Species-specific kinetics and zonation of hepatic DNA synthesis induced by ligands of PPAR?

PPAR? ligands evoke a profound mitogenic response in rodent liver, and the aim of this studywas to characterise the kinetics of induction of DNA synthesis. The CAR ligand, 1,4-bis[2-(3,5-dichoropyridyloxy)]benzene, caused induction of hepatocyte DNA synthesis within 48 hours in129S4/SvJae mice, but the potent PPAR? ligand, ciprofibrate, induced hepatocyte DNA synthesisonly after 3 or 4 days dosing; higher or lower doses did not hasten the DNA synthesisresponse. This contrasted with the rapid induction (24 hours) reported by Styles et al. (Carcinogenesis9:1647-1655). C57BL/6 and DBA/2J mice showed significant induction of DNA synthesisafter 4, but not 2, days ciprofibrate treatment. Alderley Park and 129S4/SvJae mice dosedwith methylclofenapate induced hepatocyte DNA synthesis at 4, but not 2, days after dosing,and proved that inconsistency with prior work was not due to a difference in mouse strain orPPAR? ligand. Ciprofibrate-induced liver DNA synthesis and growth was absent in PPAR?-null mice, and are PPAR?-dependent. In the Fisher344 rat, hepatocyte DNA synthesis was inducedat 24 hours after dosing, with a second peak at 48 hours. Lobular localisation of hepatocyteDNA synthesis showed preferential periportal induction of DNA synthesis in rat, butpanlobular zonation of hepatocyte DNA synthesis in mouse. These results characterise a markedlylater hepatic induction of panlobular DNA synthesis by PPAR? ligands in mouse, comparedto rapid induction of periportal DNA synthesis in rat

Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy