1,721,005 research outputs found
A comparison of electrophysiological properties of the CNGA1, CNGA1tandem and CNGA1cys-free channels.
No full textItem does not contain fulltextThree constructs are used for the analysis of biophysical properties of CNGA1 channels: the WT CNGA1 channel, a CNGA1 channel where all endogenous cysteines were removed (CNGA1cys-free) and a construct composed of two CNGA1 subunits connected by a small linker (CNGA1tandem). So far, it has been assumed, but not proven, that the molecular structure of these ionic channels is almost identical. The I/V relations, ionic selectivity to alkali monovalent cations, blockage by tetracaine and TMA+ were not significantly different. The cGMP dose response and blockage by TEA+ and Cd2+ were instead significantly different in CNGA1 and CNGA1cys-free channels, but not in CNGA1 and CNGA1tandem channels. Cd2+ blocked irreversibly the mutant channel A406C in the absence of cGMP. By contrast, Cd2+ did not block the mutant channel A406C in the CNGA1cys-free background (A406Ccys-free), but an irreversible and almost complete blockage was observed in the presence of the cross-linker M-4-M. Results obtained with different MTS cross-linkers and reagents suggest that the 3D structure of the CNGA1cys-free differs from that of the CNGA1 channel and that the distance between homologous residues at position 406 in CNGA1cys-free is longer than in the WT CNGA1 by several Angstroms
The analysis of desensitizing CNGA1 channels reveals molecular interactions essential for normal gating
Full text linkGating in CNGA1 channels
No full textThe aminoacid sequences of CNG and K(+) channels share a significant sequence identity, and it has been suggested that these channels have a common ancestral 3D architecture. However, K(+) and CNG channels have profoundly different physiological properties: indeed, K(+) channels have a high ionic selectivity, their gating strongly depends on membrane voltage and when opened by a steady depolarizing voltage several K(+) channels inactivate, whereas CNG channels have a low ion selectivity, their gating is poorly voltage dependent, and they do not desensitize in the presence of a steady concentration of cyclic nucleotides that cause their opening. The purpose of the present review is to summarize and recapitulate functional and structural differences between K(+) and CNG channels with the aim to understand the gating mechanisms of CNG channels
Movement of the C-Helix during the Gating of Cyclic Nucleotide-Gated Channels
No full textAbstractMovements within the cyclic nucleotide-binding domain of cyclic nucleotide-gated channels are thought to underlie the initial phase of channel gating (Tibbs, G. R., D. T. Liu, B. G. Leypold, and S. A. Siegelbaum. 1998. J. Biol. Chem. 273:4497–4505; Zong, X., H. Zucker, F. Hofmann, and M. Biel. 1998. EMBO J. 17:353–362; Matulef, K., G. E. Flynn, and W. N. Zagotta. 1999. Neuron. 24:443–452; Paoletti, P., E. C. Young, and S. A. Siegelbaum. 1999. J. Gen. Physiol. 113:17–33; Johnson, J. P., and W. N. Zagotta. 2001. Nature. 412:917–921). To investigate these movements, cysteine mutation was performed on each of the 28 residues (Leu-583 to Asn-610), which span the agonist-binding domain of the α-subunit of the bovine rod cyclic nucleotide-gated channel. The effects of Cd2+ ions, 2-trimethylammonioethylmethane thiosulfonate (MTSET) and copper phenanthroline (CuP) on channel activity were examined, in excised inside-out patches in the presence and in the absence of a saturating concentration of cGMP. The application of 100μM Cd2+ in the presence of saturating concentration of cGMP caused an irreversible and almost complete reduction of the current in mutant channels E594C, I600C, and L601C. In the absence of cGMP, the presence of 100μM Cd2+ caused a strong current reduction in all cysteine mutants from Asp-588 to Leu-607, with the exception of mutant channels A589C, M592C, M602C, K603C, and L606C. The selective effect of Cd2+ ions was very similar to that observed when adding the oxidizing agent CuP to the bath medium, except for mutant channel G597C, where CuP caused a stronger current decrease (67±7%) than Cd2+ (23±4%). In the absence of cGMP, MTSET caused a reduction of the current by >40% in mutant channels L607C, L601C, I600C, G597C, and E594C, whereas in the presence of cGMP only mutant channel L601C was affected. The application of MTSET protected many mutant channels from the effects of Cd2+ and CuP. These results suggest that, when CNG channels are in the open state, residues from Asp-588 to Leu-607 are in an α-helical structure, homologous to the C-helix of the catabolite gene activator protein (Weber, I. T., and T. A. Steitz. 1987. J. Mol. Biol. 198:311–326). Furthermore, residues Glu-594, Gly-597, Ile-600, and Leu-601 of these helices belonging to two different subunits must be in close proximity. In the closed state the C-helices are in a different configuration and undergo significant fluctuations
Adecision support systemfor industrial waste heat recovery: the CE-HEAT Project
No full textThe exploitation of the huge potential for industrial waste heat recovery detected in Europe represents an opportunity to accomplish the objectives set by the European Union with the aim to reduce resources consumption, greenhouse gases emissions and to fightclimate change. The CE-HEAT project, financed by the Interreg Central Europe Programme, aims to improve the governance of energy efficiency by focusing on the field of waste heat utilization in Central Europe space. In order to aid the decision-making process of investors and policy makers, an online decision support tool for the preliminary assessment of investments in waste heat recovery projects has been implemented. Different operating scenarios could be compared combining various heat recovery technologies, some of which considering single companies (absorption chiller, heat exchanger, heat pump) and others network oriented (district heating, ORC). The operation of the online tool is based on a multi-objective decision support system (DSS) which hasbeen specifically developed. The objective functions evaluate environmental impact minimization and economic performances maximization, ensuring a sustainability analysis. In order to evaluate the main parameters that interest the stakeholders, decision variables such as incentives, grant, thermal and electrical energy costs have been considered. The developed DSS is aimed at helping final users in the decision-making process through a conscious comparison between different waste heat recovery options based on the exploitation of different technologies. Once the input variables are selected by the user, the program will provide the decision support suggestions in terms of sustainability performance indicators, displayed by graphs and tables, allowing a comparison of these option
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
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