sumamente importante, compuesta por un anillo de huesos y tejidos blandos. Las lesiones aisladas de este complejo anatómico son frecuentes y no afectan su estabilidad. La interrupción doble conduce a la inestabilidad de esta estructura y usualmente requiere tratamiento quirúrgico. La triple interrupción, por su parte, es sumamente rara y es encontrada en casos de trauma de alta energía a menudo en asociación con otras lesiones. Se presenta una triple lesión del complejo suspensorio del hombro en un paciente de 46 años de edad, con una fractura de la glenoides, del acromion tipo III de Kuhn y de la coracoides tipo II de Ogawa. En este caso, la fractura del acromion fue tratada con fijación percutánea con alambres de Kirschner, por tener asociado lesiones de partes blandas que contraindicaron la reducción abierta. La fractura de la glenoides y de la apófisis coracoides fueron tratadas conservadoramente. Después de 6 meses de evolución, el paciente tuvo un resultado funcional aceptable, con una abducción de 90 grados, los 30 grados de rotación externa y 70 de rotación interna, además asintomático y consolidación de todas las fracturas. A pesar de ser catalogada de una lesión grave del cinturón escapular y estar asociada a otras lesiones se obtuvo un resultado satisfactorio al final del tratamiento.

  18. Una «tragedia in forma di romanzo»? Teatralità e intertestualità pirandelliana ne Gli indifferenti di Alberto Moravia / A «tragedia in forma di romanzo» (tragedy in the form of a novel? Theatricality and Pirandello’s inrtextuality in “Gli Indifferenti” by Alberto Moravia.

    Directory of Open Access Journals (Sweden)

    Agnese Marasca

    2015-06-01

    Gli indifferenti by Moravia is a theatrical novel both in the form for the use of techniques and procedures typical of drama, and in the content for the presence of subjects and figures which refer to the theater. The dimension of theatrics in the novel is also closely related to the intertextuality with Pirandello, from whom philosophical imaginary the romance takes a lot of suggestions, as first the mask and the staging social. But what deeply connects Gli indifferenti with the work of Pirandello is the theme of the impossibility of the tragedy, that is the first cause of Michele’s ineptitude in life. The loss of the tragic sense prevents the realization of the oedipal drama, because the tragic of the novel remains a purely external fact. The absence of any tragical assumption is clarified thanks to the comparison of the plot and the characters with the ones of Sei personaggi in cerca d’autore, with which Moravia’s novel has dense and hidden relations of intertextuality.

  19. Vigencia del Darwinismo

    OpenAIRE

    Lessa, Enrique P

    2009-01-01

    En este ensayo se presenta una revisión histórica del signifcado y legado del darwinismo, con énfasis en el último siglo. La principal conclusión es que la visión darwiniana de la evolución, con las modifcaciones requeridas para dar cuenta de los grandes desarrollos de la disciplina, se ha impuesto y mantiene vigencia en nuestros días. En particular, el papel del azar, la evolución como proceso de “descendencia con modifcación” a lo largo de diversas ramas del árbol de la vida, el pensamiento...

  20. L’indisponibilità del diritto all’integrità fisica della persona umana in ambito sportivo e i limiti al rischio consentito

    Directory of Open Access Journals (Sweden)

    Maria Cimmino

    2016-05-01

    Full Text Available Lo sport, espressione di valori come la lealtà e la correttezza, il rispetto delle regole, l’integrazione, la democrazia, è una forma di manifestazione della personalità umana, finalizzata, anche attraverso il tempo libero, al miglioramento del benessere psicofisico del singolo e della collettività. Tuttavia e paradossalmente talvolta esso può risolversi nell’uso della violenza e/o in un contrasto fisico tra gli atleti, contemplato in alcuni casi dai regolamenti sportivi. Come si giunge a valutare meritevoli le attività sportive nel quadro dei diritti fondamentali della persona costituzionalmente garantiti? Il lavoro si propone di analizzare i rapporti tra diritto allo sport e diritto all’integrità fisica attraverso una rilettura della teoria giurisprudenziale del rischio consentito, giungendo alla conclusione che nel bilanciamento di interessi di pari rango costituzionale, l’organizzatore di competizioni sportive rivesta una fondamentale posizione di garanzia e che occorre modulare l’applicazione della clausola del rischio consentito in ragione delle circostanze del caso concreto e della qualità del soggetto e del carattere amatoriale od agonistico dell’attività.

  1. La luz del origen del universo

    Directory of Open Access Journals (Sweden)

    Casas, Alberto

    2015-10-01

    Full Text Available Penzias and Wilson discovered the cosmic microwave background, a luminous echo of the Big Bang, in 1965. The amount of information encoded in this relic of the early universe is truly extraordinary. At present, the most precise data about the origin and structure of the universe comes from the study of this primordial light, the full potential of which has yet to be explored.En 1965 se descubrió el fondo de radiación de microondas, un eco luminoso de la Gran Explosión (Big Bang. La cantidad de información contenida en esta reliquia del universo primitivo es verdaderamente extraordinaria. En la actualidad los datos más precisos sobre el origen y estructura del universo provienen del estudio de esta luz primigenia, que aún no ha sido explorada en todo su potencial.

  2. Dimensoni di impresa, divisioni del lavoro e ampiezza del mercato. (Firm size and the division of labor

    Directory of Open Access Journals (Sweden)

    B. CONTINI

    2013-12-01

    Full Text Available La recente pubblicazione del 1981 del Censimento industriale in Italia ha messo in evidenza un fenomeno di cui vi erano già stati alcuni segni da un certo numero di anni - il fatto che le imprese manifatturiere di ogni settore stanno riducendo le loro dimensioni. I dati indicano che sia l'aspetto di un gran numero di piccole imprese nuove e la riduzione del numero medio dei dipendenti delle imprese esistenti di tutte le dimensioni hanno contribuito a questo . Conclusioni simili sono state tratte per gli altri paesi europei. L'ipotesi dell'autore è che la riduzione osservata della dimensione media delle imprese è causata da due fattori concomitanti: ( 1 la maggiore rigidità della struttura dei costi complessivi delle imprese commerciali; ( 2 la maggiore incertezza nei mercati dei fattori e dei prodotti , il che rende le strutture organizzative più flessibili desiderabile .The recent publication of Italy’s 1981 Industrial Census has highlighted a phenomenon of which there had already been some signs for a number of years - the fact that manufacturing firms in every sector are reducing their size. The data indicate that both the appearance of a large number of small new firms and the reduction in the average number of employees in existing firms of all sizes have contributed to this. Similar conclusions have been drawn for other European countries. The author’s hypothesis is that the observed reduction in the average size of firms is caused by two concurrent factors: (1 the increased rigidity of the overall cost structure of business firms; (2 the increased uncertainty in both factor and product markets, which makes more flexible organisational structures desirable.JEL: L16, L60, O14

  3. Genotipi e mutanti del gene S del virus dell'epatite B (HBV in soggetti con infezione cronica

    Directory of Open Access Journals (Sweden)

    E. Tanzi

    2003-05-01

    Full Text Available

    Il virus dell’epatite di tipo B (HBV presenta 7 genotipi (A-G, distinti in base alla sequenza genomica pre-S/S. Mutazioni in tale regione, in particolare nell’epitopo immunodominante dell’HBsAg (determinante a, permettono la selezione di “escape mutants” che sfuggono alla risposta immunitaria dell’ospite.

    Obiettivi: indagare la distribuzione dei genotipi di HBV circolanti in Italia e valutare le possibili associazioni con i fattori di rischio; studiare la prevalenza delle varianti “escape” nell’ambito di una sorveglianza di tipo epidemiologico.

    Metodi: in uno studio retrospettivo sono stati analizzati campioni di siero provenienti da 34 soggetti (27M, 7F; età media 42.2 anni, range 25-75 HBV/HIV-1co-infetti e da 24 pazienti (16M, 8F; età media 47.9 anni, range 24-82 con infezione cronica da HBV. I genotipi di HBV e le varianti virali sono state indagate mediante amplificazione, sequenziamento ed analisi filogenetica di un frammento di 1182 pb della regione pre-S/S. Risultati: la determinazione dei genotipi di HBV in 25/34 campioni da soggetti HBV/HIV+ ha evidenziato 12 genotipi D (48%, 8 A (32%, 4 G (16%, ed 1 B (4%; in 23/24 pazienti con infezione cronica da HBV sono stati riscontrati 13 D (56.5%, 7 A (30.4%, 2 F (8.7% ed 1 E (4.4%. Mutazioni nel determinante a sono risultate presenti in 8/25 (32% pazienti HIV/HBV+, di cui 3/8 (37.5% a livello del primo loop, 2/8 (25% del secondo, mentre in 3/8 casi (37.5% mutazioni erano presenti in entrambe le regioni.

    Conclusioni: i genotipi più diffusi appaiono il D e l’A. Tra gli HIV/HBV+ il D sembra associato alla tossicodipendenza (80%. Degno di nota il riscontro di 4 soggetti con genotipo G (16% tra gli HIV/HBV+, prima segnalazione nel nostro Paese e di 3 soggetti (13% con genotipo F o E, non endemici in Italia. Mutazioni nel gene S sembrano correlare con il genotipo D e la tossicodipendenza.

  4. Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway.

    Science.gov (United States)

    Kiranmayi, Malapaka; Chirasani, Venkat R; Allu, Prasanna K R; Subramanian, Lakshmi; Martelli, Elizabeth E; Sahu, Bhavani S; Vishnuprabu, Durairajpandian; Kumaragurubaran, Rathnakumar; Sharma, Saurabh; Bodhini, Dhanasekaran; Dixit, Madhulika; Munirajan, Arasambattu K; Khullar, Madhu; Radha, Venkatesan; Mohan, Viswanathan; Mullasari, Ajit S; Naga Prasad, Sathyamangla V; Senapati, Sanjib; Mahapatra, Nitish R

    2016-08-01

    Catestatin (CST), an endogenous antihypertensive/antiadrenergic peptide, is a novel regulator of cardiovascular physiology. Here, we report case-control studies in 2 geographically/ethnically distinct Indian populations (n≈4000) that showed association of the naturally-occurring human CST-Gly364Ser variant with increased risk for hypertension (age-adjusted odds ratios: 1.483; P=0.009 and 2.951; P=0.005). Consistently, 364Ser allele carriers displayed elevated systolic (up to ≈8 mm Hg; P=0.004) and diastolic (up to ≈6 mm Hg; P=0.001) blood pressure. The variant allele was also found to be in linkage disequilibrium with other functional single-nucleotide polymorphisms in the CHGA promoter and nearby coding region. Functional characterization of the Gly364Ser variant was performed using cellular/molecular biological experiments (viz peptide-receptor binding assays, nitric oxide [NO], phosphorylated extracellular regulated kinase, and phosphorylated endothelial NO synthase estimations) and computational approaches (molecular dynamics simulations for structural analysis of wild-type [CST-WT] and variant [CST-364Ser] peptides and docking of peptide/ligand with β-adrenergic receptors [ADRB1/2]). CST-WT and CST-364Ser peptides differed profoundly in their secondary structures and showed differential interactions with ADRB2; although CST-WT displaced the ligand bound to ADRB2, CST-364Ser failed to do the same. Furthermore, CST-WT significantly inhibited ADRB2-stimulated extracellular regulated kinase activation, suggesting an antagonistic role towards ADRB2 unlike CST-364Ser. Consequently, CST-WT was more potent in NO production in human umbilical vein endothelial cells as compared with CST-364Ser. This NO-producing ability of CST-WT was abrogated by ADRB2 antagonist ICI 118551. In conclusion, CST-364Ser allele enhanced the risk for hypertension in human populations, possibly via diminished endothelial NO production because of altered interactions of CST-364Ser

  5. Archivo del Duelo

    OpenAIRE

    Ferrera, Tamara

    2010-01-01

    Photos taken from the Archive of Mourning following the March 11 terrorist attacks El Archivo del Duelo. Creación de un archivo etnográfico de los Atentados del 11 de marzo en Madrid. Ministerio de Educación y Ciencia HUM2005-03490.

  6. Displasias del seno

    Directory of Open Access Journals (Sweden)

    Ernesto Andrade Valderrama

    1971-04-01

    Full Text Available En general, las Displasias no se presentan antes de la iniciación del estímulo Gonadal y tienden a desaparecer con el climaterio. Se definen entonces como las afecciones benignas del Seno, de origen endocrino.

  7. La disciplina delle emozioni tra introspezione e performance: pratiche e discorsi del controllo a Toraja (Indonesia

    Directory of Open Access Journals (Sweden)

    Aurora Donzelli

    2013-07-01

    Full Text Available La letteratura antropologica sulle emozioni relativa alle società dell’Indonesia e dell’area più vasta che comprende il Sudest asiatico e il Pacifico sembra convergere sull’enfasi attribuita alla questione del controllo emozionale3. Gli antropologi che hanno lavorato in quest’area sono stati inevitabilmente affascinati dalla compostezza e dall’assenza di espressione diretta dei sentimenti dimostrata nel comportamento quotidiano delle persone che cercavano di comprendere (Anderson 1966, p. 129; Belo 1935 [1970]; Bateson, Mead 1942; Bonokamsi 1972; Connors 1979; Errington 1984, 1983; Geertz 1958, 1960,1966, 1983; Geertz 1961, 1959; Just 1991; Hollan 1988; Hollan, Wellenkamp 1994, 1996; Keeler 1987; Wellenkamp 1984, 1988b; Wikan 1989.

  8. Period Drama Men e altri oggetti del desiderio. Fanvidding 2.0

    Directory of Open Access Journals (Sweden)

    Donata Meneghelli

    2016-10-01

    Full Text Available Il saggio analizza una delle manifestazioni più diffuse e interessanti del media fandom, il remix audiovisivo, e i suoi rapporti con la serialità. Si tratta di una forma di appropriazione da parte dei fan che consiste – nella maggioranza dei casi – nel prelevare e (rimontare brevi sequenze tratte da fonti audiovisive mainstream (film, serie televisive, spesso accompagnandole con uno o più brani musicali. I video che scaturiscono da questa pratica, e che vengono condivisi su piattaforme di videosharing come YouTube o Vimeo, esplorano la fonte o le fonti in modi inediti.  Dopo una ricognizione che mette in luce il carattere strutturalmente seriale della pratica del fanvidding, ricostruendone la genesi e mostrandone gli sviluppi più recenti, in parallelo alle trasformazioni che negli ultimi anni hanno investito tanto la fisionomia del fandom quanto le tecnologie digitali, il saggio prende come corpus di riferimento i video prodotti nell’ambito delle comunità o da utenti/produttori che gravitano intorno al period drama. A partire da una discussione di alcune delle classificazioni e tipologie correnti (fake/fan trailer, redub, supercut…, e basandosi in parte sulle categorie proposte da Gérard Genette in Palimpsestes, vengono proposti tre criteri – relazione con la fonte, regime, logica – attraverso i quali analizzare i video prodotti dai fan. Tali criteri consentono di mettere a fuoco alcune questioni cruciali come l’atteggiamento degli utenti/produttori nei confronti della fonte, del materiale ri-assemblato, i potenziali effetti di ricezione, la funzione del commento musicale nell’ibridazione di generi e forme, la ripetizione come modalità fondamentale di espressione del desiderio ma anche come strumento di lettura critica, le implicazioni (e le contraddizioni di quella che è stata definita da Kristina Busse «estetica [meta] affettiva».

  9. OBJETIVO DEL DESARROLLO DEL MILENIO 7

    Directory of Open Access Journals (Sweden)

    Margarita M. Pérez O.

    2013-10-01

    Full Text Available Los Objetivos de Desarrollo del Milenio, también conocidos como los Objetivos del Milenio, constituyeron las metas finales que aprobaron los dirigentes mundiales, 189 jefes de estado y de gobierno en la Cumbre del Milenio de las Naciones Unidas celebrada en Nueva York en el año 2000, en la cual los Estados miembros de la organización reafirmaron su compromiso de luchar por un mundo en el que el desarrollo sostenible y la eliminación de la pobreza tuvieran máxima prioridad1 . En la cumbre se definió la Declaración del Milenio, la cual detalla los objetivos, principios, valores, metas y acciones para erradicar la pobreza Mundial hacia el año 2015, todos ellos ratificados con alto interés y acción estratégica de carácter global, como marco para la medición de los progresos en materia de desarrollo.

  10. Elementos del sistema electoral del Congreso Mexicano

    Directory of Open Access Journals (Sweden)

    Aldo Medina García

    2013-08-01

    Full Text Available El presente artículo es un estudio de los componentes del sistema electoral, diseñado por el legislador mexicano para integrar al parlamento federal. Estudio desarrollado a sabiendas de la importancia que reviste el sistema electoral como un medio que permite a los ciudadanos convertir su voto expresado en las urnas en escaños a favor de determinado candidato o partido. En dicho análisis tomamos en cuenta la evolución constitucional del sistema electoral mexicano, la participación de las fuerzas minoritarias en la integración del Senado y de la Cámara de Diputados, la división que se hace del territorio en circunscripciones electorales, la barrera electoral que se fija a los partidos políticos para acceder a la representación en el Parlamento, la fórmula de asignación que se aplica a la votación obtenida, para finalmente concluir que el sistema electoral mexicano es esencialmente mayoritario aun cuando se vista de proporcional.

  11. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia.

    Science.gov (United States)

    Bhuvanendran, Saatheeyavaane; Hussin, Hani M; Meran, Lila P; Anthony, Amy A; Zhang, Leilei; Burch, Lauranell H; Phua, Kia K; Ismail, Asma; Balaram, Prabha

    2011-09-01

    Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p = 0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p population and suggests that these polymorphisms confer a higher risk for typhoid, infection. The higher incidence of typhoid fever in Kelantan could be attributed to the higher percentage of Malays (95%) in this state. In order to reduce the incidence of this disease, people with these polymorphisms, can be prioritised for prophylactic strategies. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  12. Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    International Nuclear Information System (INIS)

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

    1987-01-01

    To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance

  13. Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo

    Science.gov (United States)

    Reinhardt, Robert; Centanin, Lázaro; Tavhelidse, Tinatini; Inoue, Daigo; Wittbrodt, Beate; Concordet, Jean-Paul; Martinez-Morales, Juan Ramón; Wittbrodt, Joachim

    2015-01-01

    Transcriptional networks defining stemness in adult neural stem cells (NSCs) are largely unknown. We used the proximal cis-regulatory element (pCRE) of the retina-specific homeobox gene 2 (rx2) to address such a network. Lineage analysis in the fish retina identified rx2 as marker for multipotent NSCs. rx2-positive cells located in the peripheral ciliary marginal zone behave as stem cells for the neuroretina, or the retinal pigmented epithelium. We identified upstream regulators of rx2 interrogating the rx2 pCRE in a trans-regulation screen and focused on four TFs (Sox2, Tlx, Gli3, and Her9) activating or repressing rx2 expression. We demonstrated direct interaction of the rx2 pCRE with the four factors in vitro and in vivo. By conditional mosaic gain- and loss-of-function analyses, we validated the activity of those factors on regulating rx2 transcription and consequently modulating neuroretinal and RPE stem cell features. This becomes obvious by the rx2-mutant phenotypes that together with the data presented above identify rx2 as a transcriptional hub balancing stemness of neuroretinal and RPE stem cells in the adult fish retina. PMID:25908840

  14. Continuing evolution of canine parvovirus in China: Isolation of novel variants with an Ala5Gly mutation in the VP2 protein.

    Science.gov (United States)

    Wang, Jianke; Lin, Peng; Zhao, Hang; Cheng, Yuening; Jiang, Zhong; Zhu, Hongwei; Wu, Hua; Cheng, Shipeng

    2016-03-01

    Canine parvovirus (CPV) type 2c is a new antigenic variant of CPV-2. Since the year 2000 it has spread to several countries, causing severe hemorrhagic enteritis in dogs. In 2014 and 2015, 58 fecal samples were collected from dogs in Beijing with suspected CPV infection. Regardless of the vaccination status of the dogs, 43 samples were found positive for CPV according to PCR results; i.e., 18, 7, and 18 respectively belonged to antigenic types new CPV-2a, new CPV-2b, and CPV-2c. A phylogenetic tree based on their VP2 gene sequences indicated that the Chinese CPV-2c strains form a separate cluster. In addition to synonymous mutations, the CPV-2c strains also contain a unique coding mutation in VP2 that leads to glycine at residue 5, instead of the highly conserved alanine at this position in all other CPV-2c strains sequenced to date. Using F81 cells, several novel isolates of CPV-2c, each with the Ala5Gly mutation, were obtained. One of these was used to infect experimentally beagle dogs, which subsequently developed the typical clinical symptoms of CPV infection. Hence, it appears that CPV-2c is still evolving in China, a finding that warrants continuous surveying and the eventual adaptation of current vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Sedimentology and biostratigraphy of the Early-Middle Miocene transition in NW Transylvanian Basin (Pâglişa and Dej sections

    Directory of Open Access Journals (Sweden)

    Claudia Beldean

    2013-01-01

    Full Text Available The Early - Middle Miocene transition can be studied in several sections from the north-western Transylvanian Basin, across the boundary between the Hida and Dej Formations. The Pâglişa and Râpa Dracului (Dej locally outcrop sections offer a very good record of the changes in the sedimentary facies and micropaleontological content across the boundary. The lower parts of the sections display the upper Hida Formation with prodelta fine grained sediments covered by coarser grained sediments related to a delta front progradation. Four sedimentary facies associations have been separated based on grain size and associated sedimentary structures. Micropaleontological assemblages are moderately to poorly preserved, with a low abundance and diversity. Planktonic Streptochilus pristinum is the main taxon associated with rare (< 10% calcareous benthic foraminifera (Bulimina, Bolivina, Cibibicidoides. The Dej Formation consists of stacked channel lag deposits associated with lateral accretion bars and crevasse splays followed by fall-out tuffs and redeposited low density tuffites interbedded with low density fine siliciclastics. The deposits of Dej Formation from the investigated areas were separated in four facies associations based on grain size/petrography and primary sedimentary structures. Micropaleontological assemblages contain typical early Badenian planktonic foraminifera (species of Orbulina, Praeorbulina, Globigerinoides, and Globorotalia associated to the main phase of the marine transgresion from the beginning of the Middle Miocene.

  16. Over-expression of Arabidopsis thaliana SFD1/GLY1, the gene encoding plastid localized glycerol-3-phosphate dehydrogenase, increases plastidic lipid content in transgenic rice plants.

    Science.gov (United States)

    Singh, Vijayata; Singh, Praveen Kumar; Siddiqui, Adnan; Singh, Subaran; Banday, Zeeshan Zahoor; Nandi, Ashis Kumar

    2016-03-01

    Lipids are the major constituents of all membranous structures in plants. Plants possess two pathways for lipid biosynthesis: the prokaryotic pathway (i.e., plastidic pathway) and the eukaryotic pathway (i.e., endoplasmic-reticulum (ER) pathway). Whereas some plants synthesize galactolipids from diacylglycerol assembled in the plastid, others, including rice, derive their galactolipids from diacylglycerols assembled by the eukaryotic pathway. Arabidopsis thaliana glycerol-3-phosphate dehydrogenase (G3pDH), coded by SUPPRESSOR OF FATTY ACID DESATURASE 1 (SFD1; alias GLY1) gene, catalyzes the formation of glycerol 3-phosphate (G3p), the backbone of many membrane lipids. Here SFD1 was introduced to rice as a transgene. Arabidopsis SFD1 localizes in rice plastids and its over-expression increases plastidic membrane lipid content in transgenic rice plants without any major impact on ER lipids. The results suggest that over-expression of plastidic G3pDH enhances biosynthesis of plastid-localized lipids in rice. Lipid composition in the transgenic plants is consistent with increased phosphatidylglycerol synthesis in the plastid and increased galactolipid synthesis from diacylglycerol produced via the ER pathway. The transgenic plants show a higher photosynthetic assimilation rate, suggesting a possible application of this finding in crop improvement.

  17. Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico

    Directory of Open Access Journals (Sweden)

    Hugo Cruz-Hipolito

    2015-09-01

    Full Text Available Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor. These herbicides are classified into three major families (ariloxyphenoxypropionates (APP, cyclohexanodiones (CHD, and, recently, phenylpyrazolines (PPZ. In this work, the resistance to ACCase (APP, CHD, and PPZ inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the 14C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations.

  18. Use of GIS techniques for hydro-geological water balance assessment at regional scale; Impiego di tecniche GIS per la valutazione e rappresentazione del bilancio idrogeologico a scala regionale

    Energy Technology Data Exchange (ETDEWEB)

    De Girolamo, A. M.; Limoni, P. P.; Portoghese, I.; Vurro, M. [Consiglio Nazionale delle Ricerche, Istituto di Ricerca sulle Acque, Reparto Sperimentale di Bari, Bari (Italy)

    2001-04-01

    The aim of the present work is to assess the hydro-geological water balance of the soil and subsoil system. At the beginning, the natural groundwater recharge evaluated as the subtraction between the soil inflows (rainfall) and outflows (evapotranspiration, surface runoff) enable to determine the soil water balance. Then, in order to calculate the subsoil water balance, the withdrawals for different purposes have been estimated together with the inflows coming from other water bodies and the coastal outflows. This method has been applied through a GIS technique; in particular, after the data layers acquisition (climatic, topographic, geologic, land use, satellite images, etc.), the numerical calculation has been done and several thematic output maps have been obtained. The method has been applied to the whole Apulian region; in this work, only the results about Salento Peninsula have been reported. The results highlight a significant water resources deficit; this deficit is also confirmed by the deepening of groundwater piezometric heads and the increase of chlorine ions, measured, for more than 10 years, in some characteristic points located in the study area. [Italian] Scopo del presente lavoro e' valutare il bilancio idrogeologico mediante il bilancio di massa per il sistema rappresentato dal complesso suolo e sottosuolo. Inizialmente e' stato valutato il bilancio idrico del suolo che ha consentito di determinare la ricarica naturale della falda per differenza tra gli ingressi al sistema suolo (apporti meteorici) e le uscite dal suolo agrario e dalle colture (evapotraspirazione), ed il deflusso superficiale. Successivamente, per calcolare il bilancio di massa del sistema sottosuolo sono stati stimati gli emungimenti per i diversi usi, gli afflussi provenienti da altri corpi idrici sotterranei e gli efflussi a mare. La metodologia e' stata implementata utilizzando una tecnologia GIS; in particolare, dopo l'acquisizione dei diversi strati

  19. Castillo del Real. Olocau

    OpenAIRE

    AUÑÓN VALLEJO, JONATAN

    2012-01-01

    El objetivo que se quiere alcanzar con este proyecto es el de realizar un estudio lo más cercano posible del Catillo del Real, de manera que se pueda conocer su origen, su evolución a lo largo de la historia, así como las diferentes técnicas y sistemas constructivos utilizados en su construcción. Auñón Vallejo, J. (2011). Castillo del Real. Olocau. http://hdl.handle.net/10251/14244. Archivo delegado

  20. La Representabilidad del Genocidio

    OpenAIRE

    Cardona González, Lorena

    2012-01-01

    El presente artículo intenta hacer una aproximación histórica y analítica al fenómeno del Genocidio, sus implicaciones sociales y culturales que dieron como resultado la reformulación analítica y conceptual de hechos que hasta entonces superaban el conocimiento y la moral humana. De este modo, se hace un trayecto histórico de la paulatina aparición del asesinato masivo como practica de Estado, enmarcado en las experiencias del genocidio armenio y el alemán. A su vez, se hace una mirada sobre ...

  1. Significado presente del CSIC

    OpenAIRE

    Garrido Gallardo, Miguel Angel

    2000-01-01

    Not available

    Este artículo, elaborado en 1999, ofrece una panorámica de la realidad del Consejo Superior de Investigaciones Científicas en la actualidad. Repasa su organización, su volumen de publicaciones, sus indicadores de productividad, su capacidad de obtener recursos y, en suma, su lugar en el conjunto del sistema español de Ciencia y Tecnología, considerado en sí mismo y en relación con la Universidad. Como conclusión del repaso de datos, se afirma que, aunque la fó...

  2. Tratamiento del pie equino

    OpenAIRE

    Robles, Fernanda

    2012-01-01

    El pie equino varo es una patología frecuente en los pacientes con Encefalopatía crónica no evolutiva (ECNE).Se observó que existe una mayor frecuencia en el sexo masculino. Se realizó un estudio descriptivo, comparativo y secundario, durante el periodo de septiembre del 2006 a septiembre del 2011, con un total de 125 pacientes con Ecne, de los cuales se encontraron 101 con pie equino varo congénito. Objetivo: observar los resultados obtenidos en la rehabilitación del pie equino, en niños de ...

  3. Del Pasadismo al Futurismo

    OpenAIRE

    Agudo-Martínez, M. J.

    2003-01-01

    Uno de los habituales prejuicios a la hora de abordar el análisis del movimiento futurista, al igual que sucede con el constructivismo, es la consideración del contexto político en el que se desarrollaron ambas vanguardias. Sin embargo, y dejando a un lado un enfoque del arte con finalidad política de signo diverso, habría que insistir en el hecho de que posiblemente sean tanto el futurismo italiano como el constructivismo ruso, los movimientos que con mayor entusiasmo se manifestaron, en un ...

  4. Il nuovo ortofotopiano del Comune di Venezia nell’Infrastruttura dei dati Territoriali di Base (ITB

    Directory of Open Access Journals (Sweden)

    Paolo Barbieri

    2006-06-01

    Full Text Available Il Comune di Venezia, nell’ambito delle attività per lo sviluppo del proprio Sistema Informativo Territoriale, ha messo a punto e avviato a realizzazione uno specifico progetto per la costruzione di un’Infrastruttura di dati Territoriali di Base (ITB. Il progetto, che ha visto il coinvolgimento dei vari Uffici comunali interessati, dellaRegione del Veneto e dell’Agenzia del Territorio, si è sviluppato a partire dal 2002 con gli studi di fattibilità, cui è seguita nel 2003 la fase della progettazione esecutiva e quindi, a partire dal 2004, dell’attuazione. Attualmente le componenti dell’infrastruttura sono state realizzate e si sta procedendo alla definizione di una piattaforma tecnologica per la gestione e l’utilizzo della ITB, basata su di un Geo-DBMS e meccanismi di interoperabilità, con l’obiettivo di interfacciare le diverse applicazioni gestionali presenti in Comune. Nel presente articolo si intende presentare il modello concettuale di riferimento ed evidenziare, in particolare, il ruolo in esso svolto dalle immagini ortofotografiche.

  5. Pratiche narrative. L’esperienza del Laboratorio Urbano Aperto in Salento

    Directory of Open Access Journals (Sweden)

    Laura Basco

    2009-06-01

    Full Text Available L’esperienza di ricercazione del LUA (Laboratorio Urbano Aperto1 è iniziata con una e-mail fatta girare da un nucleo di giovani salentini, tre architetti – legati alla facoltà di architettura di Firenze – e una sociologa. L’invito a partecipare a un laboratorio urbano di esperienze conoscitive, che aveva l’obiettivo di mettere a confronto diverse riflessioni sull’identità del piccolo paese di San Cassiano, a partire dal contatto con gli abitanti, era diretto ad un piccolo gruppo di amici e conoscenti che, giorno dopo giorno – tramite il web e il passaparola – è aumentato spontaneamente fino ad radunare il 3 agosto 2003, giorno di apertura del primo laboratorio, ben 61 persone di diversa provenienza. “Qualcuno che faceva base a San Cassiano, durante i due mesi precedenti, aveva stampato e fotocopiato l’invito e ne parlava ogni sera al bar... Questa cosa suscitava un certo interesse e una crescente aspettativa”.

  6. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

    Science.gov (United States)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

  7. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

    International Nuclear Information System (INIS)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-01-01

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17α-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERα-selective agonist), diarylpropionitrile (DPN, an ERβ-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERα-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERβ-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

  8. Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10-NH2 at the human melanocortin-1 and -4 receptors: DPhe7 and Trp9 substitution.

    Science.gov (United States)

    Danho, Waleed; Swistok, Joseph; Cheung, Adrian Wai-Hing; Kurylko, Grazyna; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-02-24

    A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Nal and Bta) were identified in this study.

  9. Preferencias del Turista

    Directory of Open Access Journals (Sweden)

    Jose Luis Leiva Olivencia

    2015-01-01

    Full Text Available Actualmente existen aplicaciones orientadas al turismo basadas en realidad aumentada, pero no integran técnicas de recomendación. Este articulo describe RAMCAT (Realidad Aumentada Móvil Contextual Aplicada al Turismo un modelo de guía turística, que recomienda puntos de interés, teniendo en cuenta factores como preferencias personales y atributos contextuales. Se presentan los componentes teóricos de la arquitectura propuesta, así como sus características, destacando la integración de diferentes sistemas de recomendación, que permiten añadir nuevos motores en el futuro. El articulo se centra en describir sus funcionalidades y el modulo correspondiente al sistema de recomendación basado en el perfil del turista. Otra característica importante del sistema propuesto es la retroalimentación del mismo mediante calificaciones del turista y su trazabilidad.

  10. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available La millonaria contratación del futbolista David Beckham, un fenómeno del mercado, ha provocado cuestionamientos a los que se busca respuesta. Es tema de análisis el por qué el betseller "Harry Potter" ha causado tanta conmoción en la opinión pública. Respecto al periodista cibernético, se señalan los contornos del presente y atisban las posibilidades del futuro de esta nueva profesión. El tratamiento de los mitos de la prensa, los temores de la Ley mordaza venezolana y la brutalidad de los video juegos e Internet son temas de enorme interés. Se comenta las pocas veces que la prensa reflexiona sobre la comunicación corporal y la anorexia.

  11. Los muertos del Floreanismo

    Directory of Open Access Journals (Sweden)

    Enrique Ayala Mora

    2008-06-01

    Full Text Available El artículo analiza el crimen político durante las primeras décadas de vida de la República del Ecuador. Específicamente centra su estudio en el período dominado por la figura de Juan José Flores, primer presidente del Ecuador. La inestabilidad política, la precariedad de las alianzas entre las élites regionales, la crisis económica generada por las guerras de Independencia, las conspiraciones y la violencia que caracterizaron al período de surgimiento de las repúblicas andinas hicieron del crimen político un “vicio de nacimiento”. El asesinato del general Antonio José de Sucre, la muerte de los miembros de la sociedad El Quiteño Libre, el homicidio de Juan Otamendi, entre otros, hicieron patente esta característica.

  12. Niveles del aprendizaje organizacional

    OpenAIRE

    Garzón Castrillón, Manuel Alfonso

    2005-01-01

    En la propuesta de modelo de aprendizaje organizacional (AO), la segunda variable se denomina niveles del aprendizaje organizacional ; los niveles de aprendizaje que contemplamos para nuestra investigación son: individual, de equipo, organizacional e interorganizacional.

  13. La escritura del Yo

    Directory of Open Access Journals (Sweden)

    Patricio Landaeta Mardones

    2013-11-01

    Full Text Available Si la creación de una imagen fidedigna del mundo fue la condición de la conquista cognitiva y económica de la tierra, las imágenes mediáticas circulan hoy en día a la manera de un montaje que organiza los sujetos como elementos de un territorio. En esta presentación abordaremos el cruce entre estos dos hechos, entre la escritura del mundo y la de los sujetos, a partir de la idea de Fabulación para mostrar otra escritura del mundo y del yo, leyendo textos e imágenes de la Primera buena Corónica y Buen Gobierno de Felipe Guaman Poma de Ayala.

  14. Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish

    Directory of Open Access Journals (Sweden)

    van Eeden Freek

    2010-04-01

    Full Text Available Abstract Background In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. Results Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation. Conclusion Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.

  15. Consideraciones alrededor del Libro del Almismo, el Libro del Pensar.

    Directory of Open Access Journals (Sweden)

    MartaLucía Tamayo Fernandez

    1999-12-01

    Full Text Available

    La doctora MarthaLucía Tamayo comparte muchas inquietudes alrededor del Libro del Almismo, el Libro del Pensar; de dónde salió ese nombre; de juntar en medicina y en genética a tres escritores como lo son Jorge Luis Borges, Macedonio Fernández y Julio Cortázar. Su conferencia dice así:

    El término almismo fue ideado por Macedonio Fernández porque defendía mucho el ensimismamiento y el pensamiento hacia el interior, mirar hacia adentro; cada uno somos un “sí mismo” que nos hace diferentes aunque al mismo tiempo podemos ser iguales. Todos tenemos esa parte interior que la medicina debe trabajar y que no puede olvidar.

    “El Libro del Almismo, el libro del pensar” nos lleva a replantear y a repensar un poco la medicina que queremos, una medicina vuelta a pensar.

    Quiero contarles la historia de cómo se llegó a este libro y por qué y para qué se sigue trabajando en estos temas: Después de mi internado y de un trabajo un poco triste de rural, volví al Instituto de Genética y a la Universidad Javeriana en donde encontré al doctor Bernal y un espacio que estaba buscando para esa medicina diferente que quería, con un grupo de personas que me permitía no sólo ver la medicina sino ver muchas otras cosas más; había espacio para la literatura, para Mafalda, para hablar de niños, de locos, había incluso tiempo para hablar de medicina dentro del golf, de carros antiguos y de todo eso fui aprendiendo.

    Eso era lo que estaba buscando. Una medicina que diera espacios diferentes, que fuera más humanizada. Rápidamente me ubiqué y me quedé! No me arrepiento en lo absoluto de haberme quedado porque fue, ha sido y sigue siendo, una experiencia enriquecedora, de muchas vivencias importantes. Sabía exactamente dónde estaba y sabía que había que seguir rápido y había que trabajar muchos aspectos de esa medicina que estábamos buscando y de esa genética especial.

    Rápidamente empezamos a trabajar

  16. Actualidad del relativismo cultural

    OpenAIRE

    Sánchez Durá, Nicolás

    2013-01-01

    Este ensayo tiene tres propósitos. En primer lugar, propone examinar las relaciones entre etnocentrismo y relativismo. El etnocentrismo puede tomar tres formas distintas: a saber, la de una universalidad impostada, la del exotismo y la de un particularismo narcisista exacerbado. El relativismo cultural es una postura que asume la inconmensurabilidad de los conceptos y valores que deben ser considerados como válidos dentro de las imágenes del mundo definidas. En segundo lugar, se argumenta que...

  17. el Valle del Cauca

    Directory of Open Access Journals (Sweden)

    Carlos Humberto Ortiz

    2007-01-01

    Full Text Available Este artículo se enfoca en la identi- ficación de aquellos factores estructurales que explican la pérdida de dinamismo económico de largo plazo en Colombia y, en particular, en el Valle del Cauca. Se examina la competitividad del Valle en relación con Colombia y con el resto del mundo. Se cuestiona la insistencia en una estrategia exportadora como dinamizadora del desarrollo económico. Se identifica que una gran parte de la población está excluida de los beneficios del desarrollo económico. Para construir un modelo de desarrollo que incluya a esta población se recomienda recuperar la senda de la industrialización, invertir en el capital humano (educación de alta calidad, salud, salubridad y nutrición, e invertir en infraestructura. La participación del Estado en estas inversiones sociales es necesaria para disminuir la desigualdad y aumentar el crecimiento económico.

  18. Espectroscopia del Cometa Halley

    Science.gov (United States)

    Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

    1987-05-01

    Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

  19. Inventario nacional del uso actual del agua

    OpenAIRE

    Oficina Nacional de Evaluación de Recursos Naturales

    1984-01-01

    Establece como se emplea el agua en el Perú, teniendo en cuenta el tipo de uso, consuntivo y no consuntivo, discriminando según sea el destino: agrícola, pecuario, poblacional,industrial, minero, energético y pesquero, así como su localización geográfica; ello con la finalidad de que sirva de información básica para la planificación del desarrollo.

  20. The role of composting from the point of view of Agenda 21; Il ruolo del compostaggio nell'ottica dell'Agenda 21

    Energy Technology Data Exchange (ETDEWEB)

    Chierici, F.

    1999-10-01

    Agenda 21 is more and more often mentioned in debates and meetings dealing with environment, economy and development. How to actually make the aims enunciated in what is to be considered the next century programmatic document effective is, on the contrary, hardly outlined. The aim of this article is to help in making interaction between Agenda 21 and product reality more tangible and evident, specifically as far as composting is concerned. After an analytical description of the document, the points of contact between Agenda 21 and composting are identified: each one is highlighted through a rich bibliography. [Italian] L'Agenda 21 e' sempre piu' spesso ricordata all'interno dei dibattiti e degli incontri che trattano d'ambiente, economia e sviluppo. I modi attraverso i quali contestualizzare in pratica gli obiettivi enunciati in quello che va considerato come il documento programmatico del prossimo secolo sono invece spesso solo tratteggiati. Quest'articolo vuole essere percio' un contributo per rendere piu' tangibile e visibile l'interazione esistente tra l'Agenda 21 e la realta' produttiva; nel caso specifico il compostaggio. Dopo una descrizione analitica del documento, sono individuati in modo formale i punti di contatto tra gli obiettivi dell'Agenda 21 ed il compostaggio: ciascuno di loro e' messo in evidenza facendo riferimento ad un'ampia bibliografia.

  1. Gerencia del cuidado-gerencia del servicio

    Directory of Open Access Journals (Sweden)

    Marta Palmet Jiménez

    2016-01-01

    Full Text Available La gerencia de este siglo debe estar plenamente identificada con la administración para planear, organizar, decidir y obtener resultados definidos, evaluados y alcanzados a través de las personas. Para poder gerenciar el cuidado se debe saber administrar. El objetivo de enfermería es cuidar; el objetivo de la gerencia es la conducción de la producción de bienes o servicios en las organizaciones. La gerencia del cuidado implica: motivación, creatividad, responsabilidad y ética por parte del cuidador y de quien cuida, claridad de actitud frente al ser y al qué hacer por parte del cuidador. Se puede concluir que la gerencia (administración, el cuidado (producto de calidad, el servicio (valor intangible, querer servir son un trinomio que deben ir de la mano de manera integrada para el logro de los objetivos propuestos por la organización de salud y de enfermería.

  2. Studi d'idoneità ambientale su grande scala a fini conservazionistici: il caso del Capriolo italico nel P.N. del Pollino

    Directory of Open Access Journals (Sweden)

    Alessandro Massolo

    2003-10-01

    Full Text Available Nonostante la loro grande diffusione negli ultimi decenni, i modelli di valutazione ambientale (MVA trovano tuttoggi scarsa applicazione pratica. Molte difficoltà s?incontrano non solo nel loro concreto utilizzo, ma anche nella validazione e applicazione. Spesso, il problema fondamentale consiste nella difficoltà di reperire dati biologici e geografici su grande scala che siano attendibili e omogenei. La gestione spesso però richiede valutazioni su grande scala e il problema diventa quindi rilevante. Nel presente lavoro sono descritte alcune procedure di modellizzazione e verifica a partire dai risultati di uno studio condotto sul capriolo nel Parco Nazionale del Pollino. A tale scopo, sono state utilizzate due delle più diffuse tecniche statistiche multivariate (Analisi della Funzione Discriminante e Regressione Logistica, confrontando modelli formulati con e senza l?uso di indici di complessità del paesaggio come variabili predittive. L?analisi è stata condotta a grande scala compatibilmente con le stime delle dimensioni degli home range della specie. Lo sviluppo di più modelli ha permesso di verificare l?adeguatezza delle tecniche utilizzate e l?efficacia dei più comuni indici di paesaggio, nel predire la distribuzione della specie. Le analisi ambientali sono state effettuate mediante l?uso di ArcView 3.2 e della sua estensione Patch Analyst, a partire da cartografia informatizzata come la carta di uso del suolo Corine Land Cover e i punti quotati IGMI. I modelli sono stati formulati da un set di dati provenienti dell?Appennino centro-settentrionale e validati con un set di dati locali (area di distribuzione e avvistamenti diretti, raccolti tra il 2001 e il 2003. Il confronto tra i modelli si è basato sulle loro capacità di classificazione (sensitività e sensibilità. Gli indici di paesaggio sono risultati critici nel predire correttamente la distribuzione della specie. Nella fase di validazione sui dati di partenza 3 dei 4 modelli

  3. HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli-Similar 3 (Glis3 Transcriptional Activity.

    Directory of Open Access Journals (Sweden)

    Gary T ZeRuth

    Full Text Available The transcription factor Gli-similar 3 (Glis3 plays a critical role in the generation of pancreatic ß cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases.

  4. The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts.

    Science.gov (United States)

    Vered, M; Peleg, O; Taicher, S; Buchner, A

    2009-08-01

    The aggressive biological behavior of odontogenic keratocysts (OKCs), unlike that of other odontogenic cysts, has argued for its recent re-classification as a neoplasm, 'keratocystic odontogenic tumor'. Identification of mutations in the PTCH gene in some of the OKCs that were expected to produce truncated proteins, resulting in loss of control of the cell cycle, provided additional support for OKCs having a neoplastic nature. We investigated the immunohistochemical expression of the sonic hedgehog (SHH) signaling pathway-related proteins, PTCH, smoothened (SMO) and GLI-1, and of the SHH-induced bcl-2 oncoprotein in a series of primary OKC (pOKC), recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome-associated OKCs (NBCCS-OKCs), and compared them to solid ameloblastomas (SAMs), unicystic ameloblastomas (UAMs), 'orthokeratinized' OKCs (oOKCs), dentigerous cysts (DCs) and radicular cysts (RCs). All studied lesions expressed the SHH pathway-related proteins in a similar pattern. The expression of bcl-2 in OKCs (pOKCs and NBCCS-OKCs) and SAMs was significantly higher than in oOKCs, DCs and RCs (P < 0.001). The present results of the immunoprofile of OKCs (that includes the expression of the SHH-related proteins and the SHH-induced bcl-2 oncoprotein) further support the notion of OKC having a neoplastic nature. As OKCs vary considerably in their biologic behavior, it is suggested that the quality and quantity of interactions between the SHH and other cell cycle regulatory pathways are likely to work synergistically to define the individual phenotype and corresponding biological behavior of this lesion.

  5. Model-free nuclear magnetic resonance study of intermolecular free energy landscapes in liquids with paramagnetic Ln3+ spotlights: theory and application to Arg-Gly-Asp.

    Science.gov (United States)

    Fries, Pascal H

    2012-01-28

    We propose an easily applicable method for investigating the pair distribution function of a lanthanide Ln(3+) complex LnL (L = ligand) with respect to any solvent or solute molecule A carrying observable nuclear spins. Let r be the distance of Ln(3+) to the observed nuclear spin I. We derive a simple expression of the experimental value of the configurational average of 1/r(6) in terms of longitudinal paramagnetic relaxation (rate) enhancements (PREs) of the spin I measured on a standard high-resolution NMR spectrometer and due to well-chosen concentrations of LnL complexes in which Ln(3+) is a fast-relaxing paramagnetic lanthanide or the slowly-relaxing gadolinium Gd(3+). The derivation is justified in the general case of a molecule A which is by turns in a bound state where it follows the complex and a free state where it moves independently. It rests on the expression of the underlying PRE theory in terms of the angle-dependent pair distribution function of LnL and A. The simplifications of this theory in the high-field regime and under the condition of fast exchange between bound and free states are carefully discussed. We also show that original information on the angle dependence of the molecular pair distribution function can be gained from the measured paramagnetic dipolar shifts induced by complexed fast-relaxing Ln(3+) ions. The method is illustrated by the case study of the anionic Lnttha(3-) = [Ln(3+)(ttha)](3-) (ttha(6-) = triethylene tetraamine hexacetate) complex interacting with the biologically important tripeptide Arg-Gly-Asp (RGD) which carries peripheral ionic groups. The usefulness of an auxiliary reference outer sphere probe solute is emphasized. © 2012 American Institute of Physics

  6. Mecanismos involucrados en la promoción de crecimiento axonal por la glia envolvente del bulbo olfatorio

    Directory of Open Access Journals (Sweden)

    Vilma C. Muñetón-Gómez

    2001-06-01

    Full Text Available La actividad que promueve el crecimiento de axones por la glia envolvente (GE del bulbo olfatorio depende de la expresión de diversas moléculas durante el desarrollo, la vida adulta y la reparación de lesiones nerviosas. Diversas moléculas tales como las neurotrofinas y sus receptores, los factores de crecimiento, las moléculas de adhesión celular, las moléculas de matriz extracelular y las moléculas asociadas con la mielinización son producidas por la glia del sistema olfatorio durante el desarrollo. Su expresión sostenida durante la vida adulta parece estar asociada con el reemplazo celular y la alta plasticidad de este sistema. A su vez, su expresión se involucra en procesos de reparación de lesiones mediados por trasplantes de glia. La migración de la GE, que acompaña axones en crecimiento, se observa durante el desarrollo y en procesos de regeneración luego de una lesión. Los trasplantes de,GE permiten la navegación de brotes regenerantes a través del tejido gliótico inhibidor formado luego de una lesión del sistema nervioso central. El propósito de esta revisión es profundizar en los mecanismos de actividad promotora de crecimiento axonal.

  7. Determinantes del ingreso y del gasto corriente de los hogares

    OpenAIRE

    Muñoz C., Manuel

    2004-01-01

    Este ensayo de investigación empírica analiza los determinantes del ingreso y del gasto en los hogares colombianos. Utilizando un modelo del ciclo de vida con datos de la encuesta de hogares de 1994 y 1995, muestra que el comportamiento del ingreso está afectado principalmente por las características demográficas del hogar y los rasgos socio ocupacionales de sus miembros. El comportamiento del gasto está determinado ante todo por el ingreso y, en menor medida, por las características sociales...

  8. Las fluctuaciones del nivel del mar durante el Cuaternario

    OpenAIRE

    Pousa, Jorge Lorenzo; Isla, Federico Ignacio; Schnack, Enrique Jorge

    2002-01-01

    Los cambios del nivel del mar han ejercido una fuerte influencia en la evolución del planeta y en la historia de la humanidad. En una escala de tiempo geológico, las variaciones de los niveles oceánicos han dejado un registro ampliamente distribuido en la forma de depósitos sedimentarios. El descenso del nivel del mar durante la Ultima Glaciación, que alcanzó unos 120 metros hace 18.000 años, permitió la emergencia del estrecho de Bering y la migración humana desde Eurasia hacia América. Se e...

  9. La imagen del pase.

    Directory of Open Access Journals (Sweden)

    Hernando Bernal.

    1999-11-01

    Full Text Available A partir de un texto del poeta Octavio Paz llamado «La imagen», se busca proseguir la equivalencia entre las imágenes de la poesía y la función que ellas tienen para el poeta, y el fantasma fundamental y su función para el analizante que está en el momento del pase. Se parte de la idea de que la poesía busca entrar en el ser así como el psicoanálisis tiene como finalidad apuntar al corazón del ser del sujeto. Se hace entonces una distinción del concepto de «ser» para el psicoanálisis, haciendo alusión también al discurso de la filosofía. Esclarecido el sentido de lo que es el «ser» para el psicoanálisis, se aborda de lleno – entre otras cosas, relacionadas con la experiencia del pase específicamente- la equivalencia entre la definición que hace Octavio Paz de «La Imagen» y el momento del pase en el análisis de un sujeto, imagen que, al igual que el mito para la filosofía, las leyes para la ciencia y el matema para el psicoanálisis, se constituyen en los instrumentos con los que cada una de estas disciplinas horadan en lo real.

  10. Gerberto, gli Arabi e Gerusalemme

    Science.gov (United States)

    Sigismondi, C.

    Gerbert of Aurillac went in Catalonia from 967 to 970, to visit the bishop Atton of Vic, famous for mathematical knowledge, during the apogee of Cordova's reign of the Caliph Al-Hakam II ibn Abd al-Rahman (961-976). He maintained contacts with local personalities like Mirò Bonfill (Bishop of Girona) and Lupitus of Barcelona through letters (both dated 984). When he was pope, Gerbert sent five papal privileges to Catalan dignitaries, showing his attention to this territory. The Caliph's prime minister Al-Mansu'r depredated Barcelona in 985, and conquered Santiago de Compostela in 997, drawing to an end the cultural exchanges between Christian and Arabic world through Mozarabic and Jewish translators. Gerbert learned and after taught and used Indo-Arabic numbers, abaci, astrolabes, monochords and theoretical music. It was possible for pilgrims to reach Jerusalem at Gerbert's times, and a letter written by Gerbert probably for an abbot starting his pilgrimage seems to introduce the first ideas of crusade and indulgences related to offers. The change of attitude of the Al-Andalus' government toward Christianity is probably responsible of these words written in a time very close to the depredations of Barcelona. Jerusalem is also in the index of geographic places in the book of the astrolabe, attributed to Gerbert, as well as Santiago de Compostela. Finally the legend of the Golem and the mass celebrated in the church of Jerusalem in Rome, completes the panorama of Gerbert and the Holy City.

  11. del Estado Aragua

    Directory of Open Access Journals (Sweden)

    Joselys Cintia Zerpa

    2008-01-01

    Full Text Available Diagnostica la situación actual de los bienes que conforman al patrimonio histórico-cultural del Municipio Zamora, Estado Aragua, Venezuela. La Investigación es descriptiva y de campo, comprendió la elaboración de un inventario de los bienes inmuebles, festividades religiosas y manifestaciones artesanales del municipio. Se estudiaron la condición física y uso actual de estos bienes y los planes y proyectos existentes. Analizó el marco normativo que los rige. Se obtuvo la opinión de los representantes de organismos públicos relacionados con la actividad turística del Municipio, de los visitantes, cronistas e historiadores. Aportes: La mayoría de los bienes se encuentran en buen estado de conservación, Las manifestaciones culturales, festividades y la artesanía se desarrollan periódicamente pero no son aprovechadas turísticamente, Se determinó que existe un marco normativo para tales bienes y No existen propuestas actuales referentes a estos bienes. Se reflejó el interés de los sectores institucional y privado para la incorporación de estos bienes a la oferta turística del Municipio y del Estado

  12. APOSTILLAS ACERCA DEL POSTRABAJO

    Directory of Open Access Journals (Sweden)

    Arturo Torrecilla

    2000-01-01

    Full Text Available El más reciente debate en torno al postrabajo transforma la herencia de los dos ciclos que le precedieron desde los años setenta. El primero se correspondía con la crítica de la división social y técnica de labores informada por una filosofía de la alienación o bien por una rectificación de la arquitectónica marxista pero salvaguardando la promesa laborista del buen trabajo. El segundo ciclo hacía eco del rechazo a las cadenas de montaje fordistas y se abría al horizonte de la abolición del trabajo salarial, manteniendo sin embargo el abolengo del sujeto unitario de la historia. La presente escena asume una densidad mayor, producto del encuentro entre las nuevas tecnologías informacionales, las discusiones en el ámbito de la sociología y la antropología, de la tecnología y la ciencia, junto al dueto que inaugura el posmodernismo.

  13. Apostillas acerca del postrabajo

    Directory of Open Access Journals (Sweden)

    Arturo Torrecilla

    2000-04-01

    Full Text Available El más reciente debate en torno al postrabajo transforma la herencia de los dos ciclos que le precedieron desde los años setenta. El primero se correspondía con la crítica de la división social y técnica de labores informada por una filosofía de la alienación o bien por una rectificación de la arquitectónica marxista pero salvaguardando la promesa laborista del buen trabajo. El segundo ciclo hacía eco del rechazo a las cadenas de montaje fordistas y se abría al horizonte de la abolición del trabajo salarial, manteniendo sin embargo el abolengo del sujeto unitario de la historia. La presente escena asume una densidad mayor, producto del encuentro entre las nuevas tecnologías informacionales, las discusiones en el ámbito de la sociología y la antropología, de la tecnología y la ciencia, junto al dueto que inaugura el posmodernismo.

  14. La universidad del futuro

    Directory of Open Access Journals (Sweden)

    FERNANDO SANCÉN CONTRERAS

    2013-01-01

    Full Text Available El trabajo señala la necesidad de reconstruir la Universidad, dado el dinamismo que muestra la ciencia y la sociedad, pues trae consigo cambios sustanciales en la visión del mundo y en el aumento del poder del hombre sobre la naturaleza. Se analizan los supuestos epistemológicos de la universidad tradicional y se propone una nueva explicación del conocimiento humano, enfatizando el conocimiento científico. Postula una docencia fundada en las propiedades de la ciencia, cuyo método inductivo basado en los paradigmas vigentes: analítico, crítico, pragmático, ofrece una herramienta para la docencia, la investigación y la difusión de la cultura. Se propone una educación centrada en el sujeto que se hace a sí mismo (etopoiética y que insiste en el proceso de auto-creación del individuo y de la sociedad.

  15. Significado presente del CSIC

    Directory of Open Access Journals (Sweden)

    Garrido Gallardo, Miguel Angel

    2000-05-01

    Full Text Available Not available

    Este artículo, elaborado en 1999, ofrece una panorámica de la realidad del Consejo Superior de Investigaciones Científicas en la actualidad. Repasa su organización, su volumen de publicaciones, sus indicadores de productividad, su capacidad de obtener recursos y, en suma, su lugar en el conjunto del sistema español de Ciencia y Tecnología, considerado en sí mismo y en relación con la Universidad. Como conclusión del repaso de datos, se afirma que, aunque la fórmula del CSIC, como organismo nacional e interdisciplinario, no es la única posible, la organización del Estado de las Autonomías, así como la evaluación de los datos con que se cuenta, la hacen vivamente recomendable. No hay, pues, sino que seguir con su desarrollo.

  16. Dalt del tren

    Directory of Open Access Journals (Sweden)

    Jaume Subirana

    2001-11-01

    Full Text Available Ens consta que la saviesa popular hi toca més del que a aquest temps d’enquestes, telèfons mòbils i targetes de crèdit li ve de gust admetre, per això em fa gràcia, en veure la pausada però continuada intrusió de la cultura catalana a Internet, recordar les cançons de quan era petit: “Dalt del tren, tots anem-hi dalt del tren, hi ha lloc per tota la gent”, dèiem, i “El tren pinxo de Banyoles és el més bonic que hi ha, ple de llaunes i cassoles i barrets de capellà”. I resulta que per una vegada a la vida hem pujat, efectivament, dalt del tren que passava per l’estació de Catalunya i en cinc anys hem passat de gairebé res a prou pàgines amb un contingut, a més, apreciable i, sobretot, a un petit teixit de persones i institucions que han entès la importància de la revolució comunicativa que Internet representa i que hi teixeixen i projecten webs amb el convenciment dels conversos.

  17. Las carreras del futuro

    Directory of Open Access Journals (Sweden)

    Luis Piscoya Hermoza

    2011-07-01

    Full Text Available La primera década del siglo XXI ha estado signada por un énfasis en los estudiosde prospectiva, los mismos que, a partir de procesos de complejizacióny articulación de la sociedad planetaria como son la digitalización, el progresivodeterioro del medio ambiente, la necesidad del cambio de la matriz energéticay la globalización del mercado, han ensayado hipótesis para identificar lastendencias que se fortalecerán y profundizarán durante las próximas décadas.Desde el punto de vista metodológico, existen muchas maneras de clasificarlaspara conceptualizarlas y entenderlas mejor. Sin embargo, considerando lanaturaleza de esta edición nos proponemos enfocar directamente aquellas queestán estrechamente ligadas a la formación universitaria.Naturalmente, no pensamos que estamos ante tendencias inevitables en lamedida que epistemológicamente la creencia en leyes históricas deterministases insostenible y la práctica social nos muestra que la construcción del futuroes nuestra responsabilidad y siempre rebasa las mejores previsiones.

  18. L'uso del doppiaggio e del sottotitolaggio nell'insegnamento della L2: Il caso della piattaforma ClipFlair

    Directory of Open Access Journals (Sweden)

    Lupe Romero

    2016-01-01

    , where the users can find materials – including activities, clips and tutorials – collaborate through groups, send feedback through forums, etc.   Keywords: foreign learning language; translation; subtitling; dubbing; video.   Riassunto – Lo scopo di questo articolo è quello di presentare il progetto Clipflair, una piattaforma web per l'apprendimento delle lingue straniere (L2 attraverso la risonorizzazione (revoicing e il sottotitolaggio (captioning nei filmati. L’uso di materiale audiovisivo nelle aule di lingua è una pratica frequente per gli insegnanti in quanto introduce varietà linguistiche, mostra elementi culturali non verbali e, ciò che è più importante, presenta aspetti linguistici e culturali della comunicazione nel loro contesto. Tuttavia, gli insegnanti che usano gli audiovisivi hanno la difficoltà di trovare attività che permettano un ruolo attivo degli studenti al di là della semplice visione del film. ClipFlair permette di lavorare con materiale audiovisivo in modo produttivo e anche motivante, chiedendo agli studenti di fare il revoicing  o il sottotitolaggio di un filmato. Revoicing è un termine usato per riferirsi alla risonorizzazione di un filmato, come sarebbe il doppiaggio, il libero commento, l’audiodescrizione o il karaoke. Il termine captioning fa riferimento all’inserimento di un testo scritto sul filmato come nel caso dei sottotitoli convenzionali oppure i commenti o gli intertitoli. I filmati possono essere brevi file di video o audio, compresi i documentari, scene di film, notizie, animazioni e canzoni. ClipFlair sviluppa materiali che permettono agli studenti di lingue straniere di mettere in pratica le quattro abilità basilari del QCER: scrivere, parlare, ascoltare e leggere. Nell’ambito del progetto, sono state elaborate più di 350 attività di doppiaggio e/o sottotitolaggio. Queste attività sono state create per più di 16 lingue tra cui l’inglese, lo spagnolo e l’italiano, ma soprattutto ci sono attivit

  19. Componente Cultura del Agua del PMGRH: plan de trabajo

    OpenAIRE

    Autoridad Nacional del Agua; Proyecto de Modernización de la Gestión de Recursos Hídricos

    2012-01-01

    Describe el plan de trabajo del Componente Cultura del Agua del Proyecto de Modernización de la Gestión de Recursos Hídricos (PMGRH) en relacion a dos aspectos estructurales del proyecto: 1. Mejora de la capacidad de la Gestión Integrada de Recursos Hídricos (GIRH) a nivel nacional y 2. Fortalecimiento de las capacidades de GIRH en las cuencas.

  20. En busca del concepto de gerencia del cuidado

    Directory of Open Access Journals (Sweden)

    Ligia Teresa Mora-Delgado

    2005-12-01

    Full Text Available Este articulo, presenta los conceptos de gerencia del cuidado de enfermería, desarrollado por las enfermeras profesionales que laboran en le Empresa social del estado Hospital Universitario Erasmo Meoz de las Ciudad de Cúcuta, desde su desempeño en la asistencia, administración y docencia. Se pretende además precisar los elementos gerenciales, sociales, humanísticos y éticos que deben hacer parte del concepto de gerencia del cuidado.

  1. LA PERSISTENCIA DEL SUBALTERNO

    Directory of Open Access Journals (Sweden)

    John Beverley

    2002-01-01

    Full Text Available Este trabajo es el texto literal de una ponencia presentada en un panel sobre los estudios culturales latinoamericanos en el congreso de LASA en 2001 en Washington DC. Representa la posición desarrollada en el trabajo colectivo del llamado Grupo de Estudios Subalternos Latinoamericano, desde nuestra fundación en 1992 hasta la disolución del grupo en 2001, que sirve como pretexto introductorio para la ponencia. Los otros participantes en el panel eran Walter Mignolo, representando los estudios poscoloniales, Néstor García Canclini y John Kraniauskas, representando los estudios culturales, y Nelly Richard representando la llamada crítica cultural. El trabajo dialoga y debate con cada una de estas posiciones respectivamente desde el punto de vista específico de los estudios subalternos. Concluye con un llamado a una crítica del saber académico en sí.

  2. Acalasia. Controversias del tratamiento

    OpenAIRE

    Restrepo P, Antonio J; Rey T, Mario H; Garzón O, Martín A; Farfán Q, Yesid A; Molano V, Juan C; Marulanda, Juan C; Lizarazo, Jorge I

    2007-01-01

    La acalasia es un desorden motor del esófago caracterizado por pérdida de la peristalsis esofágica con falta en la relajación o relajación incompleta del esfínter esofágico inferior (EEI) (1). La causa exacta de este trastorno es desconocida. Los síntomas más comunes son disfagia, regurgitación, pérdida de peso y dolor torácico (2). La manometría esofágica es el principal método diagnóstico, mostrando aperistalsis del cuerpo esofágico con aumento de la presión, falta de relajación o relajació...

  3. Procedimiento Del Triple Fin

    Directory of Open Access Journals (Sweden)

    Oscar L. Bellido Aguilera

    2008-01-01

    Full Text Available Presenta un procedimiento novedoso basado en un método dialéctico - sistémico - integrador, que facilita la precisión de los fines u objetivos más generales de un proceso de desarrollo comunitario o de otros procesos de cambio deseados (un proyecto sociocultural, una investigación social, un proceso de mejoramiento organizacional, etc.. Su importancia radica en que los fines, según Marx, son una guía que rige como una ley la actuación del hombre y determinarlos es parte esencial del planeamiento del cambio. Se trata de un asunto aparentemente simple, sin embargo, en la práctica es mucho más problemático de lo que comúnmente se cree.

  4. Efecto del silicio y plaguicidas en la fertilidad del suelo y rendimiento del arroz

    OpenAIRE

    Furcal-Beriguete, Parménides; Herrera-Barrantes, Alejandra

    2013-01-01

    Efecto del silicio y plaguicidas en la fertilidad del suelo y rendimiento del arroz. El objetivo de este trabajo fue evaluar el efecto del silicio en la fertilidad del suelo, la incidencia de enfermedades y plagas insectiles, el rendimiento y la calidad de granos del cultivo de arroz. El estudio se realizó en La Vega, Florencia, San Carlos, Costa Rica entre mayo y octubre en los años 2010 y 2011, en el mismo lote con la variedad CR 4477. Se establecieron cinco tratamientos: silicio al suelo, ...

  5. Storia del pensiero matematico

    CERN Document Server

    Kline, Morris

    1999-01-01

    Costruita con l'intento di presentare le idee oltre ai protagonisti della matematica, questa storia ha il duplice pregio dell'esaustività e della chiarezza. Essa prevede infatti vari livelli di lettura: lo specialista vi trova una messe di dati, fonti e spunti di ricerca, mentre lo studente ha a disposizione un formidabile strumento di consultazione e sintesi. L'arco temporale coperto è vasto: dalla Mesopotamia a Euclide, da Fibonacci all'invenzione del calcolo infinitesimale, da Gauss a Poincare, con un'appendice dedicata agli sviluppi piu recenti scritta appositamente per la prima edizione italiana del 1991, nei «Manuali» Einaudi.

  6. La escritura del quechua

    OpenAIRE

    Authier, Martine du

    2015-01-01

    La mayor fantasía ha acompañado siempre la transcripción del quechua. El primer intento de sistematización fue el sistema de la Paz, en 1953. Sin embargo, no existe en el comercio un diccionario satisfactorio en lo que se refiere al quechua del Cusco y, prácticamente, nada se edita en quechua, fuera de algunos trabajos antropológicos bilingües. Bajo la égida de la UNESCO, la Academia Peruana de la Lengua Quechua, que tiene su sede en el Cusco, ha colaborado en un diccionario de doce de los tr...

  7. El lenguaje del cerebro

    Directory of Open Access Journals (Sweden)

    Antonio Ibáñez Molina

    2011-04-01

    Full Text Available La introducción de nuevas técnicas de análisis de ritmos EEG en estudio de la comprensión del lenguaje permite explorar esta habilidad humana desde una perspectiva de integración de grupos de redes neuronales. Los ritmos de disparo neuronal que generan estos grupos pueden conectarse por sincronía formando unidades funcionales transitorias distribuidas en diversas áreas del cerebro. En esta revisión comentamos algunos de estos ritmos y su relación con el lenguaje.

  8. Plasticidad del sistema nervioso

    Directory of Open Access Journals (Sweden)

    L. M. Garcia-Segura

    1976-06-01

    Full Text Available En este trabajo se revisan los conocimientos más recientes sobre el fenómeno de la plasticidad del sistéma nervioso, tanto a nivel morfológico como a nivel fisiológico y molecular. Se estudian los cambios morfólogicos y fisiológicos de las neuronas frente a la experiencia. Tambien se considera la adaptación molecular del sistéma nervioso a la información que recibe como la base de todo tipo de plasticidad.

  9. Las causas del desempleo

    OpenAIRE

    García Balbás, Salomé

    2014-01-01

    En este documento vamos a tratar de dar respuesta a la siguiente pregunta: ¿cuáles son las causas del desempleo? Para ello realizaremos un repaso de las principales teorías económicas del desempleo llegando a la conclusión de que existe una causa fundamental que lo genera: la rigidez de los salarios a la baja. Consideramos el desempleo como la existencia de un exceso de oferta en el mercado de trabajo y haremos alusión, únicamente, a la existencia de desempleo involuntario. La exposición de l...

  10. Inventario del Archivo del conde de Bornos

    Directory of Open Access Journals (Sweden)

    Pedro Antonio Porras Arboledas

    1995-01-01

    Full Text Available Mi primer contacto con esta Casa se remonta a algunos años atrás, cuando me Mamó la atención un documento muy interesante, publicado a comienzos del presente siglo por el ilustre erudito ubetense don Alfredo Cazaban, por el que los Reyes Católicos hacían merced a su secretario y jefe de la artillería real durante la Guerra contra Granada, Francisco Ramírez de Madrid, personaje madrileño de origen cántabro, de una heredad en término de Jaén —el cortijo de Bornos— por sus grandes esfuerzos en la conquista de las plazas, hasta el momento inexpugnables, de Cambil y Alhabar. Posteriormente, al realizar un estudio sobre el régimen señorial en el Reino de Jaén, intenté localizar los archivos de las diferentes casas nobiliarias asentadas en esta provincia, gracias a lo cual pude saber que la documentación del Condado de Bornos se hallaba en Madrid, bien en la Biblioteca Nacional o en el Archivo Histórico, ya que el actual Conde, el Excmo. Sr. Don Ignacio Ramírez de Haro, así me lo comunicó en marzo de 1983.

  11. Analisi dell'efficacia di un programma di prevenzione secondaria del carcinoma orale

    Directory of Open Access Journals (Sweden)

    S. Iannazzo

    2003-05-01

    Full Text Available

    In Italia i carcinomi del cavo orale (KCO sono diagnosticati
    prevalentemente al II-IV stadio TNM con conseguenti basse sopravvivenza a 5 anni e qualità della vita. Una maggior frequenza di diagnosi allo stadio I porterebbe a migliorare ampiamente i valori medi dei suddetti parametri.
    Scopo del presente lavoro è stato valutare l’efficacia di un programma di prevenzione secondaria del KCO in termini di aumento di diagnosi allo stadio I e di vite salvate.

    Abbiamo stimato la prevalenza di casi istopatologicamente
    accertati (livello C3 di leucoplachia, principale lesione precancerosa del KCO, nella ASL/RMA come prodotto tra la prevalenza stimata di leucoplachia diagnosticata clinicamente (livello C2 (2989,2Ĩ13077,7 e la proporzione, scelta arbitrariamente, di C3 tra i C2 (0,50.

    Tenendo presente che nel campione studiato nella ASL/RMA la proporzione di KCO allo stadio I tra i C3 era 0,03, abbiamo stimato il numero di KCO.

    Abbiamo stimato quanti KCO verrebbero diagnosticati allo stadio I se venisse attuato un programma di prevenzione secondaria, considerando diversi livelli di compliance, e sulla base di una sopravvivenza media a 5 anni, in Italia, del 53% per tutti gli stadi e del 79% per i KCO allo stadio I, abbiamo calcolato il numero di vite salvate. I valori sono stati espressi come IC95.

    Le prevalenze di leucoplachia C3 e KCO sono risultate,
    rispettivamente, 1494,6Ĩ6538,8 e 44,8Ĩ196,2. Con compliance del 10%, 40% e 75% verrebbero diagnosticati, rispettivamente, 4,5Ĩ19,6, 17,9Ĩ78,5 e 33,6Ĩ147,2 casi di KCO e le vite salvate sarebbero 1,1Ĩ5,1, 4,6Ĩ20,4 e 8,7Ĩ38,3 rispettivamente.
    In termini di vite salvate i dati evidenziano la necessita di attuare programmi di screening del KCO, anche nell' eventualità di uno scarso coinvolgimento della popolazione a rischio.

  12. The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

    Directory of Open Access Journals (Sweden)

    Corbett Alastair

    2008-11-01

    Full Text Available Abstract Background We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2-related Parkinson's disease (PD in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S, is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results Thirty-one out of 509 families with multiple cases of PD (6.1% were found to have 58 LRRK2 mutation carriers (6.4%. Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility

  13. Polycystic kidney disease in the medaka (Oryzias latipes pc mutant caused by a mutation in the Gli-Similar3 (glis3 gene.

    Directory of Open Access Journals (Sweden)

    Hisashi Hashimoto

    Full Text Available Polycystic kidney disease (PKD is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3 gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients.

  14. Competencia Desarrollo del Pensamiento Creativo

    OpenAIRE

    Rodríguez, Eric; Miceli, Francisco; Tiburcio, Georgina; Gómez, Orlando

    2012-01-01

    1. ¿Qué significa la competencia Desarrollo del Pensamiento Creativo? 2. ¿Por qué es relevante que adquiera la competencia Desarrollo del Pensamiento Creativo en mi formación? 3. ¿Cómo aprendo la competencia Desarrollo del Pensamiento Creativo? 4. ¿Cómo aplico la competencia Desarrollo del Pensamiento Creativo? 5. ¿Cómo puedo autoevaluar mi competencia (con miras a un constante crecimiento)?

  15. Utopia economica. Uno studio genealogico del neoliberalismo di Gary Becker in relazione al pensiero di Jeremy Bentham

    Directory of Open Access Journals (Sweden)

    Eleonora Buono

    2016-12-01

    Full Text Available L’Autrice si propone di tracciare la genealogia della posizione neoliberale, partendo soprattutto dai testi di Gary Becker. Il pensiero economico neoliberale è posto in relazione con la rivoluzione scientifica e l’operazione di matematizzazione della natura che da essa scaturisce. Questo percorso porterà poi a Jeremy Bentham, il cui sistema è spesso visto come antesignano degli studiosi neoliberali. Secondo la tesi sostenuta dall’Autrice, il neoliberalismo presenta il proprio sguardo come una neutra e scientifica descrizione del reale, sennonché in tale mossa si annida pur sempre una tendenza normativa. È così che gli economisti neoliberali elaborano un sistema che è altresì prescrittivo, proponendo un modello che si pone sul piano politico; modello il quale viene qui designato con il nome di «utopia economica».

  16. Stile didascalico e verità del mito in un exemplum ovidiano : Ars amatoria 1, 623-6

    Directory of Open Access Journals (Sweden)

    Federica Bessone

    2010-11-01

    Full Text Available Nell'Ars amatoria l'uso ironico degli exempla mitologici rientra nella parodia del genere didascalico. Per dimostrare che le blanditiae piacciono anche alle donne caste e vergini, il maestro d'amore ricorda che Giunone e Atena si vergognano “ancora adesso” di non aver vinto il Giudizio di Paride. L'impiego di una formula didascalica lucreziana dà scherzosamente una pretesa di scientificità a un exemplum tratto dal mito, e da un mito spesso contestato per il suo contenuto incredibile e scandaloso. Ovidio dà una risposta polemica alla critica razionalistica del mito espressa nelle Troiane di Euripide: benché disinteressate al matrimonio, anche la sposa di Giove e la dea vergine per scelta dovevano desiderare ardentemente l'elogio della bellezza, essendo soggette come qualsiasi donna ed essere vivente alla legge della vanità universale. La prova viene dal seguito del mito stesso: lo stilema eziologico nunc quoque rimanda al proemio dell'Eneide, dove il giudizio di Paride è una delle motivazioni antiche dell'ira di Giunone, motore del poema. Il rimando al testo nazionale dei Romani garantisce la verità del mito preso a paradigma dal maestro d'amore: per quanto problematico, quel racconto mitico ha una sua realtà indubitabile; l'esistenza dell'Eneide è la prova – poetica – che l'offesa nella vanità è per Giunone una ferita che perdura. Svincolato ormai dalle sue pretese di veridicità, il mito può riaffermare qui, per gli scopi argomentativi del praeceptor amoris, la sua incontestabile verità letteraria ed ‘umana’.

  17. Ruptura del projecte parental i disposició dels preembrions

    OpenAIRE

    Farnós Amorós, Esther

    2010-01-01

    La tesi doctoral "Ruptura del projecte parental i disposició dels preembrions" analitza els efectes del consentiment a les tècniques de reproducció assistida prestat en el marc d'un projecte parental. La tesi ofereix una resposta als conflictes que enfronten exesposos o exconvivents en relació al destí dels preembrions sobrants d'un cicle de fecundació "in vitro" iniciat durant la relació. Aquests conflictes constitueixen un grup de casos al voltant del qual no hi ha solucions legislatives qu...

  18. La equinoterapia en las distintas alteraciones del desarrollo del menor.

    OpenAIRE

    Chamorro González, Mireya

    2015-01-01

    La equinoterapia consiste en la utilización del caballo como un método terapéutico para rehabilitar a personas con discapacidad. Esta terapia es considerada una gran alternativa para aumentar el autoestima de los que sufren algún tipo de discapacidad, también a través de esta terapia se mejora y fortalece el estado emocional, así del mismo modo ayuda a mejorar la manera de desenvolverse en su entorno social. Esta terapia se realiza a través de la trasmisión del calor corporal del caballo, del...

  19. Gestión del riesgo del cambio (segunda parte)

    OpenAIRE

    Zorrilla Salgador, Juan Pablo

    2004-01-01

    Segunda parte del artículo acerca del uso de futuros sobre el tipo de cambio. Esta continuación abarca estrategias, definiciones, metodología y explicaciones sobre todo lo relacionado con el Ratio de cobertura de los futuros y la aparición del riesgo base.Segunda parte del artículo acerca del uso de futuros sobre el tipo de cambio. Esta continuación abarca estrategias, definiciones, metodología y explicaciones sobre todo lo relacionado con el Ratio de cobertura de los futuros y la aparición d...

  20. del's Proof

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 5. Gödel's Proof - Incompleteness Theorems. S M Srivastava. General Article Volume 12 Issue 5 May 2007 pp 71-84. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/012/05/0071-0084. Keywords.

  1. Marketing Mix del Software.

    Directory of Open Access Journals (Sweden)

    Yudith del Carmen Rodríguez Pérez

    2006-03-01

    Por ello, en este trabajo se define el concepto de producto software, se caracteriza al mismo y se exponen sus atributos de calidad. Además, se aborda la mezcla de marketing del software necesaria y diferente a la de otros productos para que este triunfe en el mercado.

  2. Gerencia del servicio

    OpenAIRE

    Nancy Peña Acosta

    1992-01-01

    Estamos en la era de la pirámide invertida donde el cliente es primero por lo que es fundamental incentivar la calidad desde abajo; hacer que el trabajador defina su misión, sienta que es parte de la compañía para que la satisfacción del negocio realizado sea de todos.

  3. El Juego del Juego

    OpenAIRE

    Carvalho, Nazaré Cristina

    2012-01-01

    DUVIGNAUD, Jean. El Juego del Juego. Santafé de Bogotá, Colômbia: Fondo de Cultura Econômica, 1997.The game gameDUVIGNAUD, Jean. The Game Game. Santafé de Bogotá, Colombia: Fondo de Cultura Econômica, 1997

  4. El helor del cuerpo

    OpenAIRE

    Sánchez-Biosca, Vicente

    1992-01-01

    Ensayo sobre las formas clásicas y modernas de la metamorfosis. En esta figura mitológica se advierte de manera privilegiada la entrada del imaginario científico, biológico y genético en el dominio de las construcciones literarias y cinematográficas.

  5. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2014-12-01

    Full Text Available La publicación se centra en temas como: Procesos electorales en México e Italia, se analizan los procesos comunicacionales y sus efectos; las infiltraciones de las agencias de seguridad en la actividad periodística en Europa; la radio y la televisión pública en los EE.UU. Para conocer cómo la prensa enfrenta los problemas críticos entre países, esta el caso de Uruguay y Argentina (discrepancia por la planta de procesamiento de papel y la contaminación del Río de La Plata. Otro artículo refiere la difícil relación entre los medios de comunicación y el gobierno de Chávez en Venezuela. Se aborda el caso brasileño para entender el crecimiento de los Observatorios de Medios; otro sobre el crecimiento del "periodismo confidencial" en la web y la prensa gratuita. Se estudia el impacto de la telenovela "pasión de gavilanes". Para quienes interese la penetración del Internet está: "Usos y competencias del weblog en las corporaciones" más otro sobre la lucha sorda que mantienen los gigantes de la autopista de la información Google y Yahoo.

  6. Punctualizaciones del CERN

    CERN Multimedia

    2002-01-01

    "Viene de la pagina anterior. Puntualizaciones del CERN. La valoracion que me merece la aprobacion en el Consejo de Ministros el 24 de mayo de un acuerdo de colaboracion entre el MCYT y el CERN para el proyecto de neutrinos al Gran Sasso es positiva" (1 page).

  7. Software del sistema osteomioarticular

    Directory of Open Access Journals (Sweden)

    Dianelys León Medina

    2015-06-01

    Full Text Available Introducción: la aplicación en la enseñanza de las Tecnologías de la Informática y las Comunicaciones, es una de las líneas que ha trazado el sistema de salud cubano en estudiantes de las ciencias médicas. La anatomía es una de las ciencias que integra la disciplina de Morfofisiología y para facilitar su comprensión resulta necesario el empleo de recursos y estrategias, entre los que puede figurar un software educativo. Objetivo: diseñar un software sobre la anatomía del sistema osteomioarticular de cabeza y cuello para los estudiantes de primer año de la carrera de Estomatología de Pinar del Río. Material y método: se realizó un estudio cualitativo. Para obtener los resultados se utilizó el método materialista dialéctico. Para la dialéctica del desarrollo del proceso estudiado se utilizaron los métodos teóricos, empíricos, el estudio profundo del tema, tipo de plataforma a utilizar y criterios de los especialistas. Para su procesamiento se utilizaron técnicas estadísticas descriptivas e inferenciales no paramétricas. Resultados: debido a la necesidad de fortalecer en los estudiantes las habilidades en la utilización de las tecnologías de la informática y las comunicaciones, se elaboró el software de la anatomía del sistema osteomioarticular de cabeza y cuello "Aprendiendo anatomía" mediante imágenes, videos y textos. Conclusiones: el software constituye un aporte al proceso enseñanza aprendizaje, el cual facilita el trabajo independiente y autopreparación mediante la interactividad con el contenido, retroalimentación y evaluación utilizando medios de enseñanza modernos, lo cual tributa al modo de actuación del futuro egresado.

  8. Historia deldel = History of Padel

    Directory of Open Access Journals (Sweden)

    Bernardino Javier Sánchez-Alcaraz Martínez

    2013-10-01

    Full Text Available El presente trabajo resume la historia del deporte deldel. Existen dos versiones sobre el origen deldel. La primera versión relaciona los antecedentes deldel con los de otros deportes de raqueta como el tenis o el bádminton, siendo su origen común el jeu de la paume francés. Posteriormente, surgen variantes en Estados Unidos como el Paddle Tennis y el Platform Tennis, siendo versiones reducidas del tenis, pero con elementos muy comunes al pádel actual. La segunda versión, aprobada por la Federación Internacional de Pádel, afirma que este deporte nació en México, en 1969, a través del empresario Enrique Corcuera.--------------------------------------------------------------------This research summarizes the history of paddle sport. There are two versions about the origin of paddle. The first version relates the history of paddle with other racket sports like tennis or badminton, and its common origin of the Jeu de Paume French. Later, in in the United States, appear two sports called Paddle Tennis and Platform Tennis, which are reduced versions of tennis sport, but these have lot of common characteristics with paddle. The second version, approved by the International Padel Federation, said the sport was born in Mexico in 1969, through the businessman Enrique Corcuera.

  9. Le tormentate vicende del lavoro pubblico

    Directory of Open Access Journals (Sweden)

    Alessandro Bellavista

    2013-07-01

    misure sulla riorganizzazione/riduzione del personale contenute in tali provvedimenti, confermando che gli obiettivi di efficienza e di efficacia dell'azione amministrativa necessitano, più che di interventi normativi, di un rinnovamento culturale del settore, ancora lungi dall'essere raggiunto.

  10. Determinantes del ingreso y del gasto corriente de los hogares

    Directory of Open Access Journals (Sweden)

    Muñoz C., Manuel

    2004-06-01

    Full Text Available Este ensayo de investigación empírica analiza los determinantes del ingreso y del gasto en los hogares colombianos. Utilizando un modelo del ciclo de vida con datos de la encuesta de hogares de 1994 y 1995, muestra que el comportamiento del ingreso está afectado principalmente por las características demográficas del hogar y los rasgos socio ocupacionales de sus miembros. El comportamiento del gasto está determinado ante todo por el ingreso y, en menor medida, por las características sociales del hogar y el gasto de otros hogares con características similares. También examina la influencia de la incertidumbre acerca de los ingresos en el gasto de los hogares para comprobar si estos actúan con motivos de precaución.

  11. Valutazione dell'appropriatezza dei ricoveri in un Policlinico Universitario: analisi mediante l'uso comparativo dei sistemi di classificazione isogravitá APR-DRG e Disease Staging e del PRUO

    Directory of Open Access Journals (Sweden)

    M. Volpe

    2003-05-01

    Full Text Available

    Obiettivi: valutare l’appropriatezza organizzativa dei ricoveri effettuati in un Policlinico Universitario attraverso la comparazione di due metodi, dei quali uno basato sui dati della scheda di dimissione ospedaliera ed utilizza, rispettivamente, i sistemi di classificazione iso-gravità APR-DRG e Disease Staging e l’altro sulla revisione delle cartelle cliniche mediante il PRUO.

    Metodi: oggetto di analisi sono i ricoveri ordinari effettuati nell’anno 2001 ed afferenti ai DRG inclusi nella delibera della Giunta Regionale del Lazio 864/2002 che recepisce il D.P.C.M. 29/11/2001 sui livelli essenziali di assistenza.

    Risultati: i risultati evidenziano che le due varianti del
    metodo basato sulla SDO (metodo APPRO mostrano quote di ricoveri inappropriati sovrapponibili rispetto al complesso dei ricoveri oggetto di analisi, ma con differenze anche rilevanti tra APR-DRG e Disease Staging in relazione ai singoli DRG considerati, riconducibili ai diversi algoritmi di attribuzione del livello di severità utilizzati dai due sistemi. L’analisi campionaria effettuata con il metodo PRUO su casi afferenti ai DRG della DGR 864/2002 caratterizzati da livelli di severità minimi evidenzia una proporzione di ricoveri inappropriati superiore a quella determinata tramite i metodi basati sulla SDO. Tale differenza è verosimilmente dovuta al ruolo del valore delle soglie percentuali di accettabilità individuate dalla Regione Lazio per ciascun DRG: le quote di ricoveri che eccedono tali soglie sono considerate inappropriate.

    Conclusioni: sulla base dei risultati ottenuti gli autori
    descrivono gli interventi organizzativi adottati per ottimizzare il contesto di erogazione delle prestazioni
    oggetto di analisi, discutono vantaggi e limiti dei metodi SDO-based e del metodo analitico PRUObased e ne propongono l

  12. La fuga dell’‘Io’ narrativo nel romanzo del dopoguerra spagnolo

    Directory of Open Access Journals (Sweden)

    Rosa Pignataro

    2014-10-01

    Full Text Available Il contributo consiste in una proposta di analisi di alcuni dei romanzi più significativi del dopoguerra spagnolo a partire dagli anni ’40 fino agli anni ’60-’70. Mi soffermo ad analizzare la ‘fuga’ dell’‘Io’ dalla narrazione in La familia de Pascual Duarte e La colmena, di Camilo José Cela, El camino di Miguel Delibes e Volverás a Región di Juan Benet. Il primo dei romanzi in esame è marcato dalla presenza forte ed imperante del yo narrativo di Pascual che rappresenta appieno la rotondità dell’autobiografia. La ‘fuga’, l’allontanamento, la disgregazione fino alla totale rottura del patto narrativo tra autore e lettore comincia a concretizzarsi con un romanzo della decade successiva, El camino, in cui un narratore onnisciente filtra l’esperienza autobiografica attraverso gli occhi dei bambini. Il passo successivo è la moltiplicazione infinita della rappresentazione del sé in un mosaico di voci e personaggi narranti ne La colmena. La fuga dell’‘Io’, poi, trova la piena realizzazione nell’opera benetiana Volverás a Región che stigmatizza il totale anonimato narrativo dato da un narratore onnisciente ma che, infrangendo le regole ‘tradizionali’ della narrazione, introduce il lettore in uno spazio dai contorni indefiniti, labili, opachi dove l’‘Io’ fluttua, rivela ciò che i personaggi dicono e sentono ma, confondendone nomi e vicende, testimonia la condizione di rovina dell’esistenza umana.

  13. Effetti dei blocchi totali del traffico motorizzato sulla concentrazione dei principali inquinamenti atmosferici

    Directory of Open Access Journals (Sweden)

    C. Signorelli

    2003-05-01

    Full Text Available

    Obiettivi: il contenimento degli inquinamenti atmosferici attraverso blocchi parziali e totali dei veicoli circolanti nelle aree critiche è un tema molto dibattuto negli ultimi anni, soprattutto in relazione all’efficacia a breve e medio termine di questi provvedimenti sulla concentrazione degli inquinanti nell’aria. Sulla base dei dati diffusi dall’ARPA della Regione Lombardia sono stati analizzati gli effetti di due blocchi totali del traffico motorizzato, avvenuti in due domeniche dell’inverno 2001-2002, sulle concentrazioni di due inquinanti specifici per il traffico veicolare, il PM10 e il benzene.

    Metodologia: l’analisi è stata condotta in Lombardia considerando i dati ambientali delle tre zone critiche dove sono stati registrati i valori più elevati di inquinanti atmosferici e dove sono stati attuati i blocchi del traffico come misura d’emergenza (Milano, Como e Sempione. Tramite l’elaborazione di alcuni parametri metereologici, di grafici e di dati relativi l’andamento delle medie giornaliere e orarie degli inquinanti considerati è stata, quindi valutata l’efficacia dei blocchi stradali ai fini della diminuzione dell’inquinamento atmosferico.

    Risultati: i risultati ottenuti hanno evidenziato che le concentrazioni di inquinanti subiscono complessivamente un calo nelle ore di blocco del traffico, ma risalgono rapidamente a partire dalle ore successive la conclusione dei blocchi e non subiscono variazioni significative nei giorni successivi. I fattori metereologici (vento e pioggia intensa rivestono grande importanza nel condizionare la concentrazioni di PM10 e benzene.

    Conclusioni: i risultati confermano che i provvedimenti d’emergenza di limitazione del traffico non rappresentano una soluzione definitiva per ridurre complessivamente l’inquinamento atmosferico nelle aree urbane. Risulta, quindi, necessario effettuare

  14. Estudio del CH interestelar

    Science.gov (United States)

    Olano, C.; Lemarchand, G.; Sanz, A. J.; Bava, J. A.

    El objetivo principal de este proyecto consiste en el estudio de la distribución y abundancia del CH en nubes interestelares a través de la observación de las líneas hiperfinas del CH en 3,3 GHz. El CH es una molécula de amplia distribución en el espacio interestelar y una de las pocas especies que han sido observadas tanto con técnicas de radio como ópticas. Desde el punto de vista tecnológico se ha desarrollado un cabezal de receptor que permitirá la realización de observaciones polarimétricas en la frecuencia de 3,3 GHz, con una temperatura del sistema de 60 K y un ancho de banda de 140 MHz, y que será instalado en el foco primario de la antena parabólica del IAR. El cabezal del receptor es capaz de detectar señales polarizadas, separando las componentes de polarización circular derecha e izquierda. Para tal fin el cabezal consta de dos ramas receptoras que amplificarán la señal y la trasladarán a una frecuencia más baja (frecuencia intermedia), permitiendo de esa forma un mejor transporte de la señal a la sala de control para su posterior procesamiento. El receptor además de tener características polarimétricas, podrá ser usado en el continuo y en la línea, utilizando las ventajas observacionales y de procesamiento de señal que actualmente posee el IAR.

  15. La pluridimensionalidad del rol del docente hospitalario

    Directory of Open Access Journals (Sweden)

    Marian Serradas Fonseca

    2015-07-01

    Full Text Available Este trabajo es el fruto de la observación y la investigación en la trayectoria personal y profesional de la autora dedicada a la educación de niños y niñas en situación de enfermedad u hospitalización. El objetivo de este ensayo es intentar definir de manera específica, el papel, tareas y competencias que el profesional del ámbito educativo tiene en la atención educativa hospitalaria; haciendo especial énfasis en la importancia de la formación de este profesional abogándose por una preparación que permita brindar una atención educativa de calidad a los niños y niñas en situación de enfermedad u hospitalizados.

  16. Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

    Directory of Open Access Journals (Sweden)

    Maldonado-Garza Hector J

    2007-04-01

    Full Text Available Abstract Background The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC. The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses. Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. Methods We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS-PCR. Results The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile. The frequencies of mutated alleles (homozygous plus heterozygous were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2 (p = 0.023. Conclusion This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.

  17. Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome

    DEFF Research Database (Denmark)

    Ambye, Louise; Rasmussen, Susanne; Fenger, Mogens

    2005-01-01

    related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program -- Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele...... and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1alpha gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects...

  18. Formare gli psicologi dell’emergenza all’intervento psicologico in ricerca di dispersi e al sostegno delle famiglie di persone scomparse1. L’esperienza del laboratorio al 5° Campo Scuola di Marco di Rovereto

    Directory of Open Access Journals (Sweden)

    Rina Maria Galeaz

    2012-03-01

    Full Text Available On the occasion of the 5th training camp for the volunteer psychologists of the Civil Protection, it was proposed the workshop “Psychological interventions in search and rescue operations”, managed by experts in support to the aid networks. The aim was to integrate, for the first time, the topic of psychological support to relatives and search and rescue personnel with that of missing persons' families. This experience allowed to develop some reflections about emergency psychologists' training and the intervention models for the dissemination of good practices and the sharing of know-hows with other emergency professionals.

  19. P. Giulierini, P. Bruschetti, F. Gaultier, L. Haumesser, Gli Etruschi dall’Arno al Tevere, Le collezioni del Louvre a Cortona

    OpenAIRE

    Joncheray, Claire

    2018-01-01

    Dans le contexte d’un passage de la valorisation du patrimoine culturel de l’État italien à la municipalité de Cortone (Province d’Arezzo), le Museo dell’Accademia Etrusca e della città di Cortona (ci-après MAEC) s’investit dans une politique de collaboration internationale : il proposait en 2008 une exposition sur les chefs-d’œuvre d’art étrusque conservés au musée de Saint-Pétersbourg, et il propose en 2011 d’accueillir ceux du Louvre au Palazzo Cas...

  20. Climatic change in Italy paste climatic reconstruction; Andamento del clima in Italia negli ultimi cinquanta anni

    Energy Technology Data Exchange (ETDEWEB)

    Colacino, M. [Consiglio Nazionale delle Ricerche, Istituto di Fisica dell' Atmosfera, Rome (Italy)

    2001-06-01

    In the study of the climatic change tied to the anthropogenic enhancement of the greenhouse effect, a very important topic is represented by the past climate reconstruction. This because the analysis of the past variations can help in order to better understand the present trends. With this aim a research on the climatic trends in Italy has been carried out considering the main meteorological parameters. The obtained results indicate that the climate has been subject to a noticeable evolution even if, due to reduced amplitude of the variations, it is not possible to state without any doubt that it is a real climatic change. The present patterns can in fact be connected to the natural climatic variability. [Italian] Nello studio dei cambiamenti climatici legati al potenziamento antropico dell'effetto serra, un ruolo importante riveste la ricostruzione dei climi del passato, poiche' l'analisi delle variazioni passate puo' aiutare a capire meglio gli andamenti attuali. In questa prospettiva, e' stato effetuata una indagine sull'andamento del clima in Italia nel secondo dopoguerra prendendo in considerazione i principali parametri meteorologici. I risultati ottenuti indicano che il clima ha subito una consistente evoluzione, anche se l'ampiezza delle variazioni non consente di affermare che si e' di fronte ad un vero e proprio cambiamento.

  1. Il concetto di sicurezza e la sua percezione. Gli studenti universitari si interrogano/Le concept de sécurité et sa perception. Les étudiants universitaires s'interrogent/Security concept and its perception. Questionnaire for University students

    Directory of Open Access Journals (Sweden)

    Anastasia Moschi

    2013-12-01

    Full Text Available Nell’articolo vengono evidenziati i risultati emersi da una ricerca, concernente la percezione della sicurezza, condotta tra gli studenti universitari nell’anno 2012. Obiettivo dell’indagine era quello di cogliere se, e come, l’appartenenza a corsi di laurea differenti potesse incidere sul modo di trattare e considerare la “questione sicurezza”. Sono emerse, effettivamente, differenze rilevanti nell’approccio al tema in questione declinato nelle sue componenti principali (paura del crimine, vittimizzazione reale e potenziale, interventi auspicabili, preoccupazioni, ruoli istituzionali e dei cittadini. Al contempo però appare evidente anche la necessità che tutti i percorsi universitari e tutti gli attori sociali, anche se da prospettive differenti, si confrontino con il fenomeno-sicurezza per sviluppare una collaborazione tra professionalità diverse che possa condurre verso una cultura della sicurezza. Cet article récapitule les principaux résultats obtenus par une enquête sur la perception de la sécurité menée auprès d’étudiants universitaires en 2012. La présente étude avait pour but d’examiner si le fait d’être inscrit à des cours differents et à différents niveaux pourrait influencer les ideés des étudiants à propos des questions en matière de sécurité. En fait, beaucoup de différences significatives liées à ce sujet ont été remarquées, tels que la peur de la criminalité, le risque réel et potentiel d’être victime de crimes, les mesures d’intervention à envisager, les rôles des institutions et des citoyens. En même temps, l’enquête a souligné la necessité pour les étudiants inscrits à tous les cours et pour tous les acteurs sociaux de se rapprocher au phénomène de la sécurité dans le but de développer la coopération entre différents professionnels en vue d’élaborer une culture commune de la sécurité. This article shows the results of a survey about the perception

  2. ABC del Ajedrez. I

    Directory of Open Access Journals (Sweden)

    Marisel Piñeiro Gomez

    2009-03-01

    Full Text Available La promoción del Ajedrez, su conocimiento y práctica por la población constituye uno de los programas de la Revolución, por tal motivo el presente trabajo está encaminado a proponer un material bibliográfico con variadas posiciones sobre el movimiento-captura de las piezas y los sistemas de notación para los masificadores de Ajedrez del municipio Pinar del Río. En esta investigación se utilizaron variados métodos: teóricos, empíricos y estadísticos, además, como método rector el dialéctico materialista. Constituye una novedad científica porque aporta un material bibliográfico que contiene: la composición,  disposición  e  identificación  del  tablero de  ajedrez;  identificación, colocación, movimiento y captura de las piezas de ajedrez; la promoción del Peón; el valor absoluto de las piezas; los sistemas de notación: descriptivo y algebraico. Se le incluyen más de trescientos gráficos, conceptos que son trabajados de lo simple a lo complejo de manera tal que el masificador de Ajedrez lo utilice en sus clases donde se viabilice el conocimiento gracias a las facilidades que le aporta el material; ofrece algoritmos que le guiarán a elaborar nuevas posiciones, los cuales son inexistentes para este propósito en otras bibliografías; su significación práctica radica en que proporciona, tanto al estudiantado como profesorado, ejercicios de ajedrez sencillos que les permitirá a los primeros para que les sirva en su comportamiento, y a los segundos utilizarlos en su auto preparación; el interés social se halla en que pueden ser utilizados por profesores, personal de apoyo a la docencia,  técnicos  del  INDER,  familiares  de  los  estudiantes  para  ayudarlos;  el interés educativo reside en que a través de esos ejercicios contribuimos al fortalecimiento de valores.

  3. Conversioni mitobiografiche: l’esperienza del mondo nella narrazione di sé e dell’altro

    Directory of Open Access Journals (Sweden)

    Orazio Maria Valastro

    2011-04-01

    Full Text Available L’autobiografia come processo di evocazione e messa in scena della vita (bíos nel movimento della scrittura (gráphein che prende forma a partire da noi stessi (autos, è desiderio di creazione (poiein di sé (autos, processo di creazione di ordine mitobiografico. Proponendo questa definizione per collegare il movimento della scrittura di sé con il processo di creazione di sé, vorrei ricordare il celebre motto inciso sul tempio dell’Oracolo di Delfi: “In te si trova occulto il tesoro degli Dei. Oh Uomo, conosci te stesso e conoscerai l’Universo e gli Dei”. Valorizzando il movimento vitale della vita degli individui attraverso le biografie dell’antica Grecia, l’arte della maieutica manifesta una conoscenza che dispiega l’individuo nella coscienza del mondo e delle sue divinità. Questa riflessione ci permette di considerare le scritture di persone ordinarie come organizzazione metaforica del movimento della scrittura di sé, un movimento che instaura una coscienza mitica nell’organizzazione omologica di pensieri e sentimenti che ci rivelano il flusso del fondo dell’immaginario di un’epoca che prende forma.

  4. Arco del milenio

    Directory of Open Access Journals (Sweden)

    Adell, Josep Mª

    2005-02-01

    the most significant stages in the erection of the Millennium Arch outside the Palacio de Congresos, venue for the 12th IBMAC.
    These pictures are divided into six chapters: Background, Components, Springline, Piers, Arch, Centring Erection and Removal, and Trimming.

    A lo largo de la historia, el Arco de fábrica ha sido el componente constructivo más característico de la Arquitectura y la Ingeniería desde que después de sus inicios etruscos en la época romana fuera desarrollado adelantándose con ello a la cultura helénica.
    El Arco, desde entonces, viene empleándose como una solución constructiva eficiente para cubrir espacios con materiales que no soportan tracciones. La originalidad técnica del Arco lo ha llevado a imponerse como símbolo de las hazañas bélicas como era el Arco de Triunfo.
    En el cambio de siglo y milenio en el que nos encontramos, un salto técnico fundamental se desvela en este Congreso, el Sistema de Albañilería Integral, que abre la posibilidad de ampliar el campo de aplicación de la albañilería con la incorporación del acero, a través de las perforaciones de las piezas, lográndose por fin armar en las tres direcciones del espacio cualquier muro de fábrica que se desee.
    El Arco del Milenio conmemoró el 12th IBMAC de Madrid, mostrando en él los avances técnicos que el Sistema de Albañilería Integral permite, al tratarse de un arco inclinado en el espacio y, por tanto, el primer arco de fábrica construido fuera de la vertical, mediante fábrica de Ladriflor aparejada a tizón, reforzada con barras y cercos.
    El Arco del Milenio, diseñado por J.M. Adell (Presidente del 12th IBMAC, parte de un cilindro de 14 m de diámetro, inclinado 30º sobre el terreno, y construido con fábrica de ladrillo de un pie de grueso, alternando una hilada de color amarillo de cada seis en rojo. El hueco deja un paso libre de 10 m de lado y 5,5 m de altura. La fábrica está armada regularmente por tendeles con cerchas cada

  5. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-11-15

    Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture

  6. Determinantes del trabajo infantil y la escolaridad: el caso del Valle del Cauca en Colombia

    Directory of Open Access Journals (Sweden)

    Sebastián Urueña Abadía

    2009-10-01

    Full Text Available Colombia, al igual que la mayoría de países latinoamericanos, consciente de las repercusiones sociales y económicas negativas del trabajo infantil, se ha comprometido en la lucha por la erradicación de este fenómeno. Prueba de ello es la ratificación por parte del gobierno colombiano en el año 2007, del Convenio 182 de la OIT sobre la Prohibición de las Peores Formas de Trabajo Infantil y la Acción Inmediata para su Eliminación. En el plano regional, como parte del Plan de Desarrollo del Departamento del Valle del Cauca 2008-2011, se está implementando actualmente una estrategia territorial de erradicación del trabajo infantil en sus 42 municipios. Considerando este panorama, este trabajo indaga cuáles son los determinantes del trabajo infantil y la escolaridad en el departamento del Valle a partir de los datos de la Encuesta Nacional de Calidad de Vida del año 2003. Para el análisis se emplea un modelo econométrico Probit Bivariado, que permite el estudio conjunto e interrelacionado de decisiones diferentes, en este caso la asistencia escolar y el trabajo.

  7. En defensa del indigenismo

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Huamán

    2011-05-01

    Full Text Available El indigenismo como movimiento literario, cultural, ideológico y políticoconstituye un hito, una referencia obligada de nuestra tradición culturaly literaria nacional. Su debate no se reduce ni limita a las primerasdécadas del siglo XX, etapa privilegiada en forma recurrente en los estudiosiniciales sobre esta corriente. Podemos afirmar, sin temor a equivocarnos,que no hay momento ni periodo, más o menos visible, en elque no se haya evaluado en forma crítica este acontecimiento, el mismoque ha resurgido con otras denominaciones o referencias (regionalismo,andinismo, mariateguismo, humalismo, etc., a lo largo de nuestro procesohistórico, pero imbuidas de la perspectiva inicial. El propósito deeste artículo es hacer una defensa del indigenismo contestando algunasposiciones contrarias como la de Mirko Lauer.

  8. RESPONSABILIDAD DEL ODONTOPEDIATRA

    OpenAIRE

    Guillen B., Celso

    2014-01-01

    La Responsabilidad de la atención del niño, requiere de una formación y preparación universitaria de la Segunda Especialidad en Odontopediatría para manejar organismos en proceso de crecimiento somático y psicológico. Es por eso que con el proceso de la ciencia se ha comprendido la importancia de la atención del niño desde que nace. Es así que se ha creado sistemas integrales de atención odontopediátrica durante los primeros años de vida, debido a la alta vulnerabilidad de contraer las enferm...

  9. Responsabilidad Constitucional del Gobierno

    Directory of Open Access Journals (Sweden)

    Francisco Zúñiga Urbina

    2006-01-01

    Full Text Available El artículo analiza la responsabilidad constitucional del Gobierno y sostiene que es jurídico-política, de lejano cuño penal y administrativo, y el procedimiento empleado para hacerla efectiva es la acusación en juicio político, que es un típico caso de "justicia política". A la responsabilidad constitucional se suman las responsabilidades civil y penal de Derecho Público del Presidente de la República y sus ministrosThis paper analyses constitutional responsibility of the government and sustains that it is political and juridical, of distant penal and administrative inspiration, and that the procedure used for persecution is impeachment in political trials, demonstrating a typical case of "political justice." Added to the constitutional responsibility of the government are the civil and penal responsibilities of the President and minister's public law

  10. Infecciones del tracto urinario

    Directory of Open Access Journals (Sweden)

    K. Andrés Wurgaft, Dr.

    2010-07-01

    Full Text Available La infección del tracto urinario (ITU, con sus múltiples presentaciones clínicas, está entre las enfermedades infecciosas más frecuentes, tanto en pacientes ambulatorios como hospitalizados. El uso del examen de orina completa y de urocultivo debe ser racional. La bacteriuria asintomática no debe ser buscada ni tratada, en parte porque esto favorece el desarrollo de bacterias resistentes a antibióticos. Distintos cuadros clínicos requieren de distintas duraciones de terapia antibiótica, y tanto el exceso de días de tratamiento como su falta deben evitarse. Se requiere investigación en la búsqueda de estrategias más efectivas para prevenir las ITU recurrentes y en el desarrollo de nuevos antibióticos orales para las ITU resistentes.

  11. Las cruces del olvido

    Directory of Open Access Journals (Sweden)

    Carla Fernandes

    2012-08-01

    Full Text Available Les tragiques événements du « mars paraguayen » ont signifié la disparition de l’espoir en la transition démocratique dans laquelle le pays s’était engagé depuis presque une dizaine d’années. Renée Ferrer, poète, dramaturge, auteur de plusieurs recueils de contes et de deux romans, consigne alors le témoignage poétique de ce drame national dans le recueil Las cruces del olvido (2001. Elle a auparavant publié d’autres textes qui peuvent rentrer dans la catégorie de la poésie sociale : c’est le cas en particulier de Viaje a destiempo (1989 dédié aux victimes de la dictature. Las cruces del olvido, dès son paratexte, insiste sur la fonction de témoignage que l’auteur souhaite assigner à ses vers et sur le rôle que ceux-ci peuvent jouer dans la transmission d’une mémoire collective. La voix d’un jeune disparu de ce « mars paraguayen », le dédoublement qu’il subit et travers lequel il évoque son entrée dans la mort et son absence du monde des vivants, rendent possible l’écriture de cette expérience de l’indicible qu’est la disparition.Los trágicos acontecimientos del «marzo paraguayo» significaron la desaparición de la esperanza en la transición democrática que el país está viviendo desde unos diez años. Renée Ferrer, poeta, dramaturga, autora de varios libros de cuentos y de dos novelas, escribe entonces el testimonio poético de ese drama nacional en su poemario Las cruces del olvido (2001. Ya había publicado antes textos que se pueden considerar como poesía social: es el caso de Viaje a destiempo (1989 dedicado a las víctimas de la dictadura. Desde el texto apertural, Las cruces del olvido potencia la función de testimonio que la autora desea conceder a sus versos y el papel que éstos pueden desempeñar en la transmisión de una memoria colectiva. La voz de un joven desaparecido del «marzo paraguayo», el desdoblamiento que sufre y a través del cual evoca su entrada en la

  12. Carta del editor

    Directory of Open Access Journals (Sweden)

    José Sánchez Gutiérrez

    2018-01-01

    Full Text Available La comunicación científica en México vive enormes retos ante la carrera de adaptar sus formas de comunicación a las nuevas tecnologías. No es tarea fácil convencerse de abandonar el papel y la imprenta para apostar por el código abierto. Sin embargo, esto es apremiante debido al retraso que se lleva en comparación con otras regiones.  Un reto muy evidente ha sido comprender el acceso abierto, reconociendo que este permite mayor visibilidad a la ciencia y que ayuda a evitar el plagio.  Razón por la que nos alegra que a partir del número 37, Mercados y Negocios cuenta con el ISSN electrónico, además del impreso

  13. Carta del Editor

    OpenAIRE

    Luis Eladio Proaño

    2015-01-01

    Henos aquí con un nuevo número de RIESED. Después de casi un año de ver la luz, y como lo anticipábamos en la carta del editor que acompañaba al número fundacional, hacer una revista electrónica no ha sido una tarea sencilla. Un año más tarde no podemos sino confirmar esa opinión.Gracias al decidido trabajo de los autores, revisores y miembros del equipo editorial hemos podido hacerlo. El proceso de revisión de los artículos ha merecido un cuidado, dedicación y tiempo especiales, que hicieron...

  14. Sonidos del Silencio

    Directory of Open Access Journals (Sweden)

    Luz Rodríguez Carranza

    2009-12-01

    Full Text Available La novela ha muerto, afirmaba Alberto Moravia, popularizada, anexada y banalizada por el cine, la televisión, la prensa, la sicología y la sociología. Para Carlos Fuentes en cambio - quien cita a Moravia en 1969 – « lo que ha muerto es sólo la forma burguesa de la novela, el realismo » (17. Basta un viaje rápido por la red para verificar, sin embargo, que la víctima goza de buena salud y que no está confinada en la cultura de masas o en las ciencias sociales : el modelo realista del siglo XIX – y particularmente la creación de tipos representativos de una época, sean éstos promediales o excepcionales - constituye aún la principal preocupación de los escritores y críticos literarios del siglo XXI.

  15. del consumidor mexicano

    Directory of Open Access Journals (Sweden)

    Nadia Huitzilin Jiménez Torres

    2013-01-01

    Full Text Available Pese a que el 80% de la población del mundo vive en mercados emergentes y países en desarrollo, como México, la investigación sobre el consumidor de estos países ha sido insuficiente. El objetivo de este estudio es determinar el perfil del consumidor mexicano en función de variables psicosociológicas como el etnocentrismo, la apertura cultural, el patriotismo, el colectivismo y las características demográficas. Con este propósito se recogió la información de una muestra de 274 consumidores, se realizaron un análisis factorial de sus principales componentes y un análisis cluster con el cual se aglomeró a los individuos en tres grupos con diferentes perfiles psicosociológicos y demográficos.

  16. del noroeste murciano

    Directory of Open Access Journals (Sweden)

    Ma. Luz Tudela Serrano

    2006-01-01

    Full Text Available En la Región de Murcia se está realizando un esfuerzo por aumentar la producción de energías renovables en cumplimiento de los objetivos de Kyoto establecidos para España. Paralelamente, la percepción social acerca de las mismas preocupa cada vez más. En este trabajo, los ciudadanos opinan ante la necesidad de promover el uso e implantación de energías renovables en varias poblaciones afectadas del noroeste. Emplazamientos idóneos, la conservación de los valores naturales y paisajísticos del entorno y las necesidades socioeconómicas de la zona se suman a un uso racional de estas energías y un desarrollo tecnológico paralelo para alcanzar un desarrollo sostenible.

  17. Lo siniestro del enigma.

    Directory of Open Access Journals (Sweden)

    Victoria Eugenia Diaz.

    1999-11-01

    Full Text Available En "El nacimiento de la filosofía griega", Giorgio Colli nos muestra una faceta tenebrosa del enigma. El dios Apolo, de naturaleza ilimitada, insondable, caprichosa, plantea al hombre enigmas que lo enfrentan con el sufrimiento y con la muerte. Allí, Edipo se confronta con enigmas enviados por el dios en los que se pone en juego su propia existencia. Tiempo después, en el transcurrir del siglo XX, reaparece una nueva forma de este dios arbitrario y arrogante: el desaparecedor de personas, ese inmoderado que impone moderación, borra con su acto un cuerpo, una imagen, un nombre, y formula un nuevo enigma siniestro que enfrenta otra vez al hombre con el dolor y con la muerte.

  18. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available El aparecimiento del periodista digital y la educación superior en su formación, el cine indígena y la resistencia cultural, más los Grammy latinos, son temas protagónicos de este número. Se suman la prensa en el combate de piráticas corruptas, los errores de la comunicación del presidente URIBE en el referendo, el fútbol y las Relaciones Públicas en España, la libertad de prensa encarcelada, el Internet y la sociedad de la Información y México: profesiones emergentes para los comunicadores, completan la edición.

  19. Percepcion multisensorial del sabor

    Directory of Open Access Journals (Sweden)

    Charles Spence

    2010-12-01

    Full Text Available La investigación sobre la integración multisensorial de los estímulos auditivos, visuales y táctiles nos está ayudando a entender el funcionamiento de la percepción del sabor. Este conocimiento está teniendo ya un impacto sobre el diseño de alimentos y bebidas, desde los productos que compramos en un supermercado hasta aquellos que encontramos en los restaurantes con estrellas Michelin.

  20. Estado Nutricional del Yodo.

    Directory of Open Access Journals (Sweden)

    Hernando Vargas Uricoechea

    2015-06-01

    Full Text Available INTRODUCCIÓN: Los Desórdenes por Deficiencia de Yodo son un problema serio de salud pública, con cerca de 2 mil millones de personas a riesgo de padecerlos, pudiendo causar bocio neonatal, cretinismo, retardo mental, hipotiroidismo, entre otros. Estos desórdenes son aún prevalentes, y en algunos casos los esfuerzos para su erradicación se han traducido en aumento del riesgo de exceso poblacional de yodo y autoinmunidad tiroidea. En Colombia, se desconoce el estado real de yodo en la población. OBJETIVOS: Determinar la mediana de la yoduría en población escolar, y de los hábitos del consumo de sal, función y parámetros de autoinmunidad tiroidea, y cociente intelectual. MATERIALES Y MÉTODOS: Estudio basado en la comunidad, de corte transversal. Se evaluaron las variables sociodemográficas, la frecuencia de bocio y los niveles de TSH, anti-TPO, anti-Tg, anti-TSHR, yoduria, test de factor G de Cattell, y hábitos del consumo de sal. RESULTADOS: El consumo de sal promedio persona/día fue de 18,13 g. El 37,9% presentó bocio. 36,1% tenían un valor límite en el cociente intelectual. La mediana de yoduria fue de 510,3 μg/L. El 42,75% tuvo anti-TPO positivos, y el 2,87% anti-Tg positivos. El 10% presentó niveles de TSH elevados. CONCLUSIÓN: En escolares de zona urbana, hay un exceso en la mediana de yoduria, pudiendo explicarse por el alto consumo de sal. La alta prevalencia de autoinmunidad tiroidea y bocio, junto al alto nivel de la TSH, puede ser consecuencia del exceso en la ingesta de sal y de otros factores medioambientales/ hereditarios.

  1. El lenguaje del pensamiento

    Directory of Open Access Journals (Sweden)

    Alberto Andreu Marín

    2017-09-01

    Full Text Available ¿Somos capaces de interpretar las señales eléctricas que genera nuestro cerebro cuando estamos pensando? Lo que a priori parece ciencia ficción comienza a ser factible gracias a los avances recientes en técnicas de registro cerebral y en aprendizaje automático. Nos encontramos en el inicio de una nueva era en lo que al conocimiento del cerebro se refiere.

  2. Fundamentos del saber administrativo

    OpenAIRE

    Paola Podestá Correa; Juan Carlos Jurado Jurado

    2005-01-01

    El presente texto tiene por objetivo delimitar, de manera general, algunos de los conceptos más importantes del saber administrativo; en primera instancia, práctica administrativa y saber administrativo. Estos conceptos están ligados con los que en el texto se denominan fundamentos de la administración, estableciendo consensos sobre algunas expresiones comunes en el lenguaje administrativo, y contribuyendo a la comprensión de estos temas para los estudiantes de los primeros niv...

  3. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Jorge Aguirre

    2015-01-01

    Full Text Available La crisis de la prensa Argentina a efecto del mal manejo de la economía y las finanzas, ocupa el tema central. Pasa revista a tres temas de actualidad: El aumento de cobertura y difusión de la prensa gratuita; los esfuerzos de los "viejos" diarios por cambiar de apariencia y el caso del diario estadounidense TODAY que hace veinte años dio un cambio revolucionario en la forma de hacer periodismo diario. Se analizan también temas como: el "carisma" de los líderes actuales, los acuerdos entre los medios de comunicación y el gobierno de México para la difusión de planes y programas oficiales y el rol de los medios en el proceso de establecimiento del ALCA. Agrega el tema controversial sobre la Ley de radiodifusión privada, vigente desde la época de la dictadura pinochetista. En este mismo campo de la Radio otro artículo señala las normas para "contar las noticias" con impacto e interés.

  4. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Jorge Mantilla Jarrín

    2015-01-01

    Full Text Available En este número, el módulo Dibujos Animados, recoge las experiencias del primer curso realizado por el CIESPAL con apoyo de la UNICEF sobre la producción de programas educativos y culturales que utilizan este recurso como una opción comunicacional. Se trata de nuevas tecnologías aprovechadas en Cuba y que pueden ser aplicadas en nuestros países. El módulo relativo al medio ambiente habla del periodismo ecológico con importante desarrollo en América Latina, tema de actualidad que requiere preocupación por parte de los medios de comunicación. Incluye entrevistas a Gunter Grass y Jesús Polanco. Gabriel Alba adentra a los lectores en una novedosa forma de usar las computadoras. En el módulo Debate se trata la Economía, cultura y comunicación; La publicidad vía televisión, La evolución del merchandising en las novelas brasileñas ¿Exigir Ética solo al periodista?

  5. Los felinos del canciller

    Directory of Open Access Journals (Sweden)

    Marco Palacios

    1988-01-01

    Full Text Available En la introducción a una de las obras más influyentes de la historiografía colombiana de nuestros tiempos, el autor, Luis Ospina Vásquez, advierte ciertas dificultades inherentes al oficio de historiar la economía: "Otros aspectos del tema son difíciles de tratar por otros motivos: no se puede citar, entre las causas del difícil adelanto económico de cierta región nuestra, llamada por la generosidad de la naturaleza a una gran riqueza; el hecho de que en ella la política se haya reducido con frecuencia a una pugna entre grupos de hampones[...] Y en el supuesto de que se pudiera dar tratamiento adecuado a lo que, al fin y al cabo, es cosa tangible, no muy difícil de percibir y de describir, faltaría aun dar entrada a un elemento sumamente importante, pero este sí difícil de captar y de transmitir: la 'atmósfera', las 'atmósferas' sucesivas del país y sus regiones, elemento esencial en la historia de la evolución económica.

  6. El Museo del Oro

    Directory of Open Access Journals (Sweden)

    Efraín Sánchez Cabra

    2003-09-01

    Full Text Available El 22 de diciembre de 1939 el Banco de la República compró un objeto de oro de 777,7 gramos de peso y 23,5 centímetros de altura que dio origen al Museo del Oro. Era un poporo quimbaya, pieza maestra de la orfebrería prehispánica. Un objeto bello bello que levanta su bruñido vientre globular y su cuello coronado por cuatro cuerpos esféricos sobre una exquisita base de filigrana fundida, y parece flotar en un espacio propio. Quien lo contempla no puede menos que asombrarse, deleitarse y sentir admiración por sus artífices. Detrás de la compra del poporo había una clara preocupación oficial por proteger una riqueza que comenzaba a entenderse como parte del patrimonio nacional. Esta motivación se pone de manifiesto en una serie de documentos relativos a su adquisición.

  7. Llanto del adulto

    Directory of Open Access Journals (Sweden)

    Alegría Majluf

    2013-09-01

    Full Text Available Se presentan los resultados de un primer estudio transcultural del llanto del adulto que comprende 30 países, entre los que se encuentra el Perú. Vingerhoets et al. (1997 de la Universidad de Tilburg, Holanda, analizan las causas, tendencia y frecuencia del llanto, emociones y sentimientos que inducen al llanto, diferencias y similitudes entre los países y los sexos. Los autores encuentran que las mujeres tienden a llorar con más frecuencia e intensidad que los varones, advirtiendo que en algunos países las mujeres establecen mayor relación entre la tendencia al llanto y el ciclo menstrual que en otros. The results of a first cross-cultural study on adult crying in 30 countries including Peru are presented. Vingerhoets et al. (1997 from the University of Tilburg have analyzed motives, tendencies and frequency of crying, emotions and feelings that provoke crying, as well as differences and similarities among countries and sexes. Results show that women have a tendency to cry more frequently and intensively than men. It has also been noted that, in certain countries, there is a link between crying in women and their monthly period.

  8. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available Artículo de fondo es un ejemplo de una campaña exitosa de Relaciones Públicas realizada para rescatar a Medellín para el turismo, ahora herida de muerte por el narcotráfico. Reinicia el tema sobre el cine, recordando el aniversario del nacimiento de Luis Buñuel. Y sobre el Nuevo Orden Internacional de la Información, Luis Ramiro Beltrán da respuesta a las múltiples interrogantes planteadas en la controversia surgida alrededor del tema. Se da a conocer cómo era el periódico de ayer, de hoy y del futuro frente al desafío de las nuevas tecnologías. Se señala el camino para hacer publicidad en Internet. El Internet y la radio nuevos actores para un mismo mercado. Y para los interesados en la investigación se trata cómo y cuándo hacer sondeos flash y se cierra con el lenguaje periodístico cuándo el dequeísmo es lícito.

  9. comportamiento del consumidor

    Directory of Open Access Journals (Sweden)

    Erico Rentería Pérez

    2006-01-01

    Full Text Available En este artículo se analiza el posicionamiento exitoso de los profesionales, particularmente los jóvenes, a partir de las nuevas realidades del mundo y del mercado laboral, así como la empleabilidad como constructo, estrategias posibles y, finalmente, una discusión sobre falacias y realidades de discursos sobre mercado de trabajo profesional. La reflexión se liga a dos investigaciones, y a redes de discusión en Brasil y Colombia, que reflexionan sobre las implicaciones y requerimientos estratégicos que marcan el ingreso o permanencia en el mercado de trabajo de profesionales jóvenes, y se reconoce que esto afecta a otros tipos de profesionales. La investigación de Rentería (2006ª sobre Empleabilidad arroja información sobre las dos primeras partes. La de Enríquez y Rentería (2006 sobre Estrategias de aprendizaje y empleabilidad informa sobre la tercera. Apoyan la discusión elementos de psicología y comportamiento del consumidor. Se discute la inclusión social y calidad de vida por el trabajo.

  10. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available Abre la revista una retrospectiva de la crisis económica, política y social en la que se precipitó Argentina (2001-2002 y el tratamiento que dieron los medios a esta situación. En opinión se describe el significado de los nuevos paradigmas de Internet como: interactividad, personalidad, multimedialidad, hipertextualidad, actualización, abundancia y mediación. Responde a la cuestión de ¿cómo y cuándo en la prensa latinoamericana sigue imperando la prensa amarilla? Recoge en un artículo los factores que más inciden en el éxito o fracaso de una campaña política. Aborda la implantación de una nueva moneda única en la Unión Europea y sus incidencias. Destaca las consecuencias vividas por México tras el ataque terrorista del 11 de septiembre 2001 y analiza el tratamiento que los medios dan a las informaciones procedentes del Tercer Mundo en Europa. Contesta a la pregunta inquietante sobre las posibilidades del liberalismo económico para garantizar o contrarrestar la libertad de prensa y por último se aclara los mitos y realidades que se han tejido alrededor de Windows XP de Microsoft.

  11. 'Sidun' e 'Creuza de mâ' di Fabrizio De André (1940–1999. La svolta etnica del cantautore genovese attraverso l’analisi di due canzoni esemplari

    Directory of Open Access Journals (Sweden)

    Vanna Lovato

    2014-01-01

    Full Text Available L’album Creuza de mâ (1984 di Fabrizio De André, composto e registrato grazie alla fondamentale collaborazione del musicista Mauro Pagani, rappresenta un unicum nella storia della canzone italiana, ed è più in generale un buon esempio di canzone d’autore moderna rielaborata secondo parametri musicali e linguistici diversi dagli standard della canzone di consumo tipici dell’epoca in cui l’album venne pubblicato, anticipando di quasi un decennio in Italia la moda della cosiddetta world music. Pur confermandosi ad oggi uno dei migliori esempi di ‘contaminazione’ tra canzone popolare –– rappresentata qui dall’uso del dialetto genovese –– e tradizione musicale mediterranea , nel 1984 il disco fu accolto in modo tiepido dal pubblico , ma ottenne  subito il plauso della critica e di molti colleghi ed estimatori, italiani e non; ricordiamo, tra gli altri, gli apprezzamenti fatti nel corso degli anni dal musicista inglese David Byrne.

  12. Sia la luce origini e destino del nostro universo

    CERN Document Server

    Longair, Malcolm S

    1998-01-01

    Una nuova visione dell'universo ; nascita ed evoluzione delle stelle ; quando muore una stella ; la "quasar connection" ; pulsar & co. ; gli inquietanti buchi neri ; le galassie e la nascita dell'universo.

  13. Inestabilidad compleja del codo

    Directory of Open Access Journals (Sweden)

    Héctor Gabriel Díaz Carrillo

    2014-08-01

    Full Text Available La inestabilidad compleja del codo es de reciente descripción y controversial en sus resultados; es el estado que se deriva del daño estructural y funcional, producido por la incongruencia de las superficies articulares y las estructuras ligamentosas que estabilizan el codo. Se realizó un estudio descriptivo prospectivo, en el período comprendido entre enero de 2011 y abril de 2013, en una muestra no probabilística de ocho pacientes (diez codos, seleccionados según criterios de inclusión y exclusión. Los objetivos fundamentales del estudio fueron: la actualización de conocimientos para el manejo de la enfermedad y la caracterización de los resultados obtenidos en los afectados por esta dolencia que fueron operados en el Hospital Dr. Ernesto Guevara de la Serna de la provincia de Las Tunas. Se analizaron los datos mediante técnicas estadísticas descriptivas y se realizó la evaluación clínica y radiográfica de los lesionados. El tratamiento se ejecutó según los hallazgos y consistió en: reparación ligamentosa, actuación sobre las partes óseas dañadas y colocación de osteosíntesis diversas. La edad promedio fue de 39,2 años y predominó el sexo masculino. A todos se les practicó reparación ligamentosa, siete cupulectomías y seis aplicaciones de cerclajes anti-distractores. Existieron dos reluxaciones y una sepsis local. La amplitud de movimientos fue aceptable dentro del rango compatible, con una buena función ergonómica; de acuerdo a las comparaciones bibliográficas actualizadas que se realizaron. La fijación y reparación de los estabilizadores del codo brindan buenos resultados funcionales. La sistematización en el manejo de la enfermedad, la detección de complicaciones y el arsenal terapéutico disponible son factores a tener en cuenta

  14. Nuevos usos del cemento

    Directory of Open Access Journals (Sweden)

    Páez Balaca, A.

    1977-04-01

    Full Text Available In this article, the evolution of the different systems of transporting and storing submarine oil and its by-products (petroleum gas and natural gas, is dealt with stressing the importance of the use of concrete boats. Due to the high cost of oil pipelines, we have passed from tanks built on land to prestressed concrete tanks which can be berthed at great depths or anchored to the bottom to keep them afloat, it being possible to unmoor them for transferring them. Transporting and storing liquated gas leads US to see the advantages of prestressed concrete over steel, as the latter becomes brittle at low temperatures, whereas the former's strength increases. The different forms and possible sections are analyzed, stressing the great importance of the solution of the double concrete hull with pearlite insulation. Finally, a study is made of «light concretes », not the classical types used as thermal and acoustic insulation, but the semi-heavy ones made with expanded clay, high quality sand and P-450 cement, which technique is not yet as developed in Spain at might be wished.En este artículo se trata la evolución de los distintos sistemas de transporte y almacenamiento del petróleo submarino y sus derivados (gas de petróleo y gas natural, resaltando la importancia del uso de barcos de hormigón. Debido al gran coste de los oleoductos, se ha pasado de los tanques construidos en tierra firme a los depósitos de hormigón pretensado que pueden estar fondeados a gran profundidad o anclados al fondo para mantenerlos flotantes, existiendo la posibilidad de poder desamarrarlos para su traslado. El transporte y almacenamiento del gas licuado nos hace ver las ventajas del hormigón pretensado sobre el acero, pues éste se vuelve quebradizo a bajas temperaturas, mientras aquél aumenta su resistencia. Se analizan las diferentes formas y secciones posibles, destacando la gran importancia de la solución del doble casco de hormigón con

  15. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  16. Max Weber o el enigma emocional del origen del capitalismo

    OpenAIRE

    EDUARDO BERICAT ALASTUEY

    2001-01-01

    Se analiza el trabajo clave de Max Weber, La ética protestante y el espíritu del capitalismo, desde la perspectiva de la Sociología de las Emociones. Aunque la inclusión de las emociones de los fenómenos sociales es clave para entender la idea de Weber sobre el dogma de la predestinación, los sociólogos han trivializado el papel de la emoción. Tras detallar la creencia de Weber en que el espíritu del capitalismo parte del conocimiento de que el destino del hombre está predeterminado (la ética...

  17. Sobre el significado del descubrimiento del gen FOXP2

    OpenAIRE

    Longa Martínez, Víctor Manuel

    2006-01-01

    El reciente descubrimiento del gen FOXP2 ha ofrecido la primera evidencia clara de la base genética del lenguaje, mostrando una correlación inequívoca desde la perspectiva genética entre una versión mutada de F0XP2 y los trastornos lingüísticos de diferente tipo sufridos por una familia inglesa, conocida como KE. El objetivo central del presente trabajo es discutir diferentes aspectos relacionados con tal descubrimiento; especialmente, la discusión del significado de FOXP2 con ...

  18. Competitividad sectorial internacional. Caso: sector del cuero y del calzado

    Directory of Open Access Journals (Sweden)

    Diana Carolina Villegas Álvarez

    2007-01-01

    Full Text Available El presente escrito se origina en un trabajo de investigación cuya pretensión fue indagar sobre el nivel de competitividad internacional (C.I, del sector del cuero y del calzado colombiano, mediante la aplicación de indicadores que, a partir de la información estadística de las variables de comercio exterior permiten establecer ciertas relaciones que dan cuenta de la importancia del producto en los mercados de los países de la Comunidad Andina de Naciones (CAN, seleccionados para la comparación.

  19. Bioethanol production from corn stover residues. Process design and Life Cycle Assessment; Bioetanolo da resuidui della lavorazione del mais: process design e analisi del ciclo di vita

    Energy Technology Data Exchange (ETDEWEB)

    De Bari, I; Dinnino, G; Braccio, G [Dipartimento Tecnologie per l' Energia, Fonti Rinnovabili e Risparmio Energetico, ENEA, Centro Ricerche Trisaia, Matera (Italy)

    2008-07-01

    nel centro ENEA di Trisaia: il pretrattamento a base di steam explosion e l'idrolisi enzimatica. L'impianto modellato ha una capacita di 60kt/a (dimensionato su bacini di approvvigionamento realistici in Italia); la biomassa e pretrattata con processo di steam explosion acido-catalizzato; la cellulosa e l'emicellulosa sono idrolizzate e fermentate separatamente; gli enzimi sono prodotti in situ. L'obiettivo principale e stato la minimizzazione del consumo di acqua di rete, di enzimi e di energia. I risultati indicano che la produzione di 1 kg di etanolo (95.4% in peso) richiede 3.5 kg di biomassa su base secca e produce un surplus di energia fino a 740 Wh. L'obiettivo principale dell'analisi LCA e stata la valutazione di impatto ambientale dell'intero ciclo di vita dalla produzione del bioetanolo fino al suo utilizzo in miscele E10. Il Boustead Model e stato utilizzato per compilare l'inventario di ciclo di vita. I risultati ottenuti e discussi in questo rapporto risentono di alcune limitazioni dovute principalmente ai seguenti punti: alcune rese di processo sono state estrapolate sulla base di previsioni di sviluppo ottimistiche; il recupero di energia e vapore potrebbe essere inferiore a quello calcolato per le perdite nei sistemi reali; il riciclo di acqua potrebbe essere limitato dalla tolleranza del lievito all'accumulo di potenziali sostanze tossiche. Ciononostante, la dettagliata analisi di processo sviluppata nel rapporto ha la sua importanza: nel quantificare gli obiettivi critici (ancorche ambiziosi) ai quali puntare per rendere fattibile il processo integrato; nel guidare la scelta delle tecnologie piu appropriate per superare alcuni colli di bottiglia del processo.

  20. Andrea Capra, La tecnica di misurazione del Protagora

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2011-08-01

    Full Text Available Si tratta di un articolo uscito nel 1997 presso gli ���Annali della Scuola normale superiore di Pisa. Classe di lettere e filosofia”, pp. 273-327, ora liberamente disponibile perché depositato nell’archivio istituzionale dell’Università di Milano. Gli “Annali”, infatti, almeno nel momento in cui scrivo, risultano non accessibili in rete.  Questo è un danno grave per la [...