1,721,084 research outputs found
How receptor mosaics decode transmitter signals. Possible relevance of cooperativity
No full textIt has been demonstrated that receptor–receptor interactions between G-protein-coupled receptors (GPCRs) occur at the plasma-membrane level. It has also been shown that clustering of GPCRs in aggregates or receptor mosaics (RMs) results in the reciprocal modulation of their binding and decoding characteristics. It is hypothesized that cooperativity plays an important part in the decoding of signals processed by RMs of GPCRs. Thus, the binding of the ligand at one receptor alters the likelihood of the same ligand binding at the next site, in the case of RMs, formed by identical receptors and/or by iso-receptors (receptors that bind the same ligand)
Multiple intramembrane receptor-receptor interactions in the regulation of striatal dopamine D2 receptors
No full textAdenosine A(2A), group I mGlu and neurotensin receptors have been previously found to modulate the binding characteristics of dopamine D2 receptors in membrane preparations from rat striatum. In the present study it is shown that stimulation of different combinations of striatal A(2A), group I mGlu and neurotensin receptors induce different effects on the modulation of D2 receptor binding to those obtained when they are separately stimulated using maximal effective concentrations. In competitive inhibition experiments of dopamine versus the D2 receptor antagonist [3H]raclopride the addition of the A(2A) receptor agonist CGS 21680, the group I mGlu receptor agonist DHPG or neurotensin induced a decrease in the affinity of the high affinity state of the dopamine D2 receptors for dopamine. When added together CGS 21680 plus neurotensin induced the same effect as when administered alone, CGS 21680 plus DHPG induced a synergistic effect and DHPG plus neurotensin lost their modulating effect on D2 receptor binding. These results demonstrate the existence of multiple intramembrane receptor-receptor interactions in the regulation of striatal D2 receptors
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
Receptor-receptor interactions, receptor mosaics, and basic principles of molecular network organization - Possible implications for drug development
No full textThe phenomenon of receptor-receptor interactions was hypothesized by Agnati and Fuxe in the 1980s, and
several indirect proofs were provided in the following years by means of in vitro binding experiments and in
vivo experiments in physiological and pathological animal models. This paper aims to outline some of the most
important features and consequences of this phenomenon in the frame of the structural and functional aspects
of molecular networks. In particular, the concepts of receptor mosaic (RM), and of horizontal and vertical
molecular networks (HMNs, VMNs, respectively) are illustrated. To discuss some aspects of the functional
organization of molecular networks, not only new data on protein-protein interactions but also the biochemical
mechanism of cooperativity will be used. On this basis, some theoretical deductions can be drawn that allow
a tentative classification of the RMs and the proposal of the extension of the concept of branching point introduced
for enzymes to the possible switching role of some RMs in directing signals to various VMNs. Finally, the
cooperativity phenomenon and the so-called symmetry rule will be used to introduce a proper mathematical
approach that characterizes RMs as to their receptor composition, receptor topography, and order of receptor
activation inside the RM. These new data on G protein–coupled receptors and molecular network organization
indicate possible new approaches for drug development
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
Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A(2A) dopamine D-2 and adenosine A(1) dopamine D-1 receptor interactions in the basal ganglia
No full textAn analysis at the network and membrane level has provided evidence that antagonistic interactions between adenosine A(2A)/dopamine D-2 and adenosine A(1)/dopamine D-1 receptors in the ventral and dorsal striatum are at least in part responsible for the motor stimulant effects of adenosine receptor antagonists like caffeine and for the motor depressant actions of adenosine receptor agonists. The results obtained in stably cotransfected cells also underline the hypothesis that the intramembrane A(2A)/D-2 and A(1)/D-1 receptor interactions represent functionally important mechanisms that may be the major mechanism for the demonstrated antagonistic A(2A)/D-2 and A(1)/D-1 receptor interactions found in vivo in behavioural studies and in studies on in vivo microdialysis of the striopallidal and strioentopeduncular GABAergic pathways. A major mechanism for the direct intramembrane A(2A)/D-2 and A(1)/D-1 receptor interactions may involve formation of A(2A)/D-2 and A(1)/D-1 heterodimers leading to allosteric changes that will alter the affinity as well as the G protein coupling and thus the efficacy to control the target proteins in the membranes. This is the first molecular network to cellular integration in the nerve cell membrane and may be well suited for a number of integrated tasks and can be performed in a short-time scale, in comparison with the very long-time scale observed when receptor heteroregulation involves phosphorylation or receptor resynthesis. Multiple receptor-receptor interactions within the membranes through formation of receptor clusters may lead to the storage of information within the membranes. Such molecular circuits can represent hidden layers within the membranes that substantially increase the computational potential of neuronal networks. These molecular circuits are biased and may therefore represent part of the molecular mechanism for the storage of memory traces (engrams) in the membranes. (C) 1998 Elsevier Science B.V. All rights reserved
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
Adenosine A2A agonists: A potential new type of atypical antipsychotic
No full textThe systemic intraperitoneal (i.p.) administration of the adenosine A2A agonist CGS 21680 was found to dose-dependently antagonize spontaneous and amphetamine-induced (1 mg/kg i.p.) motor activity with similar ED50 values (about 0.2 mg/kg). The ratios between the ED50 values for induction of catalepsy and for antagonizing amphetamine-induced motor activity for CGS 21680, haloperidol, and clozapine were 12,2, and > 30, respectively. Furthermore, CGS 23680 was comparably much stronger than haloperidol or clozapine at antagonizing the motor activity induced by phencyclidine (2 mg/kg subcutaneonsly) than motor activity induced by amphetamine (1 mg/kg i.p.). In conclusion, the present results show a clear "atypical" antipsychotic profile of the adenosine A2A agonist CGS 21680 in animal models. © 1997 American College of Neuropsychopharmacohgy. Published by Elsevier Science Inc
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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