1,720,964 research outputs found
Novel fluorescent hA3 adenosine receptor antagonists.
No full textActivation of the Gi protein-coupled A3 adenosine receptor (AR) is associated with anticancer, antiischemic and anti-inflammatory effects. hA3 AR antagonists are being examined as promising agents for the treatment of glaucoma.1
Fluorescent probes are useful tools to investigate specific subcellular components in cells, tissues and organisms. In high throughput screening, fluorescent ligands represents a safer, more powerful and more versatile alternative to radioligands.2
We have recently reported a series of pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) based fluorophore-conjugated hA3 AR antagonists.3 Unfortunately, none of them reached affinities in the nM range. Here we report a novel series of PTP based fluorophore-conjugated hA3 AR antagonist with an additional pharmacophoric group at the 5-position, in order to obtain more potent hA3 AR antagonists.
References
1. Müller, C.E.; Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta 2011, 1808, 1290-1308.
2. Kuder,K.; Kiec-Kononowicz, K. Fluorescent GPCR ligands as new tools in pharmacology. Curr. Med. Chem. 2008, 15, 2132–2143.
3. Kozma, E.; Kumar, T.S.; Federico, S.; Phan, K.; Balasubramanian, R.; Gao, Z.G.; Paoletta, S.; Moro, S.; Spalluto, G.; Jacobson, K.A. Novel fluorescent antagonist as a molecular probe in A3 adenosine receptor binding assays using flow cytometry. Biochem. Pharmacol. 2012, 83, 1552-1561
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
Fluorescent ligands for the A3 adenosine receptor.
No full textFluorescent probes are useful tools to investigate specific subcellular components in cells, tissues and organisms. A classic application of fluorescent ligands of a specific GPCR (G-protein coupled receptors) is the investigation of the receptor location, and, if their binding is reversible, it could provide pharmacological information such as affinity and proximity between interacting molecules. In cultured cell systems, methods based on fluorescence have permitted to observe the receptor cycling and the formation of oligomeric receptor complexes. In high throughput screening, fluorescent ligands represents a safer, more powerful and more versatile alternative to radioligands. [1]
The introduction of the bulky fluorophore into a small molecule ligand could lead to deep modifications not only from a physicochemical point of view but also in its pharmacological properties. [2] In order to allow a correct interaction of the pharmacophore with its receptor, it is usually separated from the fluorophore by a linker or a spacer, which should be attached at a specific position that doesn't interfere with the ligand activity. Length and chemical nature of this spacer are optimised in order to obtain the desired biological activity. Also, the choice of the fluorescent molecule to link to the ligand is very important. [1,3]
We decided to develop a fluorescent-ligand for the A3AR (A3 adenosine receptor) subtype using the pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) as active scaffold at the hA3AR. [4] PTP bears a alkyldiamino spacer at the 5 position which possess a terminal amino group that could be functionalized with the fluorescein isothiocyanate (FITC). FITC represent a useful fluorescent tool because shows a significant extinction coefficent, high quantum yields, and water solubility. [3]
The homology model of the hA3AR based on the crystal structure of the hA2AAR was used to perform the docking studies of conjugated derivatives (Prof. Stefano Moro, University of Padua) in order to evaluate what interactions occurs inside the binding pocket.
References
[1] R.J. Middleton, B. Kellam. Fluorophore-tagged GPCR ligands. Curr. Opin. Chem. Biol. 2005, 9, 517-525.
[2] R.P. Haughland. Introduction to fluorescence techniques. Handbook of Fluorescent Probes and Research Products. Chapter 1. 2002 Eugene, Oregon: Molecular Probes.
[3] N. Baindur, D.J. Triggle. Concepts and progress in the development and utilization of receptor-specific fluorescent ligands. Med. Res. Rev. 1994, 14, 591-664.
[4] S.L. Cheong, S. Federico, G. Venkatesan, et al. The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry and in silico approaches. Med. Res. Rev. In press: DOI 10.1002/med.2025
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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