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Search Results: 1 - 10 of 10786 matches for " Claudia Sissi "
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Molecular Recognition of Human Telomeric DNA by Phenanthroline-Based G-Quadruplex Ligands  [PDF]
Anna Artese, Lucia Parrotta, Stefano Alcaro, Francesco Ortuso, Giosuè Costa, Claudia Sissi
Open Journal of Medicinal Chemistry (OJMC) , 2013, DOI: 10.4236/ojmc.2013.32006
Abstract:

G-quadruplexes (G4) are non-canonical DNA structures assumed by guanine rich sequences. G4 are stabilized by the presence of cations and are characterized by a high degree of structural polymorphism with different patterns of groove, loop arrangement, strand orientations and stoichiometry. G-rich sequences are over-represented in the promoter regions of many oncogenes as well as at human telomeres, d(TTAGGG) repeats, ranging in size from 3 to 15 kb, involved in protecting chromosomal ends. A specialized enzyme, called telomerase, provides a telomere maintenance mechanism by elongating the end of the G-strand and it is activated in the majority of cancer cells. Therefore there are two general strategies of telomerase targeting in cancer treatment. One is a direct targeting of telomerase to cause its inhibition; the other one is the use of G4 stabilizers which block telomerase access to telomere, thus causing an indirect enzyme inhibition. Here, we evaluated the molecular recognition of some phenanthroline-based ligands against four different experimental models of the human telomeric sequence d[AG3(T2AG3)3] by means of docking simulations. Our theoretical analysis was able to reproduce the experimental affinity measurements, with a linear squared correlation factor r2 equal to 0.719 among all the studied models. These findings highlighted the importance to consider the polymorphism of the DNA G4. Interestingly, this correlation resulted always improved with respect to that of the single folds, with the exception of the parallel structure, thus suggesting a key role of this G4 conformation in the interaction network of the tested binders. Moreover, we identified the moieties of the phenanthroline scaffold directly involved in the complex formation. This allowed to rationalize the improved binding affinity always associated with a bis-phenanthroline system and to explain why a phenanthroline substituted with a pyridine ring is favored with respect to the pyrimidine one.

Effective DNA Inhibitors of Cathepsin G by In Vitro Selection
Barbara Gatto,Elena Vianini,Lorena Lucatello,Claudia Sissi
International Journal of Molecular Sciences , 2008,
Abstract: Cathepsin G (CatG) is a chymotrypsin-like protease released upon degranulation of neutrophils. In several inflammatory and ischaemic diseases the impaired balance between CatG and its physiological inhibitors leads to tissue destruction and platelet aggregation. Inhibitors of CatG are suitable for the treatment of inflammatory diseases and procoagulant conditions. DNA released upon the death of neutrophils at injury sites binds CatG. Moreover, short DNA fragments are more inhibitory than genomic DNA. Defibrotide, a single stranded polydeoxyribonucleotide with antithrombotic effect is also a potent CatG inhibitor. Given the above experimental evidences we employed a selection protocol to assess whether DNA inhibition of CatG may be ascribed to specific sequences present in defibrotide DNA. A Selex protocol was applied to identify the single-stranded DNA sequences exhibiting the highest affinity for CatG, the diversity of a combinatorial pool of oligodeoxyribonucleotides being a good representation of the complexity found in defibrotide. Biophysical and biochemical studies confirmed that the selected sequences bind tightly to the target enzyme and also efficiently inhibit its catalytic activity. Sequence analysis carried out to unveil a motif responsible for CatG recognition showed a recurrence of alternating TG repeats in the selected CatG binders, adopting an extended conformation that grants maximal interaction with the highly charged protein surface. This unprecedented finding is validated by our results showing high affinity and inhibition of CatG by specific DNA sequences of variable length designed to maximally reduce pairing/folding interactions.
Effect of G-Quadruplex Polymorphism on the Recognition of Telomeric DNA by a Metal Complex
Caterina Musetti, A. Paul Krapcho, Manlio Palumbo, Claudia Sissi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058529
Abstract: The physiological role(s) played by G-quadruplexes renders these ‘non-canonical’ DNA secondary structures interesting new targets for therapeutic intervention. In particular, the search for ligands for selective recognition and stabilization of G-quadruplex arrangements has led to a number of novel targeted agents. An interesting approach is represented by the use of metal-complexes, their binding to DNA being modulated by ligand and metal ion nature, and by complex stoichiometry. In this work we characterized thermodynamically and stereochemically the interactions of a Ni(II) bis-phenanthroline derivative with telomeric G-quadruplex sequences using calorimetric, chiroptical and NMR techniques. We employed three strictly related sequences based on the human telomeric repeat, namely Tel22, Tel26 and wtTel26, which assume distinct conformations in potassium containing solutions. We were able to monitor specific enthalpy/entropy changes according to the structural features of the target telomeric sequence and to dissect the binding process into distinct events. Interestingly, temperature effects turned out to be prominent both in terms of binding stoichiometry and ΔH/ΔS contributions, while the final G-quadruplex-metal complex architecture tended to merge for the examined sequences. These results underline the critical choice of experimental conditions and DNA sequence for practical use of thermodynamic data in the rational development of effective G-quadruplex binders.
Effective DNA Inhibitors of Cathepsin G by In Vitro Selection
Barbara Gatto,Elena Vianini,Lorena Lucatello,Claudia Sissi,Danilo Moltrasio,Rodolfo Pescador,Roberto Porta,Manlio Palumbo
International Journal of Molecular Sciences , 2008, DOI: 10.3390/ijms9061008
Abstract: Cathepsin G (CatG) is a chymotrypsin-like protease released upon degranulation of neutrophils. In several inflammatory and ischaemic diseases the impaired balance between CatG and its physiological inhibitors leads to tissue destruction and platelet aggregation. Inhibitors of CatG are suitable for the treatment of inflammatory diseases and procoagulant conditions. DNA released upon the death of neutrophils at injury sites binds CatG. Moreover, short DNA fragments are more inhibitory than genomic DNA. Defibrotide, a single stranded polydeoxyribonucleotide with antithrombotic effect is also a potent CatG inhibitor. Given the above experimental evidences we employed a selection protocol to assess whether DNA inhibition of CatG may be ascribed to specific sequences present in defibrotide DNA. A Selex protocol was applied to identify the single-stranded DNA sequences exhibiting the highest affinity for CatG, the diversity of a combinatorial pool of oligodeoxyribonucleotides being a good representation of the complexity found in defibrotide. Biophysical and biochemical studies confirmed that the selected sequences bind tightly to the target enzyme and also efficiently inhibit its catalytic activity. Sequence analysis carried out to unveil a motif responsible for CatG recognition showed a recurrence of alternating TG repeats in the selected CatG binders, adopting an extended conformation that grants maximal interaction with the highly charged protein surface. This unprecedented finding is validated by our results showing high affinity and inhibition of CatG by specific DNA sequences of variable length designed to maximally reduce pairing/folding interactions.
Sublima??o e clínica psicanalítica
Castiel, Sissi Vigil;
Psicologia: Ciência e Profiss?o , 2010, DOI: 10.1590/S1414-98932010000100003
Abstract: since its primeval times, the analytical technique has been the possibility for both, the word and the symbolic, to emerge. however, this process goes through many disruptions, as the strategies of the clinic are remodeled. i intend to outpoint these transformations as well as the impasses which freud’s analytical technique goes under, until its final form. in this context i intend to highlight the role of sublimation in the clinic and its relation with the direction of the cure, in the sense that the creations of a subject are important part of the analytical process therapeutic dimension.
Sentido arendtiano de la “banalidad del mal”
Sissi Cano Cabildo
Horizonte : Revista de Estudos de Teologia e Ciências da Religi?o , 2009, DOI: 10.5752/567
Abstract: En su obra Eichmann en Jerusalén Arendt habla de la “banalidad del mal” para referirse a la ambigüedad del concepto de maldad por el que algunas personas pueden ser manipuladas por conceptos frívolos de lo bueno y de lo malo, banalidad que no minimiza la crueldad de sus efectos. Este enfoque arendtiano no pretende explicar, ni definir de forma total a la maldad, más bien deviene en una crítica a la trivialidad de los conceptos cerrados y dogmáticos de la maldad por los que se puede atentar contra la vida o la dignidad de las personas. La autora refiere esta tesis a partir del seguimiento del caso Eichmann, quien siempre se mostró orgulloso de su colaboración con el genocidio nazi. Arendt explica la “banalidad del mal” a partir de la falta de pensamiento; sólo el pensamiento como autorreflexión que busca el significado puede prevenirnos de criterios que pueden ser altamente perniciosos. Ahora bien, la actualización del pensamiento no depende del nivel informativo ni del contexto histórico, sino que sólo depende de la libertad del Sujeto, por lo que no hay prescripciones universales para atreverse a pensar. Palabras clave: Banalidad del mal; Pensamiento; Autorreflexión; Significado y libertad. ABSTRACT Arendt talk abaut “banality of badness” in Eichmann in Jerusalem to refer the ambiguous criteria of badness which lead to manipulation’s people; so much people can follow frivolous concept of goodness and badness, and it banality don’t diminish the cruelty abaut consequences. It arendtian’s sence don’t try to explain the universal sence of the badness, it’s only a criticism abaut the triviality of the dogmatics concepts of badness wich can to attempt the life and the dignidty of so much persons. Arendt refer it sence of “banality of badness” because of the pursuit Eichmann’s prosecute; Eichmann always seems proud by his colaboration with the nazism. Arendt explain the banality of badness because the absence of thought, only the thought as a self-reflection process might prevent us from having ambiguous criteria which could be very pernicious. Now, to think don’t depend the informativ level neither the historic context, to think only depend abaut the fry, consequently there aren’t universal prescriptions for to dare do thinking. Key words: Banality of badness; Thought; Self-reflection process; Meaning and fry.
Psicodramatizando a constru o da cidadania
Sissi Malta Neves
Psicologia: Ciência e Profiss?o , 1996, DOI: 10.1590/s1414-98931996000100005
Abstract:
Implica es metapsicológicas e clínicas da conceitua o da sublima o na obra de Freud
Castiel, Sissi Vigil
Psico , 2006,
Abstract: Este trabalho tem como objetivo pensar nas diversas formula es freudianas a respeito da sublima o, a medida em que se trata de um conceito que n o foi plenamente elaborado. Para tanto, se faz uma articula o com as diversas rupturas empreendidas por Freud no conceito de sexualidade. Além disso, trata-se de articular o conceito de sublima o com outros conceitos metapsicológicos e clínicos de maneira que se possa ampliá-lo.
Desenvolvimento de tomate de mesa, com o uso do método QFD (Desdobramento da Fun??o Qualidade), comercializado em um supermercado
Marcos, Sissi K.;Jorge, José Tadeu;
Horticultura Brasileira , 2002, DOI: 10.1590/S0102-05362002000300019
Abstract: to attend the consumer's requirements related to the fresh tomato, offering a product of quality and to reduce the post-harvest losses of the product, the qfd method was applied to the tomato commercialized in a supermarket. the potential use of this tool was appraised, as well as its applicability to an agricultural product, taking effect the qfd. the experiment was carried out at the carrefour store in campinas, brazil. a product with the requirements demanded by the consumer was developed, having the 'carmen' tomato (popularly known by long shelf life) as the rival, which retains the biggest share in market nowadays. at each step of the experiment, the decisions were taken, considering the inherent characteristics to the product and its relations with the methodology. the pilot lot, with characteristics demanded by the clients and suitable to the business strategy (supermarket), was evaluated with the consumers. the established goal in relation to quality was reached, as well as the aim related to losses. losses were %. as to the preference test, in which the developed product and 'carmen' tomato were compared, through sensorial analysis, the tomato developed by the qfd method was the favorite with 0,1% significance level. the results obtained proved the applicability of the qfd method to fresh agricultural products commercialized, and the expected benefits were reached.
Desenvolvimento de tomate de mesa, com o uso do método QFD (Desdobramento da Fun o Qualidade), comercializado em um supermercado
Marcos Sissi K.,Jorge José Tadeu
Horticultura Brasileira , 2002,
Abstract: Para atender as exigências do consumidor, relativas ao tomate de mesa, oferecendo um produto de qualidade, e reduzir as perdas pós-colheita, aplicou-se o método QFD ao tomate comercializado em um supermercado. Avaliou-se o potencial de uso dessa ferramenta, bem como sua aplicabilidade a um produto hortícola, tendo-se realizado o desdobramento da qualidade, com o trabalho conduzido na loja Carrefour D.Pedro, em Campinas. Desenvolveu-se um produto a partir das características exigidas pelo consumidor, estabelecendo-se como concorrente o tomate 'Carmem'. A cada etapa do método, as decis es foram tomadas após discuss es norteadas pelas características inerentes ao produto e suas rela es com a metodologia. O lote piloto, com as características exigidas pelos clientes e condizentes com as estratégias da empresa (supermercado), foi avaliado junto aos consumidores e atingiu as metas estabelecidas para a qualidade planejada, bem como o objetivo relativo a perdas, tendo-se alcan ado o valor de 0% de perdas. No teste de preferência, em que se comparou o produto desenvolvido com o tomate 'Carmem', através de análise sensorial, o tomate desenvolvido através do método QFD foi o preferido ao nível de 0,1% de significancia. Os resultados obtidos comprovaram a aplicabilidade do método QFD a produtos agrícolas comercializados in natura, tendo-se alcan ado os benefícios esperados.
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