1,721,027 research outputs found
Diadenosine homodinucleotide products of ADP-ribosyl cyclase behave as modulators of the purinergic receptor P2X7
No full textADP-ribosyl cyclases from both vertebrates and invertebrates were previously shown to produce two isomers of P1,P2 diadenosine 5',5'"-P1, P2-diphosphate, P18 and P24, from cyclic ADP-ribose (cADPR) and adenine. P18 and P24 are characterized by an unusual N-glycosidic linkage in one of the adenylic mononucleotides (Basile, G., Taglialatela-Scafati, O., Damonte, G., Armirotti, A., Bruzzone, S., Guida, L., Franco, L., Usai, C., Fattorusso, E., De Flora, A., and Zocchi, E. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 14509-14514). P24, but not P18, proved to increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) in HeLa cells and to negatively affect mitochondrial function. Here we show that micromolar P24, but not P18, triggers a slow and sustained influx of extracellular Ca(2+) through the opening of the purinergic receptor/channel P2X7. On the other hand, P18 inhibits the Ca(2+) influx induced by 0.6 mm ATP in HEK293 cells stably transfected with P2X7, with an IC(50) of approximately 1 mum. Thus, P18 is devoid of intrinsic P2X7 stimulatory activity and behaves as an ATP antagonist. A P2X7-mediated increase of the basal [Ca(2+)](i) has been demonstrated to negatively affect Schwann cell (SC) function in rats with the inherited, peripheral neuropathy Charcot-Marie-Tooth 1A (CMT1A) (Nobbio, L., Sturla, L., Fiorese, F., Usai, C., Basile, G., Moreschi, I., Benvenuto, F., Zocchi, E., De Flora, A., Schenone, A., and Bruzzone S. (2009) J. Biol. Chem. 284, 23146-23158). Preincubation of CMT1A SC with 200 nm P18 restored the basal [Ca(2+)](i) to values similar to those recorded in wild-type SC. These results identify P18 as a new P2X7 antagonist, potentially useful in the treatment of CMT1A
Mitochondrial dysfunction induced by a cytotoxic adenine dinucleotide produced by ADP-ribosyl cyclases from cADPR
No full textADP-ribosyl cyclases were previously shown to produce three new adenine dinucleotides, P1,P2 diadenosine 5'-diphosphate (Ap2A) and two isomers thereof (P18 and P24), from cyclic ADP-ribose (cADPR) and adenine (Basile, G., Taglialatela-Scafati, O., Damonte, G., Armirotti, A., Bruzzone, S., Guida, L., Franco, L., Usai, C., Fattorusso, E., De Flora, A., and Zocchi, E. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 14509-14514). The Ap2A isomer P24, containing an unusual C1'-N3 N-glycosidic bond, is shown here to affect mitochondrial function through (i) opening of the permeability transition pore complex (and consequent proton gradient dissipation) and (ii) inhibition of Complex I of the respiratory chain. Whereas proton gradient dissipation is dependent upon the extracellular Ca(2+) influx triggered by P24, the effect on oxygen consumption is Ca(2+) independent. The proton gradient dissipation induces apoptosis in HeLa cells and thus appears to be responsible for the already described potent cytotoxic effect of P24 on several human cell types. The other products of ADP-ribosyl cyclase activity, Ap2A and cADPR, antagonize P24-induced proton gradient dissipation and cytotoxicity, suggesting that the relative concentration of P24, cADPR, and Ap2A in cyclase-positive cells may affect the balance between cell life and death
Patch-clamp recordings in isolated sponge cells (Axinella polypoides)
No full textSponges are the most ancient known metazoans. Their cells are specialised but not organised into tissues or organs. Recordings of action potential-like propagating electrical impulses suggested that electrical signalling may occur between sponge cells, but the characterization of ionic channels in these cells is still at the beginning. Actually, sponge cell surfaces are covered by a complex glycocalyx and long-chain fatty acids are present in the lipid core of their membranes. In these experimental conditions, a low percentage of tight seals (3%) was obtained applying the patch-clamp technique to cells isolated from the Mediterranean Demospongia Axinella polypoides. This paper shows in detail how difficulties can be overcome making use of trivalent cations in the extracellular solution and how electrophysiological measurements can be performed on sponge cell membranes. A potassium selective conductance is shown as an example. We suggest that the presented methodology could also be applied to other cell types
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
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