Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

The dependence of the anomalous J/psi suppression on the number of participant nucleons

The observation of an anomalous J/psi suppression in Pb-Pb collisions by the NA50 Collaboration can be considered as the most striking indication for the deconfinement of quarks and gluons at SPS energies. In this Letter, we determine the J/psi suppression pattern as a function of the forward hadronic energy E-ZDC measured in a Zero Degree Calorimeter (ZDC). The direct connection between EZDC and the geometry of the collision allows us to calculate, within a Glauber approach, the precise relation between the number of participant nucleons N-part and E-ZDC. Then, we check if the experimental data can be better explained by a sudden or a smooth onset of the anomalous J/psi suppression as a function of the number of participants. (C) 2001 Elsevier Science B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

Centrality Behaviour of J/ψ\psi Production in Na50

The J/$\psi$ production in 158 A GeV Pb-Pb interactions is studied, in the dimuon decay channel, as a function of centrality, as measured with the electromagnetic or with the very forward calorimeters. After a first sharp variation at mid centrality, both patterns continue to fall down and exhibit a curvature change at high centrality values. This trend excludes any conventional hadronic model and is in agreement with a deconfined quark-gluon phase scenario. We report also preliminary results on the measured charged multiplicity, as given by a dedicated detector.Comment: 5 pages, 7 figures (in eps) talk given at XXXI International Symposium on Multiparticle Dynamics, Sep. 1-7, 2001, Datong China URL http://ismd31.ccnu.edu.cn

Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer\u27s Disease Progression

Alzheimer\u27s disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing partial RNA dependency. Comparisons of brain tissue and cerebrospinal fluid proteomes reveal biomarker candidates. Combining with 5xFAD mouse analysis, we determine 15 Aβ-correlated proteins (e.g., MDK, NTN1, SMOC1, SLIT2, and HTRA1). 5xFAD shows a proteomic signature similar to symptomatic AD but exhibits activation of autophagy and interferon response and lacks human-specific deleterious events, such as downregulation of neurotrophic factors and synaptic proteins. Multi-omics integration prioritizes AD-related molecules and pathways, including amyloid cascade, inflammation, complement, WNT signaling, TGF-β and BMP signaling, lipid metabolism, iron homeostasis, and membrane transport. Some Aβ-correlated proteins are colocalized with amyloid plaques. Thus, the multilayer omics approach identifies protein networks during AD progression

Charmonia production in 450 GeV/c proton-induced reactions

Absolute \jpsi\ and \psip\ production cross sections have been measured at the CERN SPS, with 450~GeV/$c$ protons incident on a set of C, Al, Cu and W targets. Complementing these values with the results obtained by experiment NA51, which used the same beam and detector with H and D targets, we establish a coherent picture of charmonia production in proton-induced reactions at SPS energies. In particular, we show that the scaling of the \jpsi\ cross section with the mass number of the target, A, is well described as A$^\alpha$ with $\alpha^\psi=0.919\pm0.015$. The ratio between the \jpsi\ and \psip\ yields, in our kinematical window, is found to be independent of A, with $\alpha^{\psi^\prime}-\alpha^{\psi}=0.014\pm0.0 11$

CMS Forward-Backward MSGC milestone

The CMS MF1 milestone was set in order to evaluate system aspects of the CMS forward-backward MSGC tracker, to check the design and feasibility of mass production and to set up assembly and test procedures. We describe the construction and the experience gained with the operation of a system of 38 MSGC detectors assembled in six multi-substrate detector modules corresponding to the geometry of the forward-backward MSGC tracker in CMS. These modules were equipped with MSGCs mounted side by side, forming a continuous detector surface of about 0.2 m2. Different designs were tried for these modules. The problems encountered are presented with the proposed solutions. Operation conditions for the 38 MSGCs are reported from an exposure to a muon beam at the CERN SPS. Gain uniformity along the wedge-shaped strip pattern and across the detector modules are shown together with the detection efficiency, the spatial resolution, alignment and edge studies