CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis

BACKGROUND AND AIMS: Fatty acid translocase CD36 (CD36) is a membrane protein with multiple immuno-metabolic functions. Palmitoylation has been suggested to regulate the distribution and functions of CD36, but little is known about its significance in NASH. METHODS: Human liver tissue samples were obtained from patients undergoing liver biopsy for diagnostic purposes. CD36 knockout mice were injected with lentivirus vectors to express wild type CD36 and palmitoylation sites mutated CD36 in the livers. Liver histology, immunofluorescence, mRNA expression profile, subcellular distributions and functions of CD36 protein were assessed. RESULTS: The localization of CD36 on the plasma membrane of hepatocytes was markedly increased in patients with NASH compared to patients with normal liver and those with simple steatosis. Increased CD36 palmitoylation and increased localization of CD36 on the plasma membrane of hepatocytes were also observed in livers of mice with NASH. Furthermore, inhibition of CD36 palmitoylation protected mice from developing NASH. The absence of palmitoylation decreased CD36 protein hydrophobicity reducing its localization on the plasma membrane as well as in lipid raft of hepatocytes. Consequently, a lack of palmitoylation decreased fatty acid uptake and CD36/Fyn/Lyn complex in HepG2 cells. Inhibition of CD36 palmitoylation not only ameliorated intracellular lipid accumulation via activating the AMPK pathway, but also inhibited inflammatory response through the inhibition of the JNK signaling pathway. CONCLUSIONS: Our findings demonstrate the key role of palmitoylation in regulating CD36 distributions and its functions in NASH. Inhibition of CD36 palmitoylation may represent an effective therapeutic strategy in patients with NASH. LAY SUMMARY: Fatty acid translocase CD36 (CD36) is a multifunctional membrane protein which contributes to the development of liver steatosis. In the present study, we demonstrated that the localization of CD36 on the plasma membrane of hepatocytes is increased in patients with NASH. Blocking the palmitoylation of CD36 reduces CD36 distribution in hepatocytes plasma membrane and protects mice from NASH. The inhibition of CD36 palmitoylation not only improved fatty acid metabolic disorders but also reduced the inflammatory response in vitro and in vivo. The present study suggests that CD36 palmitoylation is important for NASH development and inhibition of CD36 palmitoylation could be used to cure NASH

Bipolar disorder and age-related functional impairment

OBJECTIVE: Although bipolar disorder is a major contributor to functional impairment worldwide, an independent impact of bipolar disorder and ageing on functioning has yet to be demonstrated. The objective of the present study was to evaluate the effect of bipolar disorder on age-related functional status using matched controls as a standard. METHOD: One-hundred patients with bipolar disorder and matched controls were evaluated for disability. Age-related effects controlled for confounders were cross-sectionally evaluated. RESULTS: Patients were significantly more impaired than controls. Regression showed effects for aging in both groups. The effect, size, however, was significantly stronger in patients. CONCLUSION: Bipolar disorder was an important effect modifier of the age impact on functioning. While a longitudinal design is needed to effectively demonstrate this different impact, this study further depicts bipolar disorder as a chronic and progressively impairing illness

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Staging Bipolar Disorder.

The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodromal (at-risk) to more severe and refractory presentations (Stage IV). A staging model implies a longitudinal appraisal of different aspects: clinical variables, such as number of episodes and subsyndromal symptoms, functional and cognitive impairment, comorbidity, biomarkers, and neuroanatomical changes. Staging models are based on the fact that response to treatment is generally better when it is introduced early in the course of the illness. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in bipolar disorder treatment planning and prognosis, and emphasize the importance of early intervention. Further research is required in this exciting and novel area

Shedding light on plant litter decomposition: Advances, implications and new directions in understanding the role of photodegradation

Litter decomposition contributes to one of the largest fluxes of carbon (C) in the terrestrial biosphere and is a primary control on nutrient cycling. The inability of models using climate and litter chemistry to predict decomposition in dry environments has stimulated investigation of non-traditional drivers of decomposition, including photodegradation, the abiotic decomposition of organic matter via exposure to solar radiation. Recent work in this developing field shows that photodegradation may substantially influence terrestrial C fluxes, including abiotic production of carbon dioxide, carbon monoxide and methane, especially in arid and semi-arid regions. Research has also produced contradictory results regarding controls on photodegradation. Here we summarize the state of knowledge about the role of photodegradation in litter decomposition and C cycling and investigate drivers of photodegradation across experiments using a meta-analysis. Overall, increasing litter exposure to solar radiation increased mass loss by 23% with large variation in photodegradation rates among and within ecosystems. This variation was tied to both litter and environmental characteristics. Photodegradation increased with litter C to nitrogen (N) ratio, but not with lignin content, suggesting that we do not yet fully understand the underlying mechanisms. Photodegradation also increased with factors that increased solar radiation exposure (latitude and litter area to mass ratio) and decreased with mean annual precipitation. The impact of photodegradation on C (and potentially N) cycling fundamentally reshapes our thinking of decomposition as a solely biological process and requires that we define the mechanisms driving photodegradation before we can accurately represent photodegradation in global C and N models. © 2012 US Government

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN