PSD95 and nNOS interaction as a novel molecular target to modulate conditioned fear: relevance to PTSD

Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists and NOS inhibitors can disrupt fear conditioning, but they also affect many other CNS functions such as motor activity, anxiety, and learning. We hypothesized that disrupting nNOS and PSD95 interaction in the amygdala, a critical site for fear memory formation, will reduce conditioned fear. Our results show that systemic treatment with ZL006, a compound that disrupts PSD95/nNOS binding, attenuates fear memory compared to its inactive isomer ZL007. Co-immunoprecipitation after fear conditioning showed a robust increase in the amygdala PSD95/nNOS binding, which was blocked by systemic pre-administration of ZL006. Treatment of amygdala slices with ZL006 also impaired long-term potentiation (LTP), a cellular signature of synaptic plasticity. Direct intra-amygdala infusion of ZL006 also attenuated conditioned fear. Finally, unlike NMDAR antagonist MK-801, ZL006 does not affect locomotion, social interaction, object recognition memory, and spatial memory. These findings support the hypothesis that disrupting the PSD95/nNOS interaction downstream of NMDARs selectively reduces fear memory, and highlights PSD95/nNOS interaction as a novel target for fear-related disorders, such as posttraumatic stress disorder

PAMELA Observation of the 2012 May 17 GLE Event

The PAMELA (Payload for Antimatter Matter Exploration and Light-nuclei Astrophysics) satellite-borne experiment has been collecting data in orbit since July 2006, providing accurate measurements of the energy spectra and composition of the cosmic radiation from a few hundred MeVn up to hundred GeVn. This wide interval of measured energies makes PAMELA a unique instrument for Solar Energetic Particle (SEP) observations. Not only does it span the energy range between the ground-based neutron monitor data and the observations of SEPs from space, but also PAMELA carries out the first direct measurements of the composition for the highest energy SEP events, including those causing Ground Level Enhancements (GLEs). PAMELA has registered many SEP events in solar cycle 24 including the 2012 May 17 GLE event (GLE 71), offering unique opportunities to address the question of high-energy SEP origin. Experimental performances and preliminary results on the 2012 May 17 events will be presented. We will discuss the derived particle injection time and compare with other time scales at the Sun including the flare and CME onset times

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe

ϒ production in p–Pb collisions at √sNN=8.16 TeV

ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

(Anti-)deuteron production in pp collisions at 1as=13TeV

The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)