1,721,016 research outputs found
Biostructural studies on PPAR nuclear receptors
Full text linkThe peroxisome proliferator-activated receptors (PPARs) represent a family of nuclear receptors that function as ligand-activated transcription factors, regulating genes involved in cell differentiation and various metabolic processes, especially lipid and glucose homeostasis. The PPAR family comprises three isoforms: PPARα, PPARβ/δ and PPARγ, with different tissue distribution, ligand specificitiy and physiological role. Because of their wide range of actions on glucose homeostasis, lipid metabolism and vascular inflammation, PPARs represent promising targets for the development of new drugs for the treatment of metabolic disorders such as type 2 diabetes mellitus (T2DM), dyslipidemia and atherosclerosis. Among all the subtypes, despite the undesiderable side effects associated to the drug treatment, PPARγ is still the most widely studied for its crucial role in the complex cross-talk between metabolically active tissues essential for energy balance. Then, new combination strategies using dual or pan agonists, as well as selective modulators, are currently in development.
This study is aimed to understand in deep the dynamic personality of the nuclear receptors PPAR in complex with both natural and synthetic ligands that, interacting with different regions of the LBD, confer a differentiated biological response in cellular and animal models. PPARs could be then described as a ‘functionally pluripotent’ proteins being their activity mediated by ligands that, causing the functional site to adopt an active/inactive conformations, activate different structural and biological pathways depending on the co-activator/co-repressor recruited.
Through a structural approach we propose to get more insights on how the biological response is variably affected by ligands depending on their binding mode and even the mutation of a single residue responsible for a structural destabilization of the LBD could be associated to rare genetic disorder.
The understanding of such a mechanism required the use of more than one biophysical technology. X-ray diffraction was used as the main approach to investigate the binding mode of the selected ligands. In addition, the binding has been also characterized using other biophysical techniques such as Isotermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR) to obtain thermodynamic and kinetic parameters of the binding
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
Structure of the 4:1 inclusion compound between deoxycholic acid and (E)-p-dimethylaminoazobenzene.
Full text linkImmobilized peroxisome proliferator-activated receptors (PPARs) as target for biochromatographic studies useful in medicinal chemistry investigations
No full textDispelling 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
Stereoselectivity by Enantiomeric Inhibitors of Matrix Metalloproteinase-8: New Insights from Molecular Dynamics Simulations
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