1,721,079 research outputs found
Influence of allosteric Hsp90 ATPase activators on its chaperoning activity
No full textHsp90 is a molecular chaperone with a starring role in the cell life cycle1 and an established anti-apoptotic target in cancer therapy.2 The protein internal dynamics are regulated by ATP and are critical for its function. Hsp90 can be modulated in an allosteric fashion as we have recently demonstrated, targeting the protein C-terminal domain (CTD) with a family of 2-phenyl-benzofuran derivatives.3-5 These compounds accelerate Hsp90 internal dynamics and increase its enzymatic ATPase activity. As a result, they tune its chaperone activity in ways that we are just beginning to unravel.
The synthetic approaches towards an expanded library of about 40 benzofuran derivatives will be presented. The interaction studies with full length Hsp90,6 and the effects on Hsp90 enzymatic and chaperoning activity will be reported for selected compounds.
References
1. S. E. Jackson In Molecular Chaperones; Jackson, S., Ed.; Springer Berlin Heidelberg (2013) Vol. 328, p 155-240.
2. J. Trepel, M. Mollapour, G. Giaccone, and L. Neckers Nat Rev Cancer (2010), 10, 537-549.
3. L. Morelli, A. Bernardi and S. Sattin, Carbohydr. Res. (2014), 390, 33-41.
4. S. Sattin et al Chem. Eur. J. (2015), 21, 13598-13608.
5. G. Vettoretti, E. Moroni, S. Sattin, J. Tao, D.A. Agard, A. Bernardi and G. Colombo Sci Rep (2016), 6, 23830.
6. S. Sattin, M. Panza, F. Vasile, F. Berni, G. Goti, J. Tao, E. Moroni, D.A. Agard, G. Colombo and A. Bernardi
Eur. J.Org. Chem. (2016) DOI: 10.1002/ejoc.201600420
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Investigating the interaction of peptidomimetic ligands with e-cadherin using NMR and computational studies
Full text linkClassical cadherins are versatile calcium-dependent cell–cell adhesion proteins, differentially and specifically expressed in different tissues. Cadherins form homophilic cell–cell interactions by forming dimers between the N-terminal extracellular domains of two cadherins on adjacent cells. Cadherins are known to play a key role in important physiological processes, such as tissue morphogenesis and stability, as well as in the immune system regulation [1]. Over the past 20 years,the expression and/or the dysregulation of several cadherins have been shown to correlate with tumor progression [2]. Thus, cadherins are becoming valuable diagnostic indicators as well as potential therapeutic targets.Recently, our group set up a docking protocol to rationally design small peptidomimetic ligands mimicking the N- and E-cadherin adhesive homodimer interface. Accordingly, the first mimics based on the tetrapeptide sequence Asp1-Trp2-Val3-Ile4 (DWVI) of the N-terminal EC1 domain were achieved (by replacing the central dipeptide Trp2-Val3 with several scaffolds developed in our laboratories) and proved to inhibit adhesion of epithelial ovarian cancer cells with millimolar potency [3]. Molecular Dynamics (MD) simulations were performed starting form the most representative docking poses to discriminate between the stable and unstable docked poses and to equilibrate the system to achieve a stable conformation. MD trajectories have been analyzed according to the experimental information on ligand-cadherin interaction obtained by STD (Saturation Transfer Difference) NMR experiments in the presence of EC1-EC2 construct of the epithelial E-cadherin. NMR data and MD simulations suggest a highly dynamic behavior of both the ligand and the protein and prompt towards an integrated computational and experimental approach to design new small peptidomimetic molecules able to interfere efficiently with cadherin-mediated cell-cell adhesion.
Acknowledgements: we gratefully acknowledge Ministero dell’Università e della Ricerca for financial support (FIRB project RBFR088ITV).
References
1) D. Leckband, S. Sivasankar, Curr. Opin. Cell Biol. 2012, 24, 620.
2) G. Berx, F. van Roy, Cold Spring Harbor Perspectives in Biology 2009, 1, a003129.
3) F. Doro, C. Colombo, C. Alberti, D. Arosio, L. Belvisi, C. Casagrande, R. Fanelli, L. Manzoni, E. Parisini, U. Piarulli, E. Luison, M. Figini, A. Tomassetti, M. Civera, Org. Biomol. Chem. 2015, 13, 2570
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