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Chloride conductance activated by external agonists and internal messengers in rat peritoneal mast cells
Full text linkStimulation of mast cells by externally applied secretagogues activated a slowly developing membrane current. With high external and low internal chloride (Cl-) concentrations, the current reversed at about -40 mV, but when external Cl- was made equal to internal Cl-, the reversal potential shifted to about 0 mV, demonstrating that the current carrier was Cl-. 2. In addition to external agonists, internally applied cyclic AMP and high concentrations of intracellular calcium [Ca2+]i could also activate the Cl- current. However, elevated [Ca2+]i produced only slow and incomplete activation. This suggests that the Cl- current is not directly Ca2+ activated. Also, activation of Cl- current by external agonists and by cyclic AMP was unimpaired when [Ca2+]i was clamped to low levels with internal ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA), indicating that elevated [Ca2+]i is not necessary for activation of the Cl- current. Although activation by cyclic AMP was faster than that produced by elevated [Ca2+]i, it still required tens of seconds; thus the effect of cyclic AMP was also likely to be indirect. 3. Internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) could also activate the Cl- current, suggesting the involvement of a G protein in the control of the current. 4. The variance associated with the Cl- current was small, and noise analysis gave a lower limit of about 1-2 pS for the single-channel conductance. The Cl- current was reduced by 4,4'-diisothiocyano-2,2'-stilbenedisulphonate (DIDS), and during DIDS blockade, the variance of the current increased. This suggests that DIDS enters and blocks the open channel. 5. Activation of the Cl- current would make the membrane potential negative following stimulation of a mast cell, thus providing a driving force for entry of external calcium via the stimulation-induced influx pathways described in the preceding paper (Matthews, Neher & Penner, 1989)
Second messenger-activated calcium influx in rat peritoneal mast cells
Full text linkTo study the regulation of calcium influx in non-excitable cells, membrane currents of rat peritoneal mast cells were recorded using the whole-cell patch-clamp technique. At the same time, intracellular calcium concentration ([Ca2+]i) was monitored via the fluorescent calcium-indicator dye Fura-2, which was loaded into cells by diffusion from the patch pipette. 2. Stimulation of mast cells with secretagogues, such as compound 48/80 or substance P, caused release of Ca2+ from internal stores. In addition, external agonists also induced influx of external calcium in 26% of the cells investigated. The agonist-stimulated Ca2+ influx was increased during membrane hyperpolarization and was associated with small whole-cell currents. 3. Likewise, internal application of inositol 1,4,5-trisphosphate (Ins1,4,5P3:0.5-10 microM) elevated [Ca2+]i due both to release of Ca2+ from internal stores and to influx of external calcium. The Ins1,4,5P3-induced influx was greater at more negative membrane potentials, suggesting that Ins1,4,5P3 opened a pathway through which calcium could enter at a rate governed by its electrochemical driving force. 4. Inositol 1,3,4,5-tetrakisphosphate (Ins1,3,4,5P4) did not induce Ca2+ influx by itself nor did it facilitate or enhance Ins1,4,5P3-induced Ca2+ entry. Calcium influx was also induced by inositol 2,4,5-trisphosphate. Since this inositol phosphate is a poor substrate for Ins1,4,5P3 3-kinase it seems unlikely that Ins1,3,4,5P4 plays a role in the regulation of the Ca2(+)-influx pathway in mast cells. 5. The Ins1,4,5P3-induced Ca2+ influx was associated with whole-cell currents of 1-2 pA or less, with no channel activity detectable in whole-cell recordings. The small size of the whole-cell current suggests either that the Ins1,4,5P3-dependent influx occurs via small-conductance channels that are highly calcium specific or that the influx is not via ion channels. 6. Agonist stimulation also activated large-conductance (ca 50 pS) cation channels, through which divalent cations could permeate; thus, these channels represent a second pathway for Ca2+ influx. The slow speed of activation of the channels by agonists, their activation by internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), and the inhibition of agonist activation by internal guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) all suggest that the 50 pS channels are regulated by a second messenger and/or a GTP-binding protein. The activity of the 50 pS channel in mast cells is not sensitive to either Ins1,4,5P3 or Ins1,3,4,5P4. Activity of the channel was inhibited by elevated [Ca2+]
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
Novel chloride conductance in the membrane of bovine chromaffin cells activated by intracellular GTP gamma S.
Full text linkThe effects of introducing the non-hydrolysable GTP analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) into perfused bovine chromaffin cells were studied by a combination of the tight-seal whole-cell patch-clamp technique and Fura-2 fluorescence [Ca2+]i measurements. 2. GTP gamma S (5-300 microM) induced a slowly developing transient current (inwardly directed at the holding potential -60 to -70 mV) and [Ca2+]i oscillations. The current activated with a 10-50 s delay after the start of whole-cell dialysis, peaked at 70-120 s and decayed almost to its initial level during the next 150-300 s. Calcium oscillations were observed within the first 100-150 s of cell perfusion. 3. GTP competitively lowered the probability of current activation by GTP gamma S. At low GTP gamma S/GTP ratio (5 and 300 microM, respectively) activation of the current was observed only rarely. 4. The activation of the current was accompanied by an increase in conductance but not by changes in the current reversal potential. The changes in the conductance did not depend on the membrane potential; no time-dependent relaxation of the current was induced by steps in the membrane voltage. 5. The current reversal potential was close to the Cl- equilibrium potential; changes in the extracellular Cl- concentration induced corresponding changes in the current amplitude and shifted its reversal potential. The permeability to larger anions--aspartate, glutamate and isethionate--was about one-tenth of that for chloride. 6. Single-channel conductance, estimated from the ratio of the mean current and its variance, was about 1-2 pS. 7. The current could be reversibly blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS, 10 microM), chlorpromazine (5 microM) and tolbutamide (0.5-5 mM). 8. It is suggested that the GTP gamma S-induced increase in the permeability to Cl- ions is due to a G protein-mediated production of an as yet unidentified second messenger
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
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