SYNAPTIC AVAILABILITY OF GLUN2A SUBUNIT OF NMDA RECEPTORS FROM PHYSIOLOGICAL MECHANISMS TO 
PATHOLOGY: THE ROLE OF RABPHILIN 3A

Background and Purpose - NMDA receptor subunit composition strictly commands receptor function and pharmacological responses. The identity of the GluN2 subunit regulates biophysical and pharmacological properties of the receptor and influences receptor assembly, signaling and trafficking to the postsynaptic membrane. The number or subunit composition of NMDA receptors vary during activity dependent plasticity and CNS disorders like Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) where you can find an enhanced extrasynaptic localization of GluN2B-containing NMDA receptors and an increase of the GluN2A/GluN2B ratio at striatal synapses. Recently, a two-hybrid screening to find potential proteins interacting with the C-terminal tail of the GluN2A subunit of the NMDA receptor has highlighted Rabphilin 3A (Rph3A) as a potential partner. Rph3A is a synaptic vesicle-associated protein that was first identified as a binding partner of the GTP-bound Rab3A, a member of the Rab family of GTPases implicated in vesicle docking/fusion reactions. Moreover, different studies have indicated that Rph3A can regulate exo- and endocytosis processes at synaptic sites. Our goal was to characterize Rph3A interaction with GluN2A at postynaptic sites and to assess its relevance in PD and LID. Methods and Results - Firstly, we verified its interaction with GluN2A by immunoprecipitation and GST pull-down experiments. Subcellular fractionation assays revealed that Rph3A is present in Triton Insoluble Postsynaptic compartment and post-synaptic density (PSD) fractions. Immunofluorescence studies performed in neuronal hippocampal cultures, confirmed biochemical experiments revealing Rph3A colocalization with PSD-95 (marker of the postsynaptic compartment) and GluN2A. Moreover, we found Rph3A to be interacting with a 40AA domain on C-terminal tail of GluN2A between AA 1349 and 1389. Therefore, we designed a cell permeable peptide containing this sequence called TAT-2A-40. This peptide is capable of disrupting the interaction between Rph3A and GluN2A. By doing this, it can reduce the expression of GluN2A in dendritic spines and its surface expression as we show by immunocytochemistry and electrophysiology. Moreover, we have observed an increase of GluN2A/Rph3A interaction in a rat PD model as well as a rat LID model. We have that the TAT-2A-40 was capable of significantly reducing the dyskinetic behavior in these animals. Conclusions - These results strongly indicate the presence of Rph3A in the PSD compartment and suggest a function of Rph3A in the modulation of NR2A localization. Rph3A could play a crucial role in the stabilization of GluN2A subunits at the plasma membrane in dendritic spines. Therefore, this interaction could be a potential therapeutic target for diseases where NMDAR composition is significantly altered such as Parkinson's Disease and L-DOPA-induced dyskinesia

Dissipative Quantum Ising model in a cold atomic spin-boson mixture

Using cold bosonic atoms with two (hyperfine) ground states, we introduce a spin-boson mixture which allows to implement the quantum Ising model in a tunable dissipative environment. The first specie lies in a deep optical lattice with tightly confining wells and forms a spin array; spin-up/down corresponds to occupation by one/no atom at each site. The second specie forms a superfluid reservoir. Different species are coupled coherently via laser transitions and collisions. Whereas the laser coupling mimics a transverse field for the spins, the coupling to the reservoir sound modes induces a ferromagnetic (Ising) coupling as well as dissipation. This gives rise to an order-disorder quantum phase transition where the effect of dissipation can be studied in a controllable manner.Comment: 4 pages, 2 figures, 1 table; Title modified and cosmetic change

PRIMUS: An observationally motivated model to connect the evolution of the AGN and galaxy populations out to z~1

We present an observationally motivated model to connect the AGN and galaxy populations at 0.2<z<1.0 and predict the AGN X-ray luminosity function (XLF). We start with measurements of the stellar mass function of galaxies (from the Prism Multi-object Survey) and populate galaxies with AGNs using models for the probability of a galaxy hosting an AGN as a function of specific accretion rate. Our model is based on measurements indicating that the specific accretion rate distribution is a universal function across a wide range of host stellar mass with slope gamma_1 = -0.65 and an overall normalization that evolves with redshift. We test several simple assumptions to extend this model to high specific accretion rates (beyond the measurements) and compare the predictions for the XLF with the observed data. We find good agreement with a model that allows for a break in the specific accretion rate distribution at a point corresponding to the Eddington limit, a steep power-law tail to super-Eddington ratios with slope gamma_2 = -2.1 +0.3 -0.5, and a scatter of 0.38 dex in the scaling between black hole and host stellar mass. Our results show that samples of low luminosity AGNs are dominated by moderately massive galaxies (M* ~ 10^{10-11} M_sun) growing with a wide range of accretion rates due to the shape of the galaxy stellar mass function rather than a preference for AGN activity at a particular stellar mass. Luminous AGNs may be a severely skewed population with elevated black hole masses relative to their host galaxies and in rare phases of rapid accretion.Comment: 11 pages, 5 figures, emulateapj format, updated to match version accepted for publication in Ap

Geant4 Simulation of a filtered X-ray Source for Radiation Damage Studies

Geant4 low energy extensions have been used to simulate the X-ray spectra of industrial X-ray tubes with filters for removing the uncertain low energy part of the spectrum in a controlled way. The results are compared with precisely measured X-ray spectra using a silicon drift detector. Furthermore, this paper shows how the different dose rates in silicon and silicon dioxide layers of an electronic device can be deduced from the simulations

PRIMUS + DEEP2: Clustering of X-ray, Radio and IR-AGN at z~0.7

We measure the clustering of X-ray, radio, and mid-IR-selected active galactic nuclei (AGN) at 0.2 < z < 1.2 using multi-wavelength imaging and spectroscopic redshifts from the PRIMUS and DEEP2 redshift surveys, covering 7 separate fields spanning ~10 square degrees. Using the cross-correlation of AGN with dense galaxy samples, we measure the clustering scale length and slope, as well as the bias, of AGN selected at different wavelengths. Similar to previous studies, we find that X-ray and radio AGN are more clustered than mid-IR-selected AGN. We further compare the clustering of each AGN sample with matched galaxy samples designed to have the same stellar mass, star formation rate, and redshift distributions as the AGN host galaxies and find no significant differences between their clustering properties. The observed differences in the clustering of AGN selected at different wavelengths can therefore be explained by the clustering differences of their host populations, which have different distributions in both stellar mass and star formation rate. Selection biases inherent in AGN selection, therefore, determine the clustering of observed AGN samples. We further find no significant difference between the clustering of obscured and unobscured AGN, using IRAC or WISE colors or X-ray hardness ratio.Comment: Accepted to ApJ. 23 emulateapj pages, 15 figures, 4 table

The Line Emission Region in III Zw 2: Kinematics and Variability

We have studied the Ly-al, Hbeta, Halpha and Mg II2798 line profiles of the Seyfert 1 galaxy III Zw 2. The shapes of these broad emission lines show evidence of a multicomponent origin and also features which may be identified as the peaks due to a rotating disk. We have proposed a two-component Broad Line Region (BLR) model consisting of an inner Keplerian relativistic disk and an outer structure surrounding the disk. The results of the fitting of the four Broad Emission Lines (BELs) here considered, are highly consistent in both the inner and outer component parameters. Adopting a mass of approx. 2 E8 sollar masses for the central object we found that the outer radius of the disk is approximately equal for the four considered lines (approx 0.01 pc). However, the inner radius of the disk is not the same: 0.0018 pc for Ly-alpha, 0.0027 pc for Mg II, and 0.0038 pc for the Balmer lines. This as well as the relatively broad component present in the blue wings of the narrow [OIII] lines indicate stratification in the emission-line region. Using long-term Hbeta observations (1972-1990, 1998) we found a flux variation of the BEL with respect to the [OIII] lines.Comment: ApJ, accepted, 22 pages, 10 figure

SDSS IV MaNGA - Rotation Velocity Lags in the Extraplanar Ionized Gas from MaNGA Observations of Edge-on Galaxies

We present a study of the kinematics of the extraplanar ionized gas around several dozen galaxies observed by the Mapping of Nearby Galaxies at the Apache Point Observatory (MaNGA) survey. We considered a sample of 67 edge-on galaxies out of more than 1400 extragalactic targets observed by MaNGA, in which we found 25 galaxies (or 37%) with regular lagging of the rotation curve at large distances from the galactic midplane. We model the observed $H\alpha$ emission velocity fields in the galaxies, taking projection effects and a simple model for the dust extinction into the account. We show that the vertical lag of the rotation curve is necessary in the modeling, and estimate the lag amplitude in the galaxies. We find no correlation between the lag and the star formation rate in the galaxies. At the same time, we report a correlation between the lag and the galactic stellar mass, central stellar velocity dispersion, and axial ratio of the light distribution. These correlations suggest a possible higher ratio of infalling-to-local gas in early-type disk galaxies or a connection between lags and the possible presence of hot gaseous halos, which may be more prevalent in more massive galaxies. These results again demonstrate that observations of extraplanar gas can serve as a potential probe for accretion of gas.Comment: 13 pages, 11 figures, accepted for publication in Ap