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

A renormalization group invariant scalar glueball operator in the (Refined) Gribov-Zwanziger framework

This paper presents a complete algebraic analysis of the renormalizability of the $d=4$ operator $F^2_{\mu\nu}$ in the Gribov-Zwanziger (GZ) formalism as well as in the Refined Gribov-Zwanziger (RGZ) version. The GZ formalism offers a way to deal with gauge copies in the Landau gauge. We explicitly show that $F^2_{\mu\nu}$ mixes with other $d=4$ gauge variant operators, and we determine the mixing matrix $Z$ to all orders, thereby only using algebraic arguments. The mixing matrix allows us to uncover a renormalization group invariant including the operator $F^2_{\mu\nu}$. With this renormalization group invariant, we have paved the way for the study of the lightest scalar glueball in the GZ formalism. We discuss how the soft breaking of the BRST symmetry of the GZ action can influence the glueball correlation function. We expect non-trivial mass scales, inherent to the GZ approach, to enter the pole structure of this correlation function.Comment: 27 page

A purely algebraic construction of a gauge and renormalization group invariant scalar glueball operator

This paper presents a complete algebraic proof of the renormalizability of the gauge invariant $d=4$ operator $F_{\mu\nu}^2(x)$ to all orders of perturbation theory in pure Yang-Mills gauge theory, whereby working in the Landau gauge. This renormalization is far from being trivial as mixing occurs with other $d=4$ gauge variant operators, which we identify explicitly. We determine the mixing matrix $Z$ to all orders in perturbation theory by using only algebraic arguments and consequently we can uncover a renormalization group invariant by using the anomalous dimension matrix $\Gamma$ derived from $Z$. We also present a future plan for calculating the mass of the lightest scalar glueball with the help of the framework we have set up.Comment: 17 page

Current in the light-front Bethe-Salpeter formalism II: Applications

We pursue applications of the light-front reduction of current matrix elements in the Bethe-Salpeter formalism. The normalization of the reduced wave function is derived from the covariant framework and related to non-valence probabilities using familiar Fock space projection operators. Using a simple model, we obtain expressions for generalized parton distributions that are continuous. The non-vanishing of these distributions at the crossover between kinematic regimes (where the plus component of the struck quark's momentum is equal to the plus component of the momentum transfer) is tied to higher Fock components. Moreover continuity holds due to relations between Fock components at vanishing plus momentum. Lastly we apply the light-front reduction to time-like form factors and derive expressions for the generalized distribution amplitudes in this model.Comment: 12 pages, 6 figures, RevTex

Production and detection of three-qubit entanglement in the Fermi sea

Building on a previous proposal for the entanglement of electron-hole pairs in the Fermi sea, we show how 3 qubits can be entangled without using electron-electron interactions. As in the 2-qubit case, this electronic scheme works even if the sources are in (local) thermal equilibrium -- in contrast to the photonic analogue. The 3 qubits are represented by 4 edge-channel excitations in the quantum Hall effect (2 hole excitations plus 2 electron excitations with identical channel index). The entangler consists of an adiabatic point contact flanked by a pair of tunneling point contacts. The irreducible 3-qubit entanglement is characterized by the tangle, which is expressed in terms of the transmission matrices of the tunneling point contacts. The maximally entangled Greenberger-Horne-Zeilinger (GHZ) state is obtained for channel-independent tunnel probabilities. We show how low-frequency noise measurements can be used to determine an upper and lower bound to the tangle. The bounds become tighter the closer the electron-hole state is to the GHZ state.Comment: 8 pages including 4 figures; [2017: fixed broken postscript figures

Exploring skewed parton distributions with two body models on the light front II: covariant Bethe-Salpeter approach

We explore skewed parton distributions for two-body, light-front wave functions. In order to access all kinematical regimes, we adopt a covariant Bethe-Salpeter approach, which makes use of the underlying equation of motion (here the Weinberg equation) and its Green's function. Such an approach allows for the consistent treatment of the non-wave function vertex (but rules out the case of phenomenological wave functions derived from ad hoc potentials). Our investigation centers around checking internal consistency by demonstrating time-reversal invariance and continuity between valence and non-valence regimes. We derive our expressions by assuming the effective qq potential is independent of the mass squared, and verify the sum rule in a non-relativistic approximation in which the potential is energy independent. We consider bare-coupling as well as interacting skewed parton distributions and develop approximations for the Green's function which preserve the general properties of these distributions. Lastly we apply our approach to time-like form factors and find similar expressions for the related generalized distribution amplitudes.Comment: 25 pages, 12 figures, revised (minor changes but essential to consistency

Generalized Parton Distributions at x->1

Generalized parton distributions at large $x$ are studied in perturbative QCD approach. As $x\to 1$ and at finite $t$, there is no $t$ dependence for the GPDs which means that the active quark is at the center of the transverse space. We also obtain the power behavior: $H_q^\pi(x,\xi,t)\sim (1-x)^2/(1-\xi^2)$ for pion; $H_q(x,\xi,t)\sim (1-x)^3/(1-\xi^2)^2$ and $E_q(x,\xi,t)\sim (1-x)^5/(1-\xi^2)^3f(\xi)$ for nucleon, where $f(\xi)$ represents the additional dependence on $\xi$.Comment: 7 pages, 2 figure

Parton model versus color dipole formulation of the Drell-Yan process

In the kinematical region where the center of mass energy is much larger than all other scales, the Drell-Yan process can be formulated in the target rest frame in terms of the same color dipole cross section as low Bjorken-x deep inelastic scattering. Since the mechanisms for heavy dilepton production appear very different in the dipole approach and in the conventional parton model, one may wonder whether these two formulations really represent the same physics. We perform a comparison of numerical calculations in the color dipole approach with calculations in the next-to-leading order parton model. For proton-proton scattering, the results are very similar at low x_2 from fixed target to RHIC energies, confirming the close connection between these two very different approaches. We also compare the transverse momentum distributions of Drell-Yan dileptons predicted in both formulations. The range of applicability of the dipole formulation and the impact of future Drell-Yan data from RHIC for determining the color dipole cross section are discussed. A detailed derivation of the dipole formulation of the Drell-Yan process is also included.Comment: 20 pages, 5 figure

Emergent global oscillations in heterogeneous excitable media: The example of pancreatic beta cells

Using the standard van der Pol-FitzHugh-Nagumo excitable medium model I demonstrate a novel generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable beta cells, quiescent when isolated, are found to oscillate when coupled despite the absence of a pacemaker region.Comment: See home page http://lec.ugr.es/~julya

Transcriptional and biochemical analyses of gibberellin expression and content in germinated barley grain

Mobilization of reserves in germinated cereal grains is critical for early seedling vigour, global crop productivity and hence food security. Gibberellins (GAs) are central to this process. We have developed a spatio-temporal model that describes the multifaceted mechanisms of GA regulation in germinated barley grain. The model was generated using RNA-seq transcript data from tissues dissected from intact, germinated grain, which closely match measurements of GA hormones and their metabolites in those tissues. The data show that successful grain germination is underpinned by high concentrations of GA precursors in ungerminated grain, the use of independent metabolic pathways for the synthesis of several bioactive GAs during germination, and a capacity to abort bioactive GA biosynthesis. The most abundant bioactive form is GA₁, which is synthesized in the scutellum as a glycosyl conjugate that diffuses to the aleurone, where it stimulates de novo synthesis of a GA₃ conjugate and GA₄. Synthesis of bioactive GAs in the aleurone provides a mechanism that ensures the hormonal signal is relayed from the scutellum to the distal tip of the grain. The transcript dataset of 33,421 genes used to define GA metabolism is available as a resource to analyse other physiological processes in germinated grain.Natalie S. Betts, Christoph Dockter, Oliver Berkowitz, Helen M. Collins, Michelle Hooi, Qiongxian Lu, Rachel A. Burton, Vincent Bulone, Birgitte Skadhauge, James Whelan, and Geoffrey B. Finche