Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism

Collisionless Shock Acceleration of protons in a plasma slab produced in a gas jet by the collision of two laser-driven hydrodynamic shockwaves

We recently proposed a new technique of plasma tailoring by laser-driven hydrodynamic shockwaves generated on both sides of a gas jet [J.-R. Marqu\`es et al., Phys. Plasmas 28, 023103 (2021)]. In the continuation of this numerical work, we studied experimentally the influence of the tailoring on proton acceleration driven by a high-intensity picosecond-laser, in three cases: without tailoring, by tailoring only the entrance side of the ps-laser, or both sides of the gas jet. Without tailoring the acceleration is transverse to the laser axis, with a low-energy exponential spectrum, produced by Coulomb explosion. When the front side of the gas jet is tailored, a forward acceleration appears, that is significantly enhanced when both the front and back sides of the plasma are tailored. This forward acceleration produces higher energy protons, with a peaked spectrum, and is in good agreement with the mechanism of Collisionless Shock Acceleration (CSA). The spatio-temporal evolution of the plasma profile was characterized by optical shadowgraphy of a probe beam. The refraction and absorption of this beam was simulated by post-processing 3D hydrodynamic simulations of the plasma tailoring. Comparison with the experimental results allowed to estimate the thickness and near-critical density of the plasma slab produced by tailoring both sides of the gas jet. These parameters are in good agreement with those required for CSA

Final results of the EDELWEISS-II WIMP search using a 4-kg array of cryogenic germanium detectors with interleaved electrodes

The EDELWEISS-II collaboration has completed a direct search for WIMP dark matter with an array of ten 400-g cryogenic germanium detectors in operation at the Laboratoire Souterrain de Modane. The combined use of thermal phonon sensors and charge collection electrodes with an interleaved geometry enables the efficient rejection of gamma-induced radioactivity as well as near-surface interactions. A total effective exposure of 384 kg.d has been achieved, mostly coming from fourteen months of continuous operation. Five nuclear recoil candidates are observed above 20 keV, while the estimated background is 3.0 events. The result is interpreted in terms of limits on the cross-section of spin-independent interactions of WIMPs and nucleons. A cross-section of 4.4x10^-8 pb is excluded at 90%CL for a WIMP mass of 85 GeV. New constraints are also set on models where the WIMP-nucleon scattering is inelastic.Comment: 23 pages, 5 figures; matches published versio

A search for low-mass WIMPs with EDELWEISS-II heat-and-ionization detectors

We report on a search for low-energy (E < 20 keV) WIMP-induced nuclear recoils using data collected in 2009 - 2010 by EDELWEISS from four germanium detectors equipped with thermal sensors and an electrode design (ID) which allows to efficiently reject several sources of background. The data indicate no evidence for an exponential distribution of low-energy nuclear recoils that could be attributed to WIMP elastic scattering after an exposure of 113 kg.d. For WIMPs of mass 10 GeV, the observation of one event in the WIMP search region results in a 90% CL limit of 1.0x10^-5 pb on the spin-independent WIMP-nucleon scattering cross-section, which constrains the parameter space associated with the findings reported by the CoGeNT, DAMA and CRESST experiments.Comment: PRD rapid communication accepte

Background studies for the EDELWEISS dark matter experiment

The EDELWEISS-II collaboration has completed a direct search for WIMP dark matter using cryogenic Ge detectors (400 g each) and 384 kg$\times$days of effective exposure. A cross-section of $4.4 \times 10^{-8}$ pb is excluded at 90% C.L. for a WIMP mass of 85 GeV. The next phase, EDELWEISS-III, aims to probe spin-independent WIMP-nucleon cross-sections down to a few $\times10^{-9}$ pb. We present here the study of gamma and neutron background coming from radioactive decays in the set-up and shielding materials. We have carried out Monte Carlo simulations for the completed EDELWEISS-II setup with GEANT4 and normalised the expected background rates to the measured radioactivity levels (or their upper limits) of all materials and components. The expected gamma-ray event rate in EDELWEISS-II at 20-200 keV agrees with the observed rate of 82 events/kg/day within the uncertainties in the measured concentrations. The calculated neutron rate from radioactivity of 1.0-3.1 events (90% C.L.) at 20-200 keV in the EDELWEISS-II data together with the expected upper limit on the misidentified gamma-ray events ($\le0.9$), surface betas ($\le0.3$), and muon-induced neutrons ($\le0.7$), do not contradict 5 observed events in nuclear recoil band. We have then extended the simulation framework to the EDELWEISS-III configuration with 800 g crystals, better material purity and additional neutron shielding inside the cryostat. The gamma-ray and neutron backgrounds in 24 kg fiducial mass of EDELWEISS-III have been calculated as 14-44 events/kg/day and 0.7-1.4 events per year, respectively. The results of the background studies performed in the present work have helped to select better purity components and improve shielding in EDELWEISS-III to further reduce the expected rate of background events in the next phase of the experiment.Comment: 15 pages, 9 figures, to be published in Astroparticle Physic

Muon-induced background in the EDELWEISS dark matter search

A dedicated analysis of the muon-induced background in the EDELWEISS dark matter search has been performed on a data set acquired in 2009 and 2010. The total muon flux underground in the Laboratoire Souterrain de Modane (LSM) was measured to be $\Phi_{\mu}=(5.4\pm 0.2 ^{+0.5}_{-0.9})$\,muons/m$^2$/d. The modular design of the muon-veto system allows the reconstruction of the muon trajectory and hence the determination of the angular dependent muon flux in LSM. The results are in good agreement with both MC simulations and earlier measurements. Synchronization of the muon-veto system with the phonon and ionization signals of the Ge detector array allowed identification of muon-induced events. Rates for all muon-induced events $\Gamma^{\mu}=(0.172 \pm 0.012)\, \rm{evts}/(\rm{kg \cdot d})$ and of WIMP-like events $\Gamma^{\mu-n} = 0.008^{+0.005}_{-0.004}\, \rm{evts}/(\rm{kg \cdot d})$ were extracted. After vetoing, the remaining rate of accepted muon-induced neutrons in the EDELWEISS-II dark matter search was determined to be $\Gamma^{\mu-n}_{\rm irred} < 6\cdot 10^{-4} \, \rm{evts}/(\rm{kg \cdot d})$ at 90%\,C.L. Based on these results, the muon-induced background expectation for an anticipated exposure of 3000\,\kgd\ for EDELWEISS-3 is $N^{\mu-n}_{3000 kg\cdot d} < 0.6$ events.Comment: 21 pages, 16 figures, Accepted for publication in Astropart. Phy

A detection system to measure muon-induced neutrons for direct Dark Matter searches

International audienceMuon-induced neutrons constitute a prominent background component in a number of low count rate experiments, namely direct searches for Dark Matter. In this work we describe a neutron detector to measure this background in an underground laboratory, the Laboratoire Souterrain de Modane. The system is based on 1 m of Gd-loaded scintillator and it is linked with the muon veto of the EDELWEISS-II experiment for coincident muon detection. The system was installed in autumn 2008 and passed since then a number of commissioning tests proving its full functionality. The data-taking is continuously ongoing and a count rate of the order of 1 muon-induced neutron per day has been achieved