Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene

Dynamic changes in synaptic connectivity and strength, which occur during both embryonic development and learning, have the tendency to destabilize neural circuits. To overcome this, neurons have developed a diversity of homeostatic mechanisms to maintain firing within physiologically defined limits. In this study, we show that activity-dependent control of mRNA for a specific voltage-gated Na+ channel [encoded by paralytic (para)] contributes to the regulation of membrane excitability in Drosophila motoneurons. Quantification of para mRNA, by real-time reverse-transcription PCR, shows that levels are significantly decreased in CNSs in which synaptic excitation is elevated, whereas, conversely, they are significantly increased when synaptic vesicle release is blocked. Quantification of mRNA encoding the translational repressor pumilio (pum) reveals a reciprocal regulation to that seen for para. Pumilio is sufficient to influence para mRNA. Thus, para mRNA is significantly elevated in a loss-of-function allele of pum (pumbemused), whereas expression of a full-length pum transgene is sufficient to reduce para mRNA. In the absence of pum, increased synaptic excitation fails to reduce para mRNA, showing that Pum is also necessary for activity-dependent regulation of para mRNA. Analysis of voltage-gated Na+ current (INa) mediated by para in two identified motoneurons (termed aCC and RP2) reveals that removal of pum is sufficient to increase one of two separable INa components (persistent INa), whereas overexpression of a pum transgene is sufficient to suppress both components (transient and persistent). We show, through use of anemone toxin (ATX II), that alteration in persistent INa is sufficient to regulate membrane excitability in these two motoneurons

Patterns of decadal climate variability and their impact on global rainfall

AbstractAn analysis is made of global sea surface temperature (SST) data sets over the past 110 years to determine the principal patterns of climate variability on time scales longer than ENSO, and to relate these to likely dynamical processes. Taking 5-year running means, the most recent versions of the interpolated global data from the UK Hadley Centre and the US NOAA are analysed using singular value decomposition, and described as coherent global patterns that have a physical/dynamical basis. These patterns are: Global Warming, the Pacific Decadal Oscillation, the Atlantic Multi-decadal Oscillation and the Pacific Gyre Oscillation. Each of these patterns, as represented by SST, is described in both data sets with real and complex empirical orthogonal functions, and current understanding of their dynamical basis is described. An example of the use of such patterns is given through an application to the recent trend pattern in global rainfall. Complete agreement between the two SST data sets is lacking, but both agree that major contributors to this rainfall pattern are global warming and the Pacific Decadal Oscillation, where the latter may be regarded as the low-frequency signal of ENSO

Hydraulic flow through a channel contraction: multiple steady states

We have investigated shallow water flows through a channel with a contraction by experimental and theoretical means. The horizontal channel consists of a sluice gate and an upstream channel of constant width $b_0$ ending in a linear contraction of minimum width $b_c$. Experimentally, we observe upstream steady and moving bores/shocks, and oblique waves in the contraction, as single and multiple steady states, as well as a steady reservoir with a complex hydraulic jump in the contraction occurring in a small section of the $b_c/b_0$ and Froude number parameter plane. One-dimensional hydraulic theory provides a comprehensive leading-order approximation, in which a turbulent frictional parametrization is used to achieve quantitative agreement. An analytical and numerical analysis is given for two-dimensional supercritical shallow water flows. It shows that the one-dimensional hydraulic analysis for inviscid flows away from hydraulic jumps holds surprisingly well, even though the two-dimensional oblique hydraulic jump patterns can show large variations across the contraction channel

Servitization transformation:drivers, benefit and barriers

The study described in this paper has set out to build the evidence base underpinning servitization transformation. We applied a Delphi research methodology from 33 senior executives, in 28 different sized organisations, from a cross section of British industry. Our findings focus on servitization: (1) drivers, (2) benefit (3) barriers. The four findings are presented to contribute to our understanding of the transformation processes that manufacturers to compete through servitization

Towards a Framework for Analyzing and Evaluating Servitization Potential: Case Study of ENVIE Loire

Part 4: Transition Towards Product-Service SystemsInternational audienceFor a manufacturing company, moving from selling a product to selling a function is a process called “servitization”, leading to the suggestion of an offer oriented functionality that is more commonly called a Product-Service System (PSS). This process requires for a company to have a relatively clear vision of possible scenarios. Under the ServINNOV project, we proposed after a deep analysis of the main researches on PSS a new approach to analyze the servitization potential. In this paper, we present our conceptual framework for identifying and evaluating the different scenarios and we illustrate the practical use of this approach using the case study of ENVIE Loire which develops remanufacturing activities

Macroscopic and Local Magnetic Moments in Si-doped CuGeO3_3 with Neutron and μ\muSR Studies

The temperature-concentration phase diagram of the Si-doped spin-Peierls compound CuGeO$_{3}$ is investigated by means of neutron scattering and muon spin rotation spectroscopy in order to determine the microscopic distribution of the magnetic and lattice dimerised regions as a function of doping. The analysis of the zero-field muon spectra has confirmed the spatial inhomogeneity of the staggered magnetisation that characterises the antiferromagnetic superlattice peaks observed with neutrons. In addition, the variation of the macroscopic order parameter with doping can be understood by considering the evolution of the local magnetic moment as well as of the various regions contributing to the muon signal

Constrained by managerialism : caring as participation in the voluntary social services

The data in this study show that care is a connective process, underlying and motivating participation and as a force that compels involvement in the lives of others, care is at least a micro-participative process. Care or affinity not only persisted in the face of opposition, but it was also used by workers as a counter discourse and set of practices with which to resist the erosion of worker participation and open up less autonomized practices and ways of connecting with fellow staff, clients and the communities they served. The data suggest that while managerialism and taylorised practice models may remove or reduce opportunities for worker participation, care is a theme or storyline that gave workers other ways to understand their work and why they did it, as well as ways they were prepared to resist managerial priorities and directives, including the erosion of various kinds of direct and indirect participation. The degree of resistance possible, even in the highly technocratic worksite in Australia, shows that cracks and fissures exist within managerialism

Pumilio binds para mRNA and requires nanos and brat to regulate sodium current in drosophila motoneurons

Homeostatic regulation of ionic currents is of paramount importance during periods of synaptic growth or remodeling. Our previous work has identified the translational repressor Pumilio (Pum) as a regulator of sodium current (INa) and excitability in Drosophila motoneurons. In this current study, we show that Pum is able to bind directly the mRNA encoding the Drosophila voltage-gated sodium channel paralytic (para). We identify a putative binding site for Pum in the 3' end of the para open reading frame (ORF). Characterization of the mechanism of action of Pum, using whole-cell patch clamp and real-time reverse transcription-PCR, reveals that the full-length protein is required for translational repression of para mRNA. Additionally, the cofactor Nanos is essential for Pum-dependent para repression, whereas the requirement for Brain Tumor (Brat) is cell type specific. Thus, Pum-dependent regulation of INa in motoneurons requires both Nanos and Brat, whereas regulation in other neuronal types seemingly requires only Nanos but not Brat. We also show that Pum is able to reduce the level of nanos mRNA and as such identify a potential negative-feedback mechanism to protect neurons from overactivity of Pum. Finally, we show coupling between INa (para) and IK (Shal) such that Pum-mediated change in para results in a compensatory change in Shal. The identification of para as a direct target of Pum represents the first ion channel to be translationally regulated by this repressor and the location of the binding motif is the first example in an ORF rather than in the canonical 3'-untranslated region of target transcripts

Using Virtual Observatory techniques to search for Adaptive Optics suitable AGN

Until recently, it has been possible only for nearby galaxies to study the scaling relations between central black hole and host galaxy in detail. Because of the small number densities at low redshift, (luminous) AGN are underrepresented in such detailed studies. The advent of adaptive optics (AO) at large telescopes helps overcoming this hurdle, allowing to reach small linear scales over a wide range in redshift. Finding AO-suitable targets, i.e., AGN having a nearby reference star, and carrying out an initial multiwavelength classification is an excellent use case for the Virtual Observatory. We present our Virtual-Observatory approach to select an AO-suitable catalog of X-ray-emitting AGN at redshifts 0.1<z<1.Comment: 4 pages, 5 figures, submitted to "EURO-VO AIDA workshop: Multiwavelength astronomy and Virtual Observatory", ESAC, Spain, 1-3 Dec. 200