1,721,182 research outputs found
Correlation energy contribution to nuclear masses
No full textDuring the last few years, much effort has been made to develop a microscopic description of the nuclear masses based on mean field theory. The accuracy achieved, when phenomenological parameters are added to take specific effects into account (Wigner term, cut-off in pairing space, etc.), leads to a rms of 0.6–0.7 MeV [S. Goriely, F. Tondeur, J.M. Pearson, Atom Data Nucl. Data Tables 77 (2001) 311] (see also [M. Bender, P.H. Heenen, P.G. Reinhard, Rev. Modern Phys. 75 (2003) 121]). We present evidence that further progress can be made by taking into account medium polarization effects associated with surface and pairing vibrations [S. Baroni, M. Armati, F. Barranco, R.A. Broglia, G. Colò, G. Gori, E. Vigezzi, J. Phys. G: Nucl. Part. Phys. 30 (2004) 1353; S. Baroni, F. Barranco, P.F. Bortignon, R.A. Broglia, G. Colò, E. Vigezzi, Phys. Rev. C 74 (2006) 024305] (see also [M. Bender, G.F. Bertsch, P.-H. Heenen, Phys. Rev. C 73 (2006) 034322])
"Tractatus de coloribus": Classification of Colours in a 16th Century Unpublished Treatise in the Collection of Gian Vincenzo Pinelli at the Biblioteca Ambrosiana
No full textTissue and subcellular localization of mammalian renalase, a FAD-containing protein involved in the pathogenesis of cardiovascular diseases
No full textRenalase is a secretory protein and flavoenzyme that is ubiquitous in vertebrates and conserved in some other phyla. In mammals it has been shown to modulate cardiovascular responses, being particularly active in decreasing catecholaminergic tone, lowering blood pressure, and in protecting the heart against ischemic damage (1). Lowered renalase levels in tissue and plasma might be the basis of the cardiovascular complications observed in chronic kidney disease patients (1). Renalase secretion into the circulation is enhanced in response to stressors such as hypotension, but the molecular mechanism regulating its basal or stimulated secretion are unknown(2). We find that renalase has a signal-sequence, but this sequence is not cleaved prior to its secretion, suggesting that it may traffic in an atypical secretory pathway. In pig kidney, our immunofluorescence studies showed that renalase is exclusively expressed in the proximal tubule. Similar studies in human immortalized HK-2 cells, as well as on pig and mouse primary cell lines, indicated that renalase is preferentially localized in the cytoplasm, where it shows a punctate distribution, suggestive of an organelle association. The identification of these subcellular compartment(s), mechanism of association, and renalase’s mechanism of secretion are underway. This knowledge could lead to novel therapies for cardiovascular and kidney diseases (3).
This work has been supported by travel fellowships granted by the Italian Society of Biochemistry and Molecular Biology (SIB) and by the Consorzio Interuniversitario di Biotecnologie to S. Baroni.
1. Desir GV. Curr Opin Nephrol Hypertens. 2011; 20: 31-6.
2. Milani M, et al. J Mol Biol. 2011; 411: 463-73.
3. Unger T, et al. Eur Heart J. 2011; 32: 2739-47
NEW INSIGHTS INTO THE STRUCTURAL AND BIOCHEMICAL PROPERTIES OF HUMAN RENALASE: A NOVEL FLAVOENZYME INVOLVED IN BLOOD PRESSURE REGULATION
Full text linkAbstract
Renalase is a flavoprotein recently discovered in humans, which is ubiquitous in vertebrates and conserved in some other phyla. In 2005, it was identified within a project aimed to determine novel proteins secreted by the kidney, whose defect could explain the high incidence of cardiovascular complications in patients with chronic kidney disease (Xu et al., 2005). The protein is preferentially expressed in the renal proximal tubules and heart, and it’s secreted in blood and urine.
Genetic, epidemiological, clinical studies and animal experimental models have constantly accumulated evidence of the important role played by renalase in lowering blood pressure, decreasing the catecholaminergic tone and control heart function. A renalase knockout mouse model resulted in increased levels of catecholamines in plasma and heart, cardiac ischemia and myocardial necrosis more severe than WT littermates (Wu et al., 2011). However, the possible molecular mechanism, the nature of the in vivo catalyzed reaction and the identity of renalase substrate(s) are still unclear.
Based on these premises, the main aim of the project was to provide a detailed biochemical and structural characterization of renalase in order to better elucidate its physiological function.
We solved the crystallographic structure of recombinant human renalase at 2.5 Å resolution. The general fold classified it as a member of the p-hydroxybenzoate hydroxylase family. Renalase contains non-covalently bound FAD with redox features suggestive of a oxidase or NAD(P)H-dependent monooxygenase activity (Milani et al., 2011), in contrast with the proposed activity of catecholamine degradation via a superoxide (O2-)-dependent mechanism (Farzaneh-Far et al., 2010). Furthermore, structural evidence indicates that the proposed secretion signal of renalase could not be cleaved without disrupting the protein native conformation, suggesting that renalase trafficking occurs through an atypical secretory pathway.
The resolution of renalase crystallographic structure and the biochemical data available will hopefully provide the basis towards the understanding of the molecular mechanism of renalase physiological action, which is expected to favor the development of novel therapeutic tools for the treatment of kidney and cardiovascular diseases.
During the PhD program, I was also involved in a side project focused on the elucidation of the role of Y258 residue of P. falciparum Ferredoxin-NADP+ reductase (PfFNR) in the control of NADPH specificity.
PfFNR is a FAD-containing enzyme able to promote the transfer of two electrons from NADPH to ferredoxin and represents a promising target of novel antimalarial drugs.
Rapid reactions kinetics, active site titrations with NADP+ and anaerobic photoreduction experiments allowed us to conclude that the Y258 side chain favors the stabilization of the catalytically competent conformation of the MNM moiety of NADPH, enhancing the hydride transfer between the nicotinamide nucleotide and the FAD prosthetic group.
The almost complete abolishment of NADPH selectivity has never been accomplished before through a single mutation
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
Creation and Colouration of Stained-Glass Windows in Mediaeval Literary Sources : New Perspectives on Technical Treatises Dated Between the 12th adn 16th Centuries
No full text
Processi molecolari coinvolti nell'attività anti-biofilm: approccio proteomico multi-strategico
No full textLo sviluppo e la funzionalità di un nuovo materiale antibiofilm non può prescindere dalla comprensione dei meccanismi molecolari che permettono alle molecole che lo compongono di impedire la formazione di un biofilm microbico. Il problema è stato affrontato applicando diversi approcci proteomici. In uno di questi, si è partiti dal presupposto che tali molecole esercitino un'interferenza con la formazione del biofilm mediante l'alterazione di specifici processi molecolari e cellulari del microorganismo sotto bersaglio. Un altro approccio invece nasce dalla condiderazione che un dato composto antibiofilm funzioni interagendo con un bersaglio costituito da una o più proteine specifiche del microorganismo che sono coinvolte in una delle fasi della formazione del biofilm o nel suo mantenimento
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
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