97 research outputs found

    Acute alcohol tolerance is intrinsic to the BKCa protein, but is modulated by the lipid environment

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    Ethanol tolerance, in which exposure leads to reduced sensitivity, is an important component of alcohol abuse and addiction. The molecular mechanisms underlying this process remain poorly understood. The BKCa channel plays a central role in the behavioral response to ethanol in Caenorhabditis elegans (Davies, A. G., Pierce-Shimomura, J. T., Kim, H., VanHoven, M. K., Thiele, T. R., Bonci, A., Bargmann, C. I., and McIntire, S. L. (2003) Cell 115, 655-666) and Drosophila (Cowmeadow, R. B., Krishnan, H. R., and Atkinson, N. S. (2005) Alcohol. Clin. Exp. Res. 29, 1777-1786) . In neurons, ethanol tolerance in BKCa channels has two components: a reduced number of membrane channels and decreased potentiation of the remaining channels (Pietrzykowski, A. Z., Martin, G. E., Puig, S. I., Knott, T. K., Lemos, J. R., and Treistman, S. N. (2004) J. Neurosci. 24, 8322-8332) . Here, heterologous expression coupled with planar bilayer techniques examines two additional aspects of tolerance in human BKCa channels. 1) Is acute tolerance observed in a single channel protein complex within a lipid environment reduced to only two lipids? 2) Does lipid bilayer composition affect the appearance of acute tolerance? We found that tolerance was observable in BKCa channels in membrane patches pulled from HEK cells and when they are placed into reconstituted 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine/1-palmitoyl-2-o leoyl-sn-glycero-3-phosphatidylserine membranes. Furthermore, altering bilayer thickness by incorporating the channel into lipid mixtures of 1,2-dioleoyl-3-phosphatidylethanolamine with phosphatidylcholines of increasing chain length, or with sphingomyelin, strongly affected the sensitivity of the channel, as well as the time course of the acute response. Ethanol sensitivity changed from a strong potentiation in thin bilayers to inhibition in thick sphingomyelin/1,2-dioleoyl-3-phosphatidylethanolamine bilayers. Thus, tolerance can be an intrinsic property of the channel protein-lipid complex, and bilayer thickness plays an important role in shaping the pattern of response to ethanol. As a consequence of these findings the protein-lipid complex should be treated as a unit when studying ethanol action

    Somatic localization of a specific large-conductance calcium-activated potassium channel subtype controls compartmentalized ethanol sensitivity in the nucleus accumbens

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    Alcohol is an addictive drug that targets a variety of ion channels and receptors. To address whether the effects of alcohol are compartment specific (soma vs dendrite), we examined the effects of ethanol (EtOH) on large-conductance calcium-activated potassium channels (BK) in cell bodies and dendrites of freshly isolated neurons from the rat nucleus accumbens (NAcc), a region known to be critical for the development of addiction. Compartment-specific drug action was indeed observed. Clinically relevant concentrations of EtOH increased somatic but not dendritic BK channel open probability. Electrophysiological single-channel recordings and pharmacological analysis of the BK channel in excised patches from each region indicated a number of differences, suggestive of a compartment-specific expression of the beta4 subunit of the BK channel, that might explain the differential alcohol sensitivity. These parameters included activation kinetics, calcium dependency, and toxin blockade. Reverse transcription-PCR showed that both BK channel beta1 and beta4 subunit mRNAs are found in the NAcc, although the signal for beta1 is significantly weaker. Immunohistochemistry revealed that beta1 subunits were found in both soma and dendrites, whereas beta4 appeared restricted to the soma. These findings suggest that the beta4 subunit may confer EtOH sensitivity to somatic BK channels, whereas the absence of beta4 in the dendrite results in insensitivity to the drug. Consistent with this idea, acute EtOH potentiated alphabeta4 BK currents in transfected human embryonic kidney cells, whereas it failed to alter alphabeta1 BK channel-mediated currents. Finally, an EtOH concentration (50 mm) that increased BK channel open probability strongly decreased the duration of somatic-generated action potential in NAcc neurons

    ESABALT - Improvement of Situational Awareness in the Baltic with the Use of Crowdsourcing

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    This paper presents the key assumptions and preliminary research on an integrated system called ESABALT, for enhancing maritime safety, which incorporates the latest technological advances in positioning, e-Navigation, Earth observation systems and multi-channel cooperative communications. The most novel part of the ESABALT concept, however, is a focus on user-driven crowdsourcing techniques for information gathering and integration. The system will consist of a situational awareness solution for real-time maritime traffic monitoring via utilizing various positioning technologies; an observation system of the marine environment relevant to transportation and accidents including assessing the sea ice, oil spread, waves, wind etc.; and a methodology for context-aware maritime communication with cooperative, multi-channel capabilities. The paper presents the intelligent, novel, user-driven solution and associated services developed in ESABALT for enhancing the maritime safety in the whole Baltic area

    A global spectral library to characterize the world's soil

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    Soil provides ecosystem services, supports human health and habitation, stores carbon and regulates emissions of greenhouse gases. Unprecedented pressures on soil from degradation and urbanization are threatening agro-ecological balances and food security. It is important that we learn more about soil to sustainably manage and preserve it for future generations. To this end, we developed and analyzed a global soil visible-near infrared (vis-NIR) spectral library. It is currently the largest and most diverse database of its kind. We show that the information encoded in the spectra can describe soil composition and be associated to land cover and its global geographic distribution, which acts as a surrogate for global climate variability. We also show the usefulness of the global spectra for predicting soil attributes such as soil organic and inorganic carbon, clay, silt, sand and iron contents, cation exchange capacity, and pH. Using wavelets to treat the spectra, which were recorded in different laboratories using different spectrometers and methods, helped to improve the spectroscopic modelling. We found that modelling a diverse set of spectra with a machine learning algorithm can find the local relationships in the data to produce accurate predictions of soil properties. The spectroscopic models that we derived are parsimonious and robust, and using them we derived a harmonized global soil attribute dataset, which might serve to facilitate research on soil at the global scale. This spectroscopic approach should help to deal with the shortage of data on soil to better understand it and to meet the growing demand for information to assess and monitor soil at scales ranging from regional to global. New contributions to the library are encouraged so that this work and our collaboration might progress to develop a dynamic and easily updatable database with better global coverage. We hope that this work will reinvigorate our community's discussion towards larger, more coordinated collaborations. We also hope that use of the database will deepen our understanding of soil so that we might sustainably manage it and extend the research outcomes of the soil, earth and environmental sciences towards applications that we have not yet dreamed of

    Poster display II clinical general

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    Influences de la sylviculture sur le risque de dégâts biotiques et abiotiques dans les peuplements forestiers

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    Safe Ship Trajectory Determination in the ENC Environment

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    Operations of maritime autonomous surface ships

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    Advancing technologies create unique opportunities for constructing autonomous ships, which, in turn, raise growing interest of the maritime industry, shipowners in particular. These authors have analyzed actions taken in this field and some aspects related to the operations of maritime autonomous surface ships (MASS). The presented case study refers to a ship with a skeleton crew on a deep sea voyage, where the ship’s autonomy is narrowed to the fourth stage of transport task – sea voyage and its navigational aspect

    Safety of Navigation in a Restricted Area - the Fuzzy Domain of Various Size Ships

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    Parametry statku są istotnym czynnikiem uwzględnianym w ocenie sytuacji nawigacyjnej na akwenie ograniczonym w aspekcie bezpieczeństwa nawigacji. Jednym z kryteriów oceny jest rozmyta domena statku. Podstawą do jej wyznaczenia jest pozyskanie i reprezentacja wiedzy nawigatorów z wykorzystaniem metod i narzędzi sztucznej inteligencji. W artykule przedstawiono wyniki badań i wstępną analizę wpływu wielkości statku na kształt i rozmiar domeny rozmytej.Ship's parameters are an essential factor taken into consideration when ship's safety is assessed in a navigational situation in a restricted area. The ship's fuzzy domain is one of the assessment criteria. Its determination is based on the representation of previously acquired navigators' knowledge combined with methods and tools of artificial intelligence. This article presents research results and a preliminary analysis of how a ship's size affects the shape and size of its fuzzy domain
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