1,721,138 research outputs found
Recent updates in CFTR structural studies: opportunities and challenges for cystic fibrosis drug development
No full textAn Update on CFTR Drug Discovery: Opportunities and Challenges
No full text: The Biomolecules Special issue on "An Update on CFTR Drug Discovery: Opportunities and Challenges" includes three original research articles and a webinar session focusing on some recent findings concerning CFTR drug discovery [...]
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
Exploring the selectivity profile of sigma receptor ligands by molecular docking and pharmacophore analyses.
No full textsRs),
Background: Sigma receptors (
initially classified as an additional class of opioid receptors, are
now recognized as a unique entity with no homology to opioid receptors divided into two distinct
s1R
s2R.
subtypes namely
and
.1R-targeting ligands have been conceived and explored for the
s2R
treatment of various neurodegenerative disorders and neuropathic pain. Activation of the
appears
to be involved in the regulation of cellular proliferation and cell death.
s1R
Objective: Up to now, the rational design of novel
ligands was efficiently guided by
computational methods, especially relying on homology modeling studies. Conversely, the limited
s2R-
number of in silico studies was applied in the search of
targeting compounds. Herein we explored
by computational methods several series of .1R ligands featuring variable selectivity profile towards
s1R
s
and
R in order to gain useful information guiding the rational design of more selective ligands.
.
s1R,
Methods: Based on the recent X-ray crystallographic structure of the human
deepening
sR
molecular docking studies on different series of
ligands have been performed. These calculations
have been followed by molecular dynamic simulations (MD) and by two pharmacophore analyses,
s1R
s
taking into account the activity levels towards
and
.R.
Results: Structure-based studies revealed key contacts to be achieved in order to guide selectivity of
s1R
-targeting compounds while the two pharmacophore models described the main features turning in
s1R
s2R
effective
or
ligands.
Conclusion: The applied computational approach allowed a more comprehensive exploration of the
structure-activity relationship (SAR) within the herein analyzed .R ligands, deriving useful guidelines
for the rational design of more selective compounds
Insights into the Structure and Pharmacology of the Human Trace Amine-Associated Receptor 1 (hTAAR1): Homology Modelling and Docking Studies
No full textTrace amine-associated receptor 1 (TAAR1) is a G proteincoupled receptor that belongs to the family of TAAR receptors and responds to a class of compounds called trace amines, such as -phenylethylamine (-PEA) and 3-iodothyronamine (T1AM). The receptor is known to have a very rich pharmacology and could be also activated by other classes of compounds, including adrenergic and serotonergic ligands. It is expected that targeting TAAR1 could provide a novel pharmacological approach to correct monoaminergic dysfunctions found in several brain disorders, such as schizophrenia, depression, attention deficit hyperactivity disorder and Parkinson's disease. Only recently, the first selective TAAR1 agonist RO5166017 has been identified. To explore the molecular mechanisms of proteinagonist interaction and speed up the identification of new chemical entities acting on this biomolecular target, we derived a homology model for the hTAAR1. The putative protein-binding site has been explored by comparing the hTAAR1 model with the 2-adrenoreceptor binding site, available by X-ray crystallization studies, and with the homology modelled 5HT1A receptor. The obtained results, in tandem with docking studies performed with RO5166017, -PEA and T1AM, provided an opportunity to reasonably identify the hTAAR1 key residues involved in ligand recognition and thus define important starting points to design new agonists
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
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