1,721,004 research outputs found
pH<sub>i</sub> and serum regulate AE2-mediated Cl<sup>Ő</sup>/HCO<sup>Ő</sup><sub>3</sub>, exchange in CHOP cells of defined transient transfection status
No full text Page C855: L. Jiang, A. Stuart-Tilley, J. Parkash, and S. L. Alper. “pHi and serum regulate AE2-mediated Cl-/HCO-3, exchange in CHOP cells of defined transient transfection status.” The acknowledgment section omitted our thanks to Genetics Institute and Dana Dubois for subsidizing the additional cost of publication in color. </jats:p
pH<sub>i</sub>and serum regulate AE2-mediated Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup>, exchange in CHOP cells of defined transient transfection status
No full textPage C855: L. Jiang, A. Stuart-Tilley, J. Parkash, and S. L. Alper. “pHi and serum regulate AE2-mediated Cl-/HCO3-, exchange in CHOP cells of defined transient transfection status.” The acknowledgment section omitted our thanks to Genetics Institute and Dana Dubois for subsidizing the additional cost of publication in color.</jats:p
Ca(2+)-activated K+ transport in erythrocytes. Comparison of binding and transport inhibition by scorpion toxins
No full textWe have investigated the interactions of synthetic charybdotoxin (ChTX), synthetic iberiotoxin (IbTX), and recombinant mutant ChTX peptides with the Ca(2+)-activated K+ channel (Gardos pathway) in human and rabbit erythrocytes. We measured the binding of 125I-ChTX to erythrocytes, the displacement of bound 125I-ChTX by unlabeled toxin and analogs, and then compared these data with isotopic and electrical indices of channel activity measured under the same conditions. We found that a major portion of 125I-ChTX bound to red cells was displaceable by excess unlabeled ChTX. This specific 125I-ChTX binding to human red cells was markedly increased in low ionic strength conditions as compared with that measured at physiological ionic strength and at alkaline pH as compared with normal pH. At pH 8 and low ionic strength, specific binding could be described most simply as a single class of sites of Kd = 94 +/- 49 pM and Bmax = 120 +/- 36 sites/cell (n = 3). Ca(2+)-activated 86Rb influx measured under identical conditions revealed an ID50 for ChTX of 21 +/- 15 pM (n = 6) at low ionic strength and 4 +/- 2.4 nM (n = 4) at physiological ionic strength. Similar studies in rabbit erythrocytes at low ionic strength revealed a Kd for 125I-ChTX = 37 +/- 17 pM, with 126 +/- 24 binding sites/cell and an ID50 for inhibition of 86Rb influx by ChTX = 25 pM. Whereas IbTX neither inhibited Ca(2+)-activated 86Rb influx nor displaced 125I-ChTX in human red cells, it partially displaced 125I-ChTX and partially inhibited 86Rb influx in rabbit red cells. Studies with recombinant mutant ChTX peptides showed that the mutant toxin K27Q was inactive as a transport inhibitor and displayed a large reduction in ability to displace 125I-ChTX. The mutation K31Q resulted in abolition of ionic strength dependence of the inhibitory effect on the Ca(2+)-activated K+ permeability. In view of the similarity between the 125I-ChTX binding constant and the transport inhibition constant of ChTX, we examined the potency of 125I-ChTX as a transport inhibitor. 125I-ChTX inhibited Ca(2+)-activated K+ transport with ID50 values of 3.3 +/- 1 nM (n = 7) at low ionic strength and 4.1 +/- 3 nM (n = 6) at physiologic ionic strength. Thus, at physiologic ionic strength 125I-ChTX and ChTX are indistinguishable as inhibitors of erythroid Ca(2+)-activated K+ transport. However, iodination of Y36 is associated with abolition of the 200-fold increase in inhibitory potency shown by ChTX at low ionic strength
Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives [see comments]
No full textWe have investigated the interaction of clotrimazole (CLT) and related compounds with the erythroid Ca(2+)-activated K+ channel, a mediator of sickle cell dehydration. We measured K+ transport, membrane potential, and cell volume upon activation of this pathway in sickle erythrocytes. CLT blocked almost completely Ca(2+)-activated K+ transport in homozygous hemoglobin S cells, with IC50 values of 29 +/- 15 nM in isotonic 20 mM salt solution and 51 +/- 15 nM in normal saline (n = 3). The inhibition of K+ transport by CLT was caused by a specific interaction with the Ca(2+)-activated K+ channel of human red cells, since it displaced bound 125I-Charybdotoxin, a specific ligand of the Gardos channel, with an IC50 (12 +/- 4 nM in isotonic 20 mM) similar to the IC50 values for flux inhibition. When homozygous hemoglobin S cells were dehydrated by incubation in the presence of 100 microM CaCl2 and the ionophore A23187, or by exposure to cycles of oxygenation and deoxygenation, CLT effectively inhibited cell dehydration and K+ loss. The IC50 of CLT for inhibition of Ca(2+)-activated K+ transport in sickle cells is significantly lower than plasma concentrations of CLT achievable after nontoxic oral doses. We therefore propose that oral administration of CLT may prevent red cell dehydration in patients with sickle cell anemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Treatment with oral clotrimazole blocks Ca(2+)-activated K+ transport and reverses erythrocyte dehydration in transgenic SAD mice. A model for therapy of sickle cell disease.
No full textPrevention of red cell K+ and water loss is a therapeutic strategy for sickle cell disease. We have investigated in vitro and in vivo the effects of clotrimazole (CLT) and miconazole (MIC) on transgenic mice red cells expressing hemoglobin SAD. CLT blocked the Gardos channel (ID50 75 +/- 22 nM; n = 3) and the A23187-induced dehydration of Hbbs/Hbbthal SAD 1 mouse erythrocytes in vitro. Oral treatment with CLT (160 mg/kg per d) and MIC (100 mg/kg per d) inhibited the Gardos channel in both SAD 1 and control (Hbbs/Hbbthal) mice. In the SAD 1 mice only, cell K+ content increased, and mean corpuscular hemoglobin concentration and cell density decreased. After 7 d of treatment, the hematocrit of SAD 1, CLT-treated animals also increased. All changes were fully reversible. Long-term treatments of SAD 1 mice with oral CLT (80 mg/kg per d for 28 d) lead to sustained increases in cell K+ content and hematocrit and sustained decreases in mean corpuscular hemoglobin concentration and cell density, with no changes in animals treated with vehicle alone. Thus, CLT and MIC can reverse dehydration and K+ loss of SAD 1 mouse erythrocytes in vitro and in vivo, further supporting the potential utility of these drugs in the treatment of sickle cell anemia
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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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