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A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25
No full textHepcidin is a new peptide hormone secreted by the liver and widely distributed among animals, from fish to human. It acts as a signal molecule in iron metabolism and plays an important role in iron overload diseases. Recently, it has been reported that hepcidin is able to regulate the iron efflux by binding to the ferroportin protein and inducing its internalization. This activity is specific only for bioactive hepcidin-25 and not for the truncated hepcidin-20, lacking the five amino terminal residues. We have characterized the N-terminal region of the hepcidin-25 as a metal-binding site by several spectroscopic techniques and chemical studies. This region, specific for the coordination of Cu(II) and Ni(II), is known as 'ATCUN motif'. Moreover, we have demonstrated that the metal binding inhibits the aggregation propensity of both whole hepcidin-25 and its N-terminal fragments, probably inducing a conformational change leading to the stabilization of the N-terminal region. The identification of a metal-binding site at the N-terminus of hepcidin-25, which is necessary for its biological activity as iron-regulatory hormone, will help us to cast light both on the role of the divalent metals and of the hepcidin-25 in the iron homeostatis, and to better understand structure-function relationships of this hormone-peptide
Structural and dynamical properties of KTS-disintegrins: a comparison between Obtustatin and Lebestatin
No full textObtustatin and Lebestatin are lysine-threonine-serine (KTS)-disintegrins, which are a family of low molecular weight polypeptides present in many viperidae venoms and are potent and specific inhibitors of collagen-binding integrins. The integrin binding loop, harboring the 21KTS23 motif, and the C-terminal tail are known to be responsible for the selective binding to the α1β1 integrin. Despite a very high sequence homology (only two mutations are present in Lebestatin relative to Obtustatin, namely R24L and S38L), Lebestatin exhibits a higher inhibitory effect than Obtustatin on cell adhesion and cell migration to collagens I and IV. Here we show, by means of molecular dynamics simulations of the two polypeptides in aqueous solution, that Lebestatin possesses a higher flexibility of the C-terminal tail and a greater solvent accessibility of the integrin binding loop than Obtustatin. It may be hypothesized that these properties may contribute to the higher binding-affinity of Lebestatin to its biological partne
Progressi nella sintesi totale regio e stereoselettiva del diterpene tetraciclico (+) stemarin
No full textAtti pag. 42
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Pro-oxidant activity of histatin 5 related Cu(II)-model peptide probed by mass spectrometry
No full textHistatin 5 is a cationic salivary peptide with strong candidacidal and bactericidal activity at physiological concentration. In this paper we demonstrate by optical spectroscopy and ESI-IT-MS experiments that a synthetic peptide related to the N-terminus of histatin 5 specifically binds copper ions in vitro and that the complex metal-peptide generates reactive oxygen species at physiological concentration of ascorbate, leading to significant auto-oxidation of the peptide within short reaction time. The oxidative activity of this peptide is associated to the presence of a specific metal binding site present at its N-terminus. The motif is constituted by the amino acid sequence NH2-Asp-Ser-His, representing a copper and nickel amino terminal binding site, known as "ATCUN motif". The results of the study suggest that the production of reactive oxygen species can be an intrinsic property of histatin 5 connected to its ability to bind metals
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