Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

Nonstationary Stochastic Resonance in a Single Neuron-Like System

Stochastic resonance holds much promise for the detection of weak signals in the presence of relatively loud noise. Following the discovery of nondynamical and of aperiodic stochastic resonance, it was recently shown that the phenomenon can manifest itself even in the presence of nonstationary signals. This was found in a composite system of differentiated trigger mechanisms mounted in parallel, which suggests that it could be realized in some elementary neural networks or nonlinear electronic circuits. Here, we find that even an individual trigger system may be able to detect weak nonstationary signals using stochastic resonance. The very simple modification to the trigger mechanism that makes this possible is reminiscent of some aspects of actual neuron physics. Stochastic resonance may thus become relevant to more types of biological or electronic systems injected with an ever broader class of realistic signals.Comment: Plain Latex, 7 figure

Stochastic Resonance in Ion Channels Characterized by Information Theory

We identify a unifying measure for stochastic resonance (SR) in voltage dependent ion channels which comprises periodic (conventional), aperiodic and nonstationary SR. Within a simplest setting, the gating dynamics is governed by two-state conductance fluctuations, which switch at random time points between two values. The corresponding continuous time point process is analyzed by virtue of information theory. In pursuing this goal we evaluate for our dynamics the tau-information, the mutual information and the rate of information gain. As a main result we find an analytical formula for the rate of information gain that solely involves the probability of the two channel states and their noise averaged rates. For small voltage signals it simplifies to a handy expression. Our findings are applied to study SR in a potassium channel. We find that SR occurs only when the closed state is predominantly dwelled. Upon increasing the probability for the open channel state the application of an extra dose of noise monotonically deteriorates the rate of information gain, i.e., no SR behavior occurs.Comment: 10 pages, 2 figures, to appear in Phys. Rev.

The stable oxygen isotope ratio of resin extractable phosphate derived from fresh cattle faeces

Phosphorus losses from agriculture pose an environmental threat to watercourses. A new approach using the stable oxygen isotope ratio of oxygen in phosphate (δ18OPO4 value) may help elucidate some phosphorus sources and cycling. Accurately determined and isotopically distinct source values are essential for this process. The δ18OPO4 values of animal wastes have, up to now, received little attention. Methods Phosphate (PO4) was extracted from cattle faeces using anion resins and the contribution of microbial PO4 was assessed. The δ18OPO4 value of the extracted PO4 was measured by precipitating silver phosphate and subsequent analysis on a thermal conversion elemental analyser at 1400°C, with the resultant carbon monoxide being mixed with a helium carrier gas passed through a GC column into a mass spectrometer. Faecal water oxygen isotope ratios (δ18OH2O values) were determined on a dual-inlet mass spectrometer through a process of headspace carbon dioxide equilibration with water samples. Results Microbiological results indicated that much of extracted PO4 was not derived directly from the gut fauna lysed during the extraction of PO4 from the faeces. Assuming that the faecal δ18OH2O values represented cattle body water, the predicted pyrophosphatase equilibrium δ18OPO4 (Eδ18OPO4) values ranged between +17.9 and +19.9‰, while using groundwater δ18OH2O values gave a range of +13.1 to +14.0‰. The faecal δ18OPO4 values ranged between +13.2 and +15.3‰. Conclusions The fresh faecal δ18OPO4 values were equivalent to those reported elsewhere for agricultural animal slurry. However, they were different from the Eδ18OPO4 value calculated from the faecal δ18OH2O value. Our results indicate that slurry PO4 is, in the main, derived from animal faeces although an explanation for the observed value range could not be determined

Nonstationary Stochastic Resonance

It is by now established that, remarkably, the addition of noise to a nonlinear system may sometimes facilitate, rather than hamper the detection of weak signals. This phenomenon, usually referred to as stochastic resonance, was originally associated with strictly periodic signals, but it was eventually shown to occur for stationary aperiodic signals as well. However, in several situations of practical interest, the signal can be markedly nonstationary. We demonstrate that the phenomenon of stochastic resonance extends to nonstationary signals as well, and thus could be relevant to a wider class of biological and electronic applications. Building on both nondynamic and aperiodic stochastic resonance, our scheme is based on a multilevel trigger mechanism, which could be realized as a parallel network of differentiated threshold sensors. We find that optimal detection is reached for a number of thresholds of order ten, and that little is gained by going much beyond that number. We raise the question of whether this is related to the fact that evolution has favored some fixed numbers of precisely this order of magnitude in certain aspects of sensory perception.Comment: Plain Latex, 6 figure

The Similarity Hypothesis in General Relativity

Self-similar models are important in general relativity and other fundamental theories. In this paper we shall discuss the ``similarity hypothesis'', which asserts that under a variety of physical circumstances solutions of these theories will naturally evolve to a self-similar form. We will find there is good evidence for this in the context of both spatially homogenous and inhomogeneous cosmological models, although in some cases the self-similar model is only an intermediate attractor. There are also a wide variety of situations, including critical pheneomena, in which spherically symmetric models tend towards self-similarity. However, this does not happen in all cases and it is it is important to understand the prerequisites for the conjecture.Comment: to be submitted to Gen. Rel. Gra

Forward coherent ϕ\phi-meson photoproduction from deuterons near threshold

Differential cross sections and decay asymmetries for coherent $\phi$-meson photoproduction from deuterons were measured for the first time at forward angles using linearly polarized photons at $E_{\gamma}$= 1.5-2.4 GeV. This reaction offers a unique way to directly access natural-parity Pomeron dynamics and gluon exchange at low energies. The cross sections at zero degrees increase with increasing photon energy. The decay asymmetries demonstrate a complete dominance of natural-parity exchange processes, showing that isovector unnatural-parity $\pi$-meson exchange is small. Nevertheless the deduced cross sections of $\phi$-mesons from nucleons contributed by isoscalar t-channel exchange processes are not well described by the conventional Pomeron model.Comment: 14 pages, 6 figures. Final published versio

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio