D-SERINE CONTRIBUTES TO β-AMYLOID-DEPENDENT PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

International audienceB fEPSP/PFV ra>o 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 WT 5xFAD 5xFAD/SR-/-+ D-s e ri n e + D-s e ri n e + D-s e ri n e Key regulators of the structural and funcFonal brain plasFcity, the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) requires the binding of the co-agonist D-serine to be acFvated. In Alzheimer's disease (AD), soluble oligomers of the beta-amyloid pepFde (Aßo) affect NMDARs possibly through mechanisms involving changes in D-serine levels since Aßo sFmulate in vitro the producFon of the co-agonist. In this study, we asked whether D-serine contributes in vivo to morpho-funcFonal NMDAR-related deregulaFons mediated by Aßo. Behavioral analysis combined to electrophysiological recordings at CA1/CA3 hippocampal synapses have been thus conducted in the 5xFAD transgenic mice model of amyloïdogenesis displaying marked increase in Aßo rates and compared to 5xFAD animals in which the homozygous gene of the serine racemase (SR) that synthesizes D-serine, has been jointly invalidated. Our results therefore show that deleFon of serine racemase prevents memory-related behavioral deficits observed in mice with prominent features of amyloidogenesis as well as impairment of NMDAR-dependent funcFonal plasFcity, suggesFng a significant contribuFon of D-serine in NMDAR-dependent β-amyloid-related pathophysiology of Alzheimer's disease. EXPERIMENTAL PROCEDURES 1) Behavioral analysis: 8-min spontaneous alternaFon test was performed in a Y maze apparatus to assess working memory performances in 10-12 months of aged mice. Successive entry of the three arms of the maze was considered as an alternaFon. The percentage of alternaFon was calculated as follows: number of alternaFons / (total number of arms visited-2) x 100. 2) Electrophysiology: Hippocampal slices (400 µm thickness) were cut from two groups of WT, 5xFAD/SR +/+ and 5xFAD/SR-/-mice aged 3-4 or 10-12 months. Field excitatory postsynapFc potenFals (fEPSPs) and presynapFc fiber volley (PFV) were extracellularly recorded in CA1 stratum radiatum aner electrical sFmulaFon of Schaffer collaterals. Input/output curves of the fEPSP/PFV raFo of isolated NMDAr-mediated fEPSPs were constructed in a low magnesium medium supplemented with the non-NMDAr antagonist NBQX (10µM) before and 15 min aner addiFon of D-serine (100 µM). High frequency (HFS)-induced long-term potenFaFon (LTP) was studied in control medium aner tetanic sFmulaFon consisFng in one train at 100 Hz delivered for 1 sec. TesFng sFmulaFon was then resumed for 60 min aner HFS. 3) Semi-quanFtaFve immunoblopng analysis: Hippocampal Fssue was homogenized in protein lysis buffer. The membranes were probed with anFbodiesaginst GluN1 (1:750

Micromegas detector developments for MIMAC

The aim of the MIMAC project is to detect non-baryonic Dark Matter with a directional TPC. The recent Micromegas efforts towards building a large size detector will be described, in particular the characterization measurements of a prototype detector of 10 $\times$ 10 cm$^2$ with a 2 dimensional readout plane. Track reconstruction with alpha particles will be shown.Comment: 8 pages, 7 figures Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 2011; corrections on author affiliation

Low energy electron/recoil discrimination for directional Dark Matter detection

Directional detection is a promising Dark Matter search strategy. Even though it could accommodate to a sizeable background contamination, electron/recoil discrimination remains a key and challenging issue as for direction-insensitive detectors. The measurement of the 3D track may be used to discriminate electrons from nuclear recoils. While a high rejection power is expected above 20 keV ionization, a dedicated data analysis is needed at low energy. After identifying discriminant observables, a multivariate analysis, namely a Boosted Decision Tree, is proposed, enabling an efficient event tagging for Dark Matter search. We show that it allows us to optimize rejection while keeping a rather high efficiency which is compulsory for rare event search.With respect to a sequential analysis, the rejection is about 20 times higher with a multivariate analysis, for the same Dark Matter exclusion limit.Comment: 20 pages, 20 figure

Probing neutralino dark matter in the MSSM & the NMSSM with directional detection

We investigate the capability of directional detectors to probe neutralino dark matter in the Minimal Supersymmetric Standard Model and the Next-to-Minimal Supersymmetric Standard Model with parameters defined at the weak scale. We show that directional detectors such as the future MIMAC detector will probe spin dependent dark matter scattering on nucleons that are beyond the reach of current spin independent detectors. The complementarity between indirect searches, in particular using gamma rays from dwarf spheroidal galaxies, spin dependent and spin independent direct search techniques is emphasized. We comment on the impact of the negative results on squark searches at the LHC. Finally, we investigate how the fundamental parameters of the models can be constrained in the event of a dark matter signal.Comment: 21 pages, 16 figure

D-­‐SERINE IS INVOLVED IN THE β-­‐AMYLOID-­‐RELATED PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

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Quenching factor measurement in low pressure gas detector for directional dark matter search

There is considerable experimental effort dedicated to the directional detection of particle dark matter. Gaseous mu-TPC detectors present the privileged features of being able to reconstruct the track and the energy of the recoil nucleus following the interaction. A precise measurement of the recoil energy is a key point for the directional search strategy. Quenching has to be taken into account, i.e. only a certain fraction of the recoil energy is deposited in the ionization channel. Measurements of the ionization quenching factor for different gas mixture at room temperature have been made with a dedicated ion beam facility at the LPSC of Grenoble.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

A fourfold coordinated point defect in silicon

Due to their technological importance, point defects in silicon are among the best studied physical systems. The experimental examination of point defects buried in bulk is difficult and evidence for the various defects usually indirect. Simulations of defects in silicon have been performed at various levels of sophistication ranging from fast force fields to accurate density functional calculations. The generally accepted viewpoint from all these studies is that vacancies and self interstitials are the basic point defects in silicon. We challenge this point of view by presenting density functional calculations that show that there is a new fourfold coordinated point defect in silicon that is lower in energy

Social presence and dishonesty in retail

Self-service checkouts (SCOs) in retail can benefit consumers and retailers, providing control and autonomy to shoppers independent from staff, together with reduced queuing times. Recent research indicates that the absence of staff may provide the opportunity for consumers to behave dishonestly, consistent with a perceived lack of social presence. This study examined whether a social presence in the form of various instantiations of embodied, visual, humanlike SCO interface agents had an effect on opportunistic behaviour. Using a simulated SCO scenario, participants experienced various dilemmas in which they could financially benefit themselves undeservedly. We hypothesised that a humanlike social presence integrated within the checkout screen would receive more attention and result in fewer instances of dishonesty compared to a less humanlike agent. This was partially supported by the results. The findings contribute to the theoretical framework in social presence research. We concluded that companies adopting self-service technology may consider the implementation of social presence in technology applications to support ethical consumer behaviour, but that more research is required to explore the mixed findings in the current study.<br/

CDMSlite: A Search for Low-Mass WIMPs using Voltage-Assisted Calorimetric Ionization Detection in the SuperCDMS Experiment

SuperCDMS is an experiment designed to directly detect Weakly Interacting Massive Particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this paper, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage- assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for 10 live days at the Soudan Underground Laboratory. A low energy threshold of 170 eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6 GeV/c2.Comment: 7 pages, 4 figure