Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BK-beta-1-subunit leads to progressive hearing loss

The large conductance voltage- and Ca2+-activated potassium (BK) channel has been suggested to play an important role in the signal transduction process of cochlear inner hair cells. BK channels have been shown to be composed of the pore-forming alpha-subunit coexpressed with the auxiliary beta-1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha–/–) and beta-1-subunit (BKbeta-1–/–) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta-1–/– mice. During the first 4 postnatal weeks also, BKalpha–/– mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BKalpha–/– mice only from ca. 8 weeks postnatally onward and was accompanied by a lack of distortion product otoacoustic emissions, suggesting outer hair cell (OHC) dysfunction. Hearing loss was linked to a loss of the KCNQ4 potassium channel in membranes of OHCs in the basal and midbasal cochlear turn, preceding hair cell degeneration and leading to a similar phenotype as elicited by pharmacologic blockade of KCNQ4 channels. Although the actual link between BK gene deletion, loss of KCNQ4 in OHCs, and OHC degeneration requires further investigation, data already suggest human BK-coding slo1 gene mutation as a susceptibility factor for progressive deafness, similar to KCNQ4 potassium channel mutations. © 2004, The National Academy of Sciences. Freely available online through the PNAS open access option

Making open data work for plant scientists

Despite the clear demand for open data sharing, its implementation within plant science is still limited. This is, at least in part, because open data-sharing raises several unanswered questions and challenges to current research practices. In this commentary, some of the challenges encountered by plant researchers at the bench when generating, interpreting, and attempting to disseminate their data have been highlighted. The difficulties involved in sharing sequencing, transcriptomics, proteomics, and metabolomics data are reviewed. The benefits and drawbacks of three data-sharing venues currently available to plant scientists are identified and assessed: (i) journal publication; (ii) university repositories; and (iii) community and project-specific databases. It is concluded that community and project-specific databases are the most useful to researchers interested in effective data sharing, since these databases are explicitly created to meet the researchers’ needs, support extensive curation, and embody a heightened awareness of what it takes to make data reuseable by others. Such bottom-up and community-driven approaches need to be valued by the research community, supported by publishers, and provided with long-term sustainable support by funding bodies and government. At the same time, these databases need to be linked to generic databases where possible, in order to be discoverable to the majority of researchers and thus promote effective and efficient data sharing. As we look forward to a future that embraces open access to data and publications, it is essential that data policies, data curation, data integration, data infrastructure, and data funding are linked together so as to foster data access and research productivity

Vorbereitung der Evaluation während der Entwicklung des MANET-Systems im Bezug auf die Anwenderfreundlichkeit

Die Koordination von Großschadenslagen mit vielen Verletzten stellt die Verantwortlichen vor eine schwere Aufgabe. Gemeinsam mit anderen Partnern aus Wissenschaft und Industrie bearbeitet die Fachhochschule Köln das orschungsprojekt "Beherrschbarkeit von Katastrophenereignissen durch autonom vernetzte Sensoren (MANET)". Mit dem Ergebnis dieses Projekts soll die Koordination der Einsatzkräfte, der Fahrzeuge und des Materials verbessert werden, mit dem Ziel eine schnellere Patientenversorgung zu gewährleisten. Bisher existieren Prototypen des entwickelten Systems. Dieses wird in realitätsnahen Übungen, in denen Groÿschadenslagen dargestellt werden, von Einsatzkräften verwendet. Um die Anwenderfreundlichkeit des Systems zu ermitteln wurde eine Befragung konzipiert, mit der die Erfahrungen der Anwender nach der Übung ermittelt werden können. Im Vorlauf der Befragungserstellung wurden allgemeine Regeln zur Fragen- und Antwortgestaltung sowie Grundlagen zur Auswertung de niert. Die Befragung wird mithilfe eines elektronischen Befragungssystems durchgeführt, wodurch die Fragen und Antworten besondere Vorgaben zu erfüllen haben. Diese wurden bei der Erstellung der Fragen, zusätzlich zu den allgemeinen Regeln, berücksichtigt. Neben den Fragen wurden für die Befragung Umgebungsbedingungen de niert, die für eine erfolgreiche Durchführung notwendig sind. Gemeinsam mit den Fragen wurden diese Bedingungen in einem Fragebogen zusammengefasst, der den gesamten Ablauf der Befragung vorgibt. Durch diese Vorgabe ist eine Vergleichbarkeit von mehreren Befragungsdurchgängen gewährleistet

Multicolour STED nanoscopy with hyperspectral detection

Within the scope of this thesis, a new multicolour STED microscope with a hyperspectral detection was designed and built. The challenges regarding the limitation of usable fluorophores as well as the stability of the optical set-up were overcome. Different existing spectral unmixing methods were compared to a self-implemented algorithm, both in simulations and using experimental data. A detailed study of the best separation conditions for several dye combinations was carried out for each of the methods. During the experiments, a spectral blue shift of several dyes was observed and its mechanisms were investigated. The optical resolution of the set-up was dye dependent and better than 80nm for all dyes. Moreover, an excellent separation for three fluorescent bead species and good a separation for a four-colour fixed-cell sample was achieved. This was done for the first time by purely distinguishing the different emission spectra using only one wavelength for excitation and a single STED beam for depletion

Electoral Volatility, Political Sophistication, Trust and Efficacy

In this article we investigate voter volatility and analyze the causes and motives of switching vote intentions. We test two main sets of variables linked to volatility in literature; political sophistication and ‘political (dis)satisfaction’. Results show that voters with low levels of political efficacy tend to switch more often, both within a campaign and between elections. In the analysis we differentiate between campaign volatility and inter-election volatility and by doing so show that the dynamics of a campaign have a profound impact on volatility. The campaign period is when the lowly sophisticated switch their vote intention. Those with higher levels of interest in politics have switched their intention before the campaign has started. The data for this analysis are from the three wave PartiRep Belgian Election Study (2009)

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.Fil: Quintá, Héctor Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentin