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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • Adams, Hieab H. H., et al. (författare)
  • Novel genetic loci underlying human intracranial volume identified through genome-wide association
  • 2016
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 19:12, s. 1569-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
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3.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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4.
  • Aad, G., et al. (författare)
  • The ATLAS Experiment at the CERN Large Hadron Collider
  • 2008
  • Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 3:S08003:3, s. S08003-
  • Forskningsöversikt (refereegranskat)abstract
    • The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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5.
  • Aad, G., et al. (författare)
  • A search for new physics in dijet mass and angular distributions in pp collisions at root s=7 TeV measured with the ATLAS detector
  • 2011
  • Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for new interactions and resonances produced in LHC proton-proton (pp) collisions at a centre-of-mass energy root s = 7 TeV was performed with the ATLAS detector. Using a dataset with an integrated luminosity of 36 pb(-1), dijet mass and angular distributions were measured up to dijet masses of similar to 3.5 TeV and were found to be in good agreement with Standard Model predictions. This analysis sets limits at 95% CL on various models for new physics: an excited quark is excluded for mass between 0.60 and 2.64 TeV, an axigluon hypothesis is excluded for axigluon masses between 0.60 and 2.10 TeV and quantum black holes are excluded in models with six extra space-time dimensions for quantum gravity scales between 0.75 and 3.67 TeV. Production cross section limits as a function of dijet mass are set using a simplified Gaussian signal model to facilitate comparisons with other hypotheses. Analysis of the dijet angular distribution using a novel technique simultaneously employing the dijet mass excludes quark contact interactions with a compositeness scale 3 below 9.5 TeV.
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6.
  • Aad, G., et al. (författare)
  • Charged-particle multiplicities in pp interactions at root s=900 GeV measured with the ATLAS detector at the LHC ATLAS Collaboration
  • 2010
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier. - 0370-2693 .- 1873-2445. ; 688:1, s. 21-42
  • Tidskriftsartikel (refereegranskat)abstract
    • The first measurements from proton-proton collisions recorded with the ATLAS detector at the LHC are presented. Data were collected in December 2009 using a minimum-bias trigger during collisions at a centre-of-mass energy of 900 GeV. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity, and the relationship between mean transverse momentum and charged-particle multiplicity are measured for events with at least one charged particle in the kinematic range vertical bar eta vertical bar < 2.5 and p(T) > 500 MeV. The measurements are compared to Monte Carlo models of proton-proton collisions and to results from other experiments at the same centre-of-mass energy. The charged-particle multiplicity per event and unit of pseudorapidity eta = 0 is measured to be 1.333 +/- 0.003(stat.) +/- 0.040(syst.), which is 5-15% higher than the Monte Carlo models predict. 2010 Published by Elsevier B.V.
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7.
  • Aad, G., et al. (författare)
  • Charged-particle multiplicities in pp interactions measured with the ATLAS detector at the LHC
  • 2011
  • Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements are presented from proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36 and 7 TeV recorded with the ATLAS detector at the LHC. Events were collected using a single-arm minimum-bias trigger. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transverse momentum and charged-particle multiplicity are measured. Measurements in different regions of phase space are shown, providing diffraction-reduced measurements as well as more inclusive ones. The observed distributions are corrected to well-defined phase-space regions, using model-independent corrections. The results are compared to each other and to various Monte Carlo (MC) models, including a new AMBT1 pythia6 tune. In all the kinematic regions considered, the particle multiplicities are higher than predicted by the MC models. The central charged-particle multiplicity per event and unit of pseudorapidity, for tracks with p(T) > 100 MeV, is measured to be 3.483 +/- 0.009 (stat) +/- 0.106 (syst) at root s = 0.9 TeV and 5.630 +/- 0.003 (stat) +/- 0.169 (syst) at root s = 7 TeV.
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8.
  • Aad, G., et al. (författare)
  • Luminosity determination in pp collisions at root s=7 TeV using the ATLAS detector at the LHC
  • 2011
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer. - 1434-6044 .- 1434-6052. ; 71:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of luminosity obtained using the ATLAS detector during early running of the Large Hadron Collider (LHC) at root s = 7 TeV are presented. The luminosity is independently determined using several detectors and multiple algorithms, each having different acceptances, systematic uncertainties and sensitivity to background. The ratios of the luminosities obtained from these methods are monitored as a function of time and of mu, the average number of inelastic interactions per bunch crossing. Residual time- and mu-dependence between the methods is less than 2% for 0 < mu < 2.5. Absolute luminosity calibrations, performed using beam separation scans, have a common systematic uncertainty of +/- 11%, dominated by the measurement of the LHC beam currents. After calibration, the luminosities obtained from the different methods differ by at most +/- 2%. The visible cross sections measured using the beam scans are compared to predictions obtained with the PYTHIA and PHOJET event generators and the ATLAS detector simulation.
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9.
  • Aad, G., et al. (författare)
  • Measurement of Dijet Azimuthal Decorrelations in pp Collisions at root s=7 TeV
  • 2011
  • Ingår i: Physical Review Letters. - : American Physical Society. - 1079-7114 .- 0031-9007. ; 106:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Azimuthal decorrelations between the two central jets with the largest transverse momenta are sensitive to the dynamics of events with multiple jets. We present a measurement of the normalized differential cross section based on the full data set ( integral Ldt = 36 pb(-1)) acquired by the ATLAS detector during the 2010 root s = 7 TeV proton-proton run of the LHC. The measured distributions include jets with transverse momenta up to 1.3 TeV, probing perturbative QCD in a high-energy regime.
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10.
  • Aad, G., et al. (författare)
  • Measurement of inclusive jet and dijet cross sections in proton-proton collisions at 7 TeV centre-of-mass energy with the ATLAS detector
  • 2011
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer. - 1434-6044 .- 1434-6052. ; 71:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Jet cross sections have been measured for the first time in proton-proton collisions at a centre-of-mass energy of 7 TeV using the ATLAS detector. The measurement uses an integrated luminosity of 17 nb(-1) recorded at the Large Hadron Collider. The anti-k(t) algorithm is used to identify jets, with two jet resolution parameters, R = 0.4 and 0.6. The dominant uncertainty comes from the jet energy scale, which is determined to within 7% for central jets above 60 GeV transverse momentum. Inclusive single-jet differential cross sections are presented as functions of jet transverse momentum and rapidity. Dijet cross sections are presented as functions of dijet mass and the angular variable chi. The results are compared to expectations based on next-to-leading-order QCD, which agree with the data, providing a validation of the theory in a new kinematic regime.
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