1,721,084 research outputs found
Physical methods to quantify small antibiotic molecules uptake into Gram-negative bacteria
No full textThe development of antibiotics against Gram-negative bacteria is a challenge: any active compound must cross the outer cell envelope composed of a hydrophilic highly charged lipopolysaccharide layer followed by a tight hydrophobic layer containing water filled gates called porins to reach the hydrophilic periplasmic space and depending on the target with the further need to cross the hydrophobic inner membrane. In addition to a possible rapid enzymatic deactivation efflux pumps shuffle compounds back outside. The resulting low permeability of cell envelope requires high dose and leads therefore to toxicity problems. Despite its relevance the permeability barrier in Gram-negative bacteria is not well understood partially caused by the lack of appropriate direct assays. Here we give a brief introduction on current available techniques to quantify passive diffusion of small hydrophilic molecules into Gram-negative bacteri
Antibiotic Permeation across the OmpF Channel: Modulation of the Affinity Site in the Presence of Magnesium
No full textWe characterize the rate-limiting interaction of the antibiotic
10 enrofloxacin with OmpF, a channel from the outer cell wall of Escherichia coli.
11 Reconstitution of a single OmpF trimer into planar lipid membranes allows
12 measurement of the ion current through the channel. Penetration of antibiotics causes
13 ion current blockages, and their frequency allows a conclusion on the kinetics of
14 channel entry and exit. In contrast to other antibiotics, enrofloxacin is able to block the
15 OmpF channel for several milliseconds, reflecting high affinities comparable to
16 substrate-specific channels such as the maltodextrin-specific maltoporin. Surprisingly,
17 the presence of a divalent ion such as Mg2+ leads to fast flickering with an increase in
18 the rates of association and dissociation. All-atom computer modeling provides the
19 most probable pathway able to identify the relevant rate-limiting interaction during antibiotic permeation. Mg2+ has a high affinity
20 for the aspartic acid at the 113 position (D113) in the center of the OmpF intracellular binding site. Therefore, the presence of Mg2+
21 reverses the charge and enrofloxacin may cross the constriction region in its favorable orientation with the carboxylic group first
Analysis of fast channel blockage: revealing substrate binding in the microsecond range
No full textFor an antibiotic to be effective, it needs to cross the outer membrane barrier and reach the target inside
the cell. Hydrophilic antibiotics, e.g. β-lactams, use porin channels to cross the outer membrane and
accumulate in the periplasm. Experimental determination of antibiotic interactions with porin is performed
by using electrophysiology on a single channel level by noise analysis or single event analysis methods.
We report a novel framework for analyzing the ion-current noise, taking into account the corrections
due to the analogous filter and the sampling procedure, with the goal of extending the time resolution
to a range previously inaccessible by event analysis or by conventional noise analysis. The new method
allows one to analyse fast binding events and/or the case when the single channel is not completely
blocked by the substrate. We demonstrate the power of this approach by using as an example the interactions
of meropenem, an antibiotic of the carbapenem family, with the OmpF porin that is considered
to be one of the main pathways for antibiotics to enter Escherichia coli. The presence of meropenem in
OmpF is detected by ion current blockages, and the on and off rates are estimated from the concentration
dependence of the average ion current and of its power spectral density. The obtained average
residence time of the antibiotic inside the channel is in the range of a few microseconds, i.e. more than
50 times smaller than the inverse cut-off frequency of the analogous filter
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
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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