| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
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| 4. |
- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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| 5. |
- Tang, Ting-Ting, et al.
(författare)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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| 6. |
- Abelev, B., et al.
(författare)
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Centrality, rapidity and transverse momentum dependence of J/Psi suppression in Pb-Pb collisions at root(NN)-N-S=2.76TeV
- 2014
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 734, s. 314-327
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Tidskriftsartikel (refereegranskat)abstract
- The inclusive J/.nuclear modification factor (R-AA) in Pb-Pb collisions at root(NN)-N-S = 2.76TeVhas been measured by ALICE as a function of centrality in the e+ e-decay channel at mid-rapidity (| y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the + -decay channel at forward-rapidity (2.5 < y < 4). The J/.yields measured in Pb-Pb are suppressed compared to those in ppcollisions scaled by the number of binary collisions. The RAAintegrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 - 0.06(stat.) - 0.10(syst.) at mid-rapidity and 0.58 - 0.01(stat.) - 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAAare measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/.yield originates from charm quark (re) combination in the deconfined partonic medium. (C) 2014 The Authors. Published by Elsevier B. V.
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| 7. |
- Abelev, B, et al.
(författare)
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Directed Flow of Charged Particles at Midrapidity Relative to the Spectator Plane in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:23
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Tidskriftsartikel (refereegranskat)abstract
- The directed flow of charged particles at midrapidity is measured in Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV relative to the collision symmetry plane defined by the spectator nucleons. A negative slope of the rapidity-odd directed flow component with approximately 3 times smaller magnitude than found at the highest RHIC energy is observed. This suggests a smaller longitudinal tilt of the initial system and disfavors the strong fireball rotation predicted for the LHC energies. The rapidity-even directed flow component is measured for the first time with spectators and found to be independent of pseudorapidity with a sign change at transverse momenta p_{T} between 1.2 and 1.7 GeV/c. Combined with the observation of a vanishing rapidity-even p_{T} shift along the spectator deflection this is strong evidence for dipolelike initial density fluctuations in the overlap zone of the nuclei. Similar trends in the rapidity-even directed flow and the estimate from two-particle correlations at midrapidity, which is larger by about a factor of 40, indicate a weak correlation between fluctuating participant and spectator symmetry planes. These observations open new possibilities for investigation of the initial conditions in heavy-ion collisions with spectator nucleons.
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| 8. |
- Abelev, B., et al.
(författare)
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Energy dependence of the transverse momentum distributions of charged particles in pp collisions measured by ALICE
- 2013
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:12
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Tidskriftsartikel (refereegranskat)abstract
- Differential cross sections of charged particles in inelastic pp collisions as a function of pT have been measured at root s = 0.9, 2.76 and 7 TeV at the LHC. The pT spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual root s cannot be described by NLO-pQCD, the relative increase of cross section with root s is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at root s = 2.76 and 5.02 TeV up to pT = 50 GeV/c as required for the calculation of the nuclear modification factor in nucleus-nucleus and proton-nucleus collisions.
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| 9. |
- Abelev, B., et al.
(författare)
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Freeze-out radii extracted from three-pion cumulants in pp, p-Pb and Pb-Pb collisions at the LHC
- 2014
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 739, s. 139-151
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Tidskriftsartikel (refereegranskat)abstract
- In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose-Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e. g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p-Pb and Pb-Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p-Pb collisions are found to be 5-15% larger than those in pp, while those in Pb-Pb are 35-55% larger than those in p-Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p-Pb as compared to pp collisions at similar multiplicity. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
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| 10. |
- Abelev, B., et al.
(författare)
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J/psi production and nuclear effects in p-Pb collisions at=5.02 TeV
- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- Inclusive J/psi production has been studied with the ALICE detector in p-Pb collisions at the nucleon-nucleon center of mass energy = 5.02 TeV at the CERN LHC. The measurement is performed in the center of mass rapidity domains 2.03 < y (cms) < 3.53 and -4.46 < y (cms) < -2.96, down to zero transverse momentum, studying the mu (+) mu (-) decay mode. In this paper, the J/psi production cross section and the nuclear modification factor R (pPb) for the rapidities under study are presented. While at forward rapidity, corresponding to the proton direction, a suppression of the J/psi yield with respect to binary-scaled pp collisions is observed, in the backward region no suppression is present. The ratio of the forward and backward yields is also measured differentially in rapidity and transverse momentum. Theoretical predictions based on nuclear shadowing, as well as on models including, in addition, a contribution from partonic energy loss, are in fair agreement with the experimental results.
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