1,720,972 research outputs found
Computer-aided design of peptidomimetic molecules targeting cadherin-mediated protein-protein interactions
No full textCadherins are cell-cell adhesion proteins which are overexpressed in several solid tumors. They contain an extracellular region consisting of five immunoglobulin-like domains (EC1–EC5) that extend from the cell surface. In 1995, structural data of the N-cadherin suggested an homodimeric interface involving the peptide chains HAVDI and INPI contained in the middle EC1 sequence. Based on these studies, mimics of His-Ala-Val sequence have been patented. More recently, the crystal structures of the complete (EC1-EC5) ectodomains of N- and E-cadherins have been solved highlighting that cadherins dimerize through a ‘strand-swap’ trans-adhesive interface involving the N-terminal EC1 domains.
In this framework, a thorough study of the adhesion dimer structures was attempted with the aim of characterizing cadherin binding interfaces and developing computational tools for the design of small peptidomimetics that target the homophilic interactions of the extracellular cadherin domains. Possible approaches included mapping the hotspot interactions into pharmacophores for database screening and mapping the epitope of one of the proteins onto a small peptidomimetic.
The communication will discuss the first results obtained in the computer-aided design, focusing on the most promising peptidomimetics found by virtual screening of database and rational design of small libraries of tetrapeptide mimics (Figure 1). The synthesis of few candidates has already been completed and their biological evaluation started
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
Reconstructing the free energy landscape of E-Cadherin conformational transition by metadynamics simulations
No full textIn classical cadherins, the mechanism by which three dimensional (3D) domain swapping leads to protein dimerization is still debated[1]. According to the 3D swapping model, two cadherin monomers mutually exchange a small portion of their N-terminal extracellular domain and form a homodimer. Two possible dimerization pathways have been proposed: a selected fit mechanism, based on the hypothesis that only monomers in an active conformational state can bind, and the induced fit mechanism, which requires the formation of an intermediate complex preceding the dimerization. Exploiting the advantages of metadynamics simulations in sampling protein conformational changes, the selected fit mechanism has been tested by reconstructing the free energy profile of E-cadherin monomer conformational change, leading to the active form. Calculations have also showed that the E-cadherin free state conformational equilibrium is strongly affected by the presence of calcium ions, which behave as allosteric activators in the opening process.
We acknowledge HPC-Europa2 Programme (Application number 1024) and the Ministero dell'Università e della Ricerca (bando FIRB 2008 RBFR088ITV) for financial support
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
Synthesis and conformation evaluation of α-N-linked glycopeptides
No full textThe synthesis of neo-glycoconjugates has been gaining much attention in recent years, due to the relevance of natural glycopeptides and glycoproteins in human health and disease. Our group has been actively investigating the synthesis of α-N-linked glycosyl amides and glycopeptides. These compounds are practically unknown in nature and may lead to molecules tolerated by biological systems and yet less susceptible to chemical or enzyme-mediated hydrolysis. The synthesis of these unnatural compounds is not trivial because only few methods are available for α-N glycosylation. Recently, a route to obtain α-N-linked glucosyl asparagine was introduced by DeShong and co-workers.3 Starting from this strategy we were able to optimize and scale up the stereoselective synthesis of α-N-glycosylated building blocks of glucosyl and galactosyl asparagine with suitable protecting groups for solid phase peptide synthesis. The resulting α-N-linked glycosylaminoacids were initially employed in solution to determine activation conditions for both C-terminus and N-terminus elongation. After identification of appropriate condensing agents and deprotection conditions, solid phase synthesis (Fmoc protocol) was explored for the synthesis of more complex α-N-linked glycopeptides. The preparation of short model α-N-linked glycopeptides has allowed to initiate the study of conformation and properties of these neo-glycoconjugates
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
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