| 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. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 3. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 4. |
- Aamodt, K., et al.
(författare)
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Charged-Particle Multiplicity Density at Midrapidity in Central Pb-Pb Collisions at root s(NN)=2.76 TeV
- 2010
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Ingår i: Physical Review Letters. - 1079-7114. ; 105:25
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Tidskriftsartikel (refereegranskat)abstract
- The first measurement of the charged-particle multiplicity density at midrapidity in Pb-Pb collisions at a center-of-mass energy per nucleon pair root s(NN) = 2.76 TeV is presented. For an event sample corresponding to the most central 5% of the hadronic cross section, the pseudorapidity density of primary charged particles at midrapidity is 1584 +/- 4(stat) +/- 76(syst), which corresponds to 8.3 +/- 0.4(syst) per participating nucleon pair. This represents an increase of about a factor 1.9 relative to pp collisions at similar collision energies, and about a factor 2.2 to central Au-Au collisions at root s(NN) = 0.2 TeV. This measurement provides the first experimental constraint for models of nucleus-nucleus collisions at LHC energies.
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| 5. |
- Aamodt, K., et al.
(författare)
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Elliptic Flow of Charged Particles in Pb-Pb Collisions at root s(NN)=2.76 TeV
- 2010
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Ingår i: Physical Review Letters. - 1079-7114. ; 105:25
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Tidskriftsartikel (refereegranskat)abstract
- We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at root s(NN) p = 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (vertical bar eta vertical bar < 0.8) and transverse momentum range 0.2 < p(t) < 5.0 GeV/c. The elliptic flow signal v(2), measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 +/- 0.002(stat) +/- 0.003(syst) in the 40%-50% centrality class. The differential elliptic flow v(2)(p(t)) reaches a maximum of 0.2 near p(t) = 3 GeV/c. Compared to RHIC Au-Au collisions at root s(NN) = 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.
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| 6. |
- Aamodt, K., et al.
(författare)
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Harmonic decomposition of two particle angular correlations in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2012
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 708:3-5, s. 249-264
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between unidentified charged trigger (t) and associated (a) particles are measured by the ALICE experiment in Pb-Pb collisions at root s(NN) = 2.76 TeV for transverse momenta 0.25 < p(T)(t,a) < 15 GeV/c, where p(T)(t) > p(T)(a). The shapes of the pair correlation distributions are studied in a variety of collision centrality classes between 0 and 50% of the total hadronic cross section for particles in the pseudorapidity interval |eta| < 1.0. Distributions in relative azimuth Delta phi equivalent to phi(t) - phi(a) are analyzed for |Delta eta| equivalent to |eta(t) - eta(a)| > 0.8, and are referred to as "long-range correlations". Fourier components V-n Delta equivalent to < cos(n Delta phi)> are extracted from the long-range azimuthal correlation functions. If particle pairs are correlated to one another through their individual correlation to a common symmetry plane, then the pair anisotropy V-n Delta (p(T)(t), p(T)(a)) is fully described in terms of single-particle anisotropies v(n)(p(T)) as V-n Delta(p(T)(t), p(T)(a)) = v(n)(p(T)(t))v(n)(p(T)(a)). This expectation is tested for 1 <= n <= 5 by applying a global fit of all V-n Delta(p(T)(t), p(T)(a)) to obtain the best values v(n){GF}(p(T)). It is found that for 2 <= n <= 5, the fit agrees well with data up to p(T)(a) similar to 3-4 GeV/c, with a trend of increasing deviation as p(T)(t) and p(T)(a) are increased or as collisions become more peripheral. This suggests that no pair correlation harmonic can be described over the full 0.25 < p(T) < 15 GeV/c range using a single v(n)(p(T)) curve: such a description is however approximately possible for 2 <= n <= 5 when p(T)(a) < 4 GeV/c. For the n = 1 harmonic, however, a single v(1)(p(T)) curve is not obtained even within the reduced range p(T)(a) < 4 GeV/c. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.
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| 7. |
- Aamodt, K., et al.
(författare)
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Higher Harmonic Anisotropic Flow Measurements of Charged Particles in Pb-Pb Collisions at root s(NN)=2.76 TeV
- 2011
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Ingår i: Physical Review Letters. - 1079-7114. ; 107:3
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of the triangular nu(3), quadrangular nu(4), and pentagonal nu(5) charged particle flow in Pb-Pb collisions at root s(NN) = 2.76 TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show that the triangular flow can be described in terms of the initial spatial anisotropy and its fluctuations, which provides strong constraints on its origin. In the most central events, where the elliptic flow nu(2) and nu(3) have similar magnitude, a double peaked structure in the two-particle azimuthal correlations is observed, which is often interpreted as a Mach cone response to fast partons. We show that this structure can be naturally explained from the measured anisotropic flow Fourier coefficients.
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| 8. |
- Aamodt, K., et al.
(författare)
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Particle-Yield Modification in Jetlike Azimuthal Dihadron Correlations in Pb-Pb Collisions at root S-NN=2.76 TeV
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 108:9
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Tidskriftsartikel (refereegranskat)abstract
- The yield of charged particles associated with high-pt trigger particles (8 < p(t) < 15 GeV/c) is measured with the ALICE detector in Pb-Pb collisions at root S-NN = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jetlike correlation peaks in azimuthal dihadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta p(t) > 3 GeV/c on the away side drops to about 60% of that observed in pp collisions, while on the near side a moderate enhancement of 20%-30% is found.
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| 9. |
- Aamodt, K., et al.
(författare)
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Rapidity and transverse momentum dependence of inclusive J/psi production in pp collisions at root s=7 TeV
- 2011
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 704:5, s. 442-455
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rapidities in pp collisions at root s = 7 TeV. In this Letter, we report on the first results obtained detecting the J/psi through the dilepton decay into e(+)e(-) and mu(+)mu(-) pairs in the rapidity ranges vertical bar y vertical bar < 0.9 and 2.5 < y < 4, respectively, and with acceptance down to zero PT. In the dielectron channel the analysis was carried Out on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1) and the number of signal events is N-J/psi = 352 +/- 32 (stat.) +/- 28 (syst.): the corresponding figures in the dimuon channel are L-int = 15.6 nb(-1) and N-J/psi = 1924 +/- 77 (stat.) +/- 144 (syst.). The measured production cross sections are sigma(J/psi) (vertical bar y vertical bar < 0.9) = 10.7 +/- 1.0 (stat.) +/- 1.6 (syst.)(-2.3)(+1.6) (syst.pol.) mu b and sigma(J/psi) (2.5 < y < 4) = 6.31 +/- 0.25 (stat.) +/- 0.76 (syst.)(-1.96)(+0.95) (syst.pol.) mu b. The differential cross sections, in transverse momentum and rapidity, of the J/psi were also measured. (C) 2011 CERN. Published by Elsevier B.V. All rights reserved.
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| 10. |
- Abbas, E., et al.
(författare)
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Centrality dependence of the pseudorapidity density distribution for charged particles in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 726:4-5, s. 610-622
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Tidskriftsartikel (refereegranskat)abstract
- We present the first wide-range measurement of the charged-particle pseudorapidity density distribution, for different centralities (the 0-5%, 5-10%, 10-20%, and 20-30% most central events) in Pb-Pb collisions at root s(NN) = 2.76 TeV at the LHC. The measurement is performed using the full coverage of the ALICE detectors, -5.0 < eta < 5.5, and employing a special analysis technique based on collisions arising from LHC 'satellite' bunches. We present the pseudorapidity density as a function of the number of participating nucleons as well as an extrapolation to the total number of produced charged particles (N-ch = 17165 +/- 772 for the 0-5% most central collisions). From the measured dN(ch)/d eta distribution we derive the rapidity density distribution, dN(ch)/dy, under simple assumptions. The rapidity density distribution is found to be significantly wider than the predictions of the Landau model. We assess the validity of longitudinal scaling by comparing to lower energy results from RHIC. Finally the mechanisms of the underlying particle production are discussed based on a comparison with various theoretical models. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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