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

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

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

Galaxies Probing Galaxies at High Resolution: Co-Rotating Gas Associated with a Milky Way Analog at z=0.4

We present results on gas flows in the halo of a Milky Way-like galaxy at z=0.413 based on high-resolution spectroscopy of a background galaxy. This is the first study of circumgalactic gas at high spectral resolution towards an extended background source (i.e., a galaxy rather than a quasar). Using longslit spectroscopy of the foreground galaxy, we observe spatially extended H alpha emission with circular rotation velocity v=270 km/s. Using echelle spectroscopy of the background galaxy, we detect Mg II and Fe II absorption lines at impact parameter rho=27 kpc that are blueshifted from systemic in the sense of the foreground galaxy's rotation. The strongest absorber EW(2796) = 0.90 A has an estimated column density (N_H>10^19 cm-2) and line-of-sight velocity dispersion (sigma=17 km/s) that are consistent with the observed properties of extended H I disks in the local universe. Our analysis of the rotation curve also suggests that this r=30 kpc gaseous disk is warped with respect to the stellar disk. In addition, we detect two weak Mg II absorbers in the halo with small velocity dispersions (sigma<10 km/s). While the exact geometry is unclear, one component is consistent with an extraplanar gas cloud near the disk-halo interface that is co-rotating with the disk, and the other is consistent with a tidal feature similar to the Magellanic Stream. We can place lower limits on the cloud sizes (l>0.4 kpc) for these absorbers given the extended nature of the background source. We discuss the implications of these results for models of the geometry and kinematics of gas in the circumgalactic medium.Comment: 14 pages, 6 figures, submitted to ApJ, comments welcom