1,721,019 research outputs found
Semisynthetic derivatives of concanamycin A and C, as inhibitors of V- and P-type ATPases: Structure-activity investigations and developments of photoaffinity probes
No full textV-type ATPases are inhibited by the plecomacrolides bafilomycin and concanamycin, which exert their inhibitory potential at nanomolar concentrations. In addition, some P-type ATPases are inhibited at micromolar concentrations. We initiated intensive structure-activity investigations with semisynthetic concanamycin derivatives to approach the following two questions: (i) What is the pharmacophor, the structural key element, of the plecomacrolides that leads to their inhibitory potential against V- and P-type ATPases? (ii) Where is the binding site within these two different types of ATPases? In a first step, we examined where chemical modifications (O-acylations, substitutions, eliminations) could be placed without seriously affecting the inhibitory potential of the macrolides. In a second step, we used the knowledge of these structure-activity investigations to introduce traceable elements (fluorescent or radioactive) or nitrene-generating azido or carbene-generating diazirine-groups able to bind the inhibitors to their target covalently. These studies led finally to the synthesis of two photoaffinity probes that were used in labeling experiments with the purified plasma membrane V-type ATPase of Manduca sexta (described in a following paper, Huss, M., Gassel, M., Ingenhorst, G., Drose, S., Zeeck, A., Altendorf, K., Wieczorek, H., manuscript submitted)
ATP Synthesis Catalyzed by the ATP Synthase of Escherichia coli Reconstituted into Liposomes
No full textThe H+‐translocating F0F1‐ATPase from Escherichia coli (EF0F1) was purified and reconstituted into preformed reverse‐phase liposomes prepared from egg yolk phosphatidylcholine/phosphatidic acid. The EF0F1 liposomes were energized by an acid/base transition (pHout= 8.3; pHin= 5.0) and a superimposed K+/valinomycin diffusion potential ([K+]out= 100 mM; [K+]in= 0.6 mM) yielding a maximum rate (turnover number) of ATP synthesis of 27±8 mol ATP · molEF0F1−1· s−1), i.e. 27±8 s−1 This reaction was inhibited by NH4Cl or by addition of the F0F1, inhibitor N,N′‐dicyclohexylcarbodiimide. The rate of ATP synthesis measured as a function of the phosphate and ADP concentrations, can be described by Michaelis‐Menten kinetics with a Km of 0.7±0.2 mM for phosphate ([ADP] = 200 μM) and a Km, of 27±7 μM for ADP ([phosphate] = 5 mM), respectively. Copyright © 1994, Wiley Blackwell. All rights reserve
Synthesis of a doubly labelled concanamycin derivative for ATPase binding studies
No full textThe synthesis of a doubly labelled concanamycin derivative for binding studies with V- and P-type ATPases is described. The starting point was 21-deoxyconcanolide A (6), which was generated from concanamycin A (1) in three steps and which exhibited the full ATPase inhibitor activity, with the advantage of a stability better than that of 1. Through use of a suitable protecting group for 6, the carbene-generating diazirine residue and I-125 were introduced regio- and stereo- selectively. The inhibitory efficacy of the resulting 23-iodo(I-125)-9-O-[p-(trifluoroethyldiazirinyl)benzoyl]-21,23- dideoxyconcanolide A (11b) turned out to be high enough for labelling studies. Photoaffinity labelling experiments clearly showed that 11b is a suitable derivative with which to determine the binding site of concanamycin-like compounds in different ATPases
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
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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