1,721,172 research outputs found

    Differential interactions of bacterial lipopolysaccharides with lipid membranes: implications for TRPA1-mediated chemosensation

    No full text
    Bacterial lipopolysaccharides (LPS) activate the TRPA1 cation channels in sensory neurons, leading to acute pain and inflammation in mice and to aversive behaviors in fruit flies. However, the precise mechanisms underlying this effect remain elusive. Here we assessed the hypothesis that TRPA1 is activated by mechanical perturbations induced upon LPS insertion in the plasma membrane. We asked whether the effects of different LPS on TRPA1 relate to their ability to induce mechanical alterations in artificial and cellular membranes. We found that LPS from E. coli, but not from S. minnesota, activates TRPA1. We then assessed the effects of these LPS on lipid membranes using dyes whose fluorescence properties change upon alteration of the local lipid environment. E. coli LPS was more effective than S. minnesota LPS in shifting Laurdan's emission spectrum towards lower wavelengths, increasing the fluorescence anisotropy of diphenylhexatriene and reducing the fluorescence intensity of merocyanine 540. These data indicate that E. coli LPS induces stronger changes in the local lipid environment than S. minnesota LPS, paralleling its distinct ability to activate TRPA1. Our findings indicate that LPS activate TRPA1 by producing mechanical perturbations in the plasma membrane and suggest that TRPA1-mediated chemosensation may result from primary mechanosensory mechanisms.We thank M. Benoit for excellent technical assistance, the members of the LICR for helpful discussions and Prof. C. Ulens for allowing the use of the Nanion Vesicle Prep Pro setup. Te CHO-mTRPA1 cell line was kindly provided by Dr. Ardem Patapoutian (Te Scripps Research Institute, USA). We would like to thank the Cell Imaging Core facility of the KU Leuven (http://gbiomed.kuleuven.be/english/corefacilities/microscopy/cic/cic. htm) for the use of the confocal microscope. Tis work was supported by grants of the Research Council of the KU Leuven (GOA/14/011) and the Fund for Scientifc Research Flanders (FWO: G070212N, G0C7715N and G0D0417N). Y.A.A. is a Postdoctoral Fellow of the FW

    The Readily Releasable Pool of Vesicles in Chromaffin Cells Is Replenished in a Temperature-Dependent Manner and Transiently Overfills at 37°C

    No full text
    Maturation of exocytic vesicles to the release-ready state is regulated by several factors, including intracellular calcium concentration ([Ca2+]int) and the state of protein phosphorylation. Here we investigated the effects of temperature on the recovery from depletion of the readily releasable pool (RRP) of vesicles in adrenal chromaffin cells. Exocytosis and [Ca2+]intwere monitored by combined membrane capacitance and fura-2 measurements. At higher temperatures, a faster pool refilling and a larger RRP size were observed. The time constants of the recovery from depletion ranged from 3.6 to 1.1 sec (22 and 37°C, respectively) yielding aQ10of 2.3. The changes of the Ca2+signal between the different temperatures could not account for the differences in recovery kinetics. At 32 and 37°C, we observed a transient overfilling of the RRP after pool depletion, which stands in clear contrast to the sustained secretory depression seen at lower temperatures. The overshoot in RRP size was very prominent in cells with lower basal [Ca2+]int, hence with a large difference between prestimulus and poststimulus [Ca2+]int. In cells with higher basal [Ca2+]int, the pool was larger under steady-state conditions but showed less overfilling on stimulation. We conclude that vesicle maturation is markedly accelerated at physiological temperature, thus allowing for a rapid adaptation of the pool size to the relatively short-lived Ca2+transient.</jats:p

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The 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 link
    We 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 link
    We 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

    Author Index

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    We 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

    The role of TRP channels in noxious heat sensing

    No full text
    Although several members of the transient receptor potential (TRP) superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. In the first part of this thesis, we developed, compared, and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channels in trigeminal and individual dorsal root ganglia from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1, and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8, and TRPV1, showed statistically significant variation in mRNA levels between dorsal root ganglia from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. This study provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family. Furthermore, although it is well-known that acute heat sensing in mammals is performed by a subset of sensory neurons expressing the heat sensor TRPV1, genetic ablation of TRPV1 or other candidate heat sensors, such as TRPM3, only resulted in small deficits in noxious heat sensing. So, the molecular basis of noxious heat sensing remained largely unresolved. In the second part of this thesis, we demonstrate that acute noxious heat sensing is mediated by a set of three TRP ion channels. We compared the sensitivity to heat in wild type mice and mice deficient for TRPV1, TRPM3, and TRPA1 in combined knockouts. We found that all double knockout mice retain robust heat responses at the cellular and behavioural level. In contrast, Trpa1-/-/Trpm3-/-/Trpv1-/- mice lack heat responses in isolated sensory neurons, and show a striking deficit in the heat sensitivity of intact C and Aδ nerve fibres and in the nociceptive responses to painfully hot temperatures. Reintroducing any of the three TRP channels into triple knockout sensory neurons restores heat responsiveness. Together, these data indicate that TRPA1, TRPV1, and TRPM3 have critical but redundant roles in acute noxious heat sensing. This redundancy could be a fail-safe mechanism allowing heat avoidance, even when the function of one or two molecular heat sensors is compromised.status: Publishe
    corecore