N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake.

BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks. RESULTS: NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats. CONCLUSIONS: Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.This research was supported by a French Institute of Health and Medical Research Avenir and an ANR12 SAMA00201 Grant (to DB) as well as a Newton Trust/Cambridge University Grant (to DB). BJE and JEM are supported by a Medical Research Council (G9536855, G0701500) Grant to BJE and by a joint award from the Medical Research Council and Wellcome Trust in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University

Production of medium-mass neutron-rich nuclei in reactions induced by 136Xe projectiles at 1 A GeV on a beryllium target

Production cross sections of medium-mass neutron-rich nuclei obtained in the fragmentation of 136Xe projectiles at 1 A GeV have been measured with the FRagment Separator (FRS) at GSI. 125Pd was identified for the first time. The measured cross sections are compared to 238U fission yields and model calculations in order to determine the optimum reaction mechanism to extend the limits of the chart of the nuclides around the r-process waiting point at N=82.Comment: 9 pages, 6 figure

Quaiselastic scattering from relativistic bound nucleons: Transverse-Longitudinal response

Predictions for electron induced proton knockout from the $p_{1/2}$ and $p_{3/2}$ shells in $^{16}$O are presented using various approximations for the relativistic nucleonic current. Results for the differential cross section, transverse-longitudinal response ($R_{TL}$) and left-right asymmetry $A_{TL}$ are compared at $|Q^2|=0.8$ (GeV/c)$^2$ corresponding to TJNAF experiment 89-003. We show that there are important dynamical and kinematical relativistic effects which can be tested by experiment.Comment: 10 pages, including 2 figures. Removed preliminary experimental data from the figure

Coincidence measurement of residues and light particles in the reaction 56Fe+p at 1 GeV per nucleon with SPALADIN

The spallation of $^{56}$Fe in collisions with hydrogen at 1 A GeV has been studied in inverse kinematics with the large-aperture setup SPALADIN at GSI. Coincidences of residues with low-center-of-mass kinetic energy light particles and fragments have been measured allowing the decomposition of the total reaction cross-section into the different possible de-excitation channels. Detailed information on the evolution of these de-excitation channels with excitation energy has also been obtained. The comparison of the data with predictions of several de-excitation models coupled to the INCL4 intra-nuclear cascade model shows that only GEMINI can reasonably account for the bulk of collected results, indicating that in a light system with no compression and little angular momentum, multifragmentation might not be necessary to explain the data.Comment: 4 pages, 5 figures, revised version accepted in Phys. Rev. Let

Atmospheric drying as the main driver of dramatic glacier wastage in the southern Indian Ocean

This study was funded by IPEV-1048 GLACIOCLIM-KESAACO and LEFE-INSU KCRuMBLE programs, and the Agence Nationale de la Recherche through contract ANR-14-CE01-0001-01 (ASUMA).The ongoing retreat of glaciers at southern sub-polar latitudes is particularly rapid and widespread. Akin to northern sub-polar latitudes, this retreat is generally assumed to be linked to warming. However, no long-term and well-constrained glacier modeling has ever been performed to confirm this hypothesis. Here, we model the Cook Ice Cap mass balance on the Kerguelen Islands (Southern Indian Ocean, 49°S) since the 1850s. We show that glacier wastage during the 2000s in the Kerguelen was among the most dramatic on Earth. We attribute 77% of the increasingly negative mass balance since the 1960s to atmospheric drying associated with a poleward shift of the mid-latitude storm track. Because precipitation modeling is very challenging for the current generation of climate models over the study area, models incorrectly simulate the climate drivers behind the recent glacier wastage in the Kerguelen. This suggests that future glacier wastage projections should be considered cautiously where changes in atmospheric circulation are expected.Publisher PDFPeer reviewe

Measurement of residual nucleus cross sections and recoil energies in p + Fe collisions at 300, 500, 750, 1000 and 1500 MeV

The production of residual nuclei in p + Fe collisions has been measured at GSI on the FRS facility by means of the reverse kinematic techniques at 300, 500, 750, 1000 and 1500 MeV/A. The cross-sections larger than 0.01 mb of all isotopes with Z larger than 8 have been obtained. Velocity distributions were also measured. Comparisons to models describing spallation reactions and some empirical formulae often used in astrophysics are presented. These data are directly used to calculate impurety production and DPAs in a thin window as foreseen in spallation sources or accelerator-driven systems

Phenomenology of the Deuteron Electromagnetic Form Factors

A rigorous extraction of the deuteron charge form factors from tensor polarization data in elastic electron-deuteron scattering, at given values of the 4-momentum transfer, is presented. Then the world data for elastic electron-deuteron scattering is used to parameterize, in three different ways, the three electromagnetic form factors of the deuteron in the 4-momentum transfer range 0-7 fm^-1. This procedure is made possible with the advent of recent polarization measurements. The parameterizations allow a phenomenological characterization of the deuteron electromagnetic structure. They can be used to remove ambiguities in the form factors extraction from future polarization data.Comment: 18 pages (LaTeX), 2 figures Feb. 25: minor changes of content and in Table

The function of CozE proteins is linked to lipoteichoic acid biosynthesis in Staphylococcus aureus.

Coordinated membrane and cell wall synthesis is vital for maintaining cell integrity and facilitating cell division in bacteria. However, the molecular mechanisms that underpin such coordination are poorly understood. Here we uncover the pivotal roles of the staphylococcal proteins CozEa and CozEb, members of a conserved family of membrane proteins previously implicated in bacterial cell division, in the biosynthesis of lipoteichoic acids (LTA) and maintenance of membrane homeostasis in Staphylococcus aureus. We establish that there is a synthetic lethal relationship between CozE and UgtP, the enzyme synthesizing the LTA glycolipid anchor Glc <sub>2</sub> DAG. By contrast, in cells lacking LtaA, the flippase of Glc <sub>2</sub> DAG, the essentiality of CozE proteins was alleviated, suggesting that the function of CozE proteins is linked to the synthesis and flipping of the glycolipid anchor. CozE proteins were indeed found to modulate the flipping activity of LtaA in vitro. Furthermore, CozEb was shown to control LTA polymer length and stability. Together, these findings establish CozE proteins as novel players in membrane homeostasis and LTA biosynthesis in S. aureus.IMPORTANCELipoteichoic acids are major constituents of the cell wall of Gram-positive bacteria. These anionic polymers are important virulence factors and modulators of antibiotic susceptibility in the important pathogen Staphylococcus aureus. They are also critical for maintaining cell integrity and facilitating proper cell division. In this work, we discover that a family of membrane proteins named CozE is involved in the biosynthesis of lipoteichoic acids (LTAs) in S. aureus. CozE proteins have previously been shown to affect bacterial cell division, but we here show that these proteins affect LTA length and stability, as well as the flipping of glycolipids between membrane leaflets. This new mechanism of LTA control may thus have implications for the virulence and antibiotic susceptibility of S. aureus