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2.
  • 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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3.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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4.
  • Adare, A., et al. (författare)
  • Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review Letters. - : American Physical Society. - 1079-7114. ; 115:14
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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5.
  • Adare, A., et al. (författare)
  • Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 91:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
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6.
  • Adare, A., et al. (författare)
  • Centrality dependence of low-momentum direct-photon production in Au plus Au collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 91:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX experiment at RHIC has measured the centrality dependence of the direct photon yield from Au + Au collisions at root s(NN) = 200 GeV down to pT = 0.4 GeV/c. Photons are detected via photon conversions to e(+)e(-) pairs and an improved technique is applied that minimizes the systematic uncertainties that usually limit direct photon measurements, in particular at low pT. We find an excess of direct photons above the N-coll-scaled yield measured in p + p collisions. This excess yield is well described by an exponential distribution with an inverse slope of about 240 MeV/c in the pT range 0.6-2.0 GeV/c. While the shape of the pT distribution is independent of centrality within the experimental uncertainties, the yield increases rapidly with increasing centrality, scaling approximately with N-part(alpha), where alpha = 1.38 +/- 0.03(stat) +/- 0.07(syst).
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7.
  • Adare, A., et al. (författare)
  • Direct photon production in d+Au collisions at root s(NN)=200 GeV
  • 2013
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 87:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Direct photons have been measured in root s(NN) = 200 GeV d + Au collisions at midrapidity. A wide p(T) range is covered by measurements of nearly real virtual photons (1 < p(T) < 6 GeV/c) and real photons (5 < p(T) < 16 GeV/c). The invariant yield of the direct photons in d + Au collisions over the scaled p + p cross section is consistent with unity. Theoretical calculations assuming standard cold-nuclear-matter effects describe the data well for the entire p(T) range. This indicates that the large enhancement of direct photons observed in Au + Au collisions for 1.0 < p(T) < 2.5 GeV/c is attributable to a source other than the initial-state nuclear effects.
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8.
  • Adare, A., et al. (författare)
  • Measurement of gamma(1S+2S+3S) production in p plus p and Au plus Au collisions at root sNN=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 91:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of bottomonium production in heavy-ion and p + p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three states, (1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au + Au and p + p collisions at root sNN = 200 GeV. The (1S + 2S + 3S) -> e(+)e(-) differential cross section at midrapidity was found to be B(ee)d sigma/dy = 108 +/- 38 (stat) +/- 15 (syst) +/- 11 (luminosity) pb in p + p collisions. The nuclear modification factor in the 30% most central Au + Au collisions indicates a suppression of the total. state yield relative to the extrapolation from p + p collision data. The suppression is consistent with measurements made by STAR at RHIC and at higher energies by the CMS experiment at the Large Hadron Collider.
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9.
  • Adare, A., et al. (författare)
  • Measurement of higher cumulants of net-charge multiplicity distributions in Au plus Au collisions at root s(NN)=7.7-200 GeV
  • 2016
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 93:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the measurement of cumulants (C-n,n = 1, ..., 4) of the net-charge distributions measured within pseudorapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(NN) = 7.7-200 GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g., C-1/C-2, C-3/C-1) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of C-1/C-2 and C-3/C-1 can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy. The extracted baryon chemical potentials are in excellent agreement with a thermal-statistical analysis model.
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10.
  • Adare, A., et al. (författare)
  • Measurement of K-S(0) and K*(0) in p plus p, d plus Au, and Cu plus Cu collisions at root s(NN)=200 GeV
  • 2014
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813. ; 90:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K-S(0) and K*(0) meson production at midrapidity in p + p, d + Au, and Cu + Cu collisions at root s(NN) = 200 GeV. The K-S(0) and K*(0) mesons are reconstructed via their K-S(0) -> pi(0)(-> gamma gamma) pi(0)(-> gamma gamma) and K*(0) -> K-+/-pi(-/+) decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K-S(0) and K*(0) mesons in d + Au and Cu + Cu collisions at different centralities. In the d + Au collisions, the nuclear modification factor of K-S(0) and K*(0) mesons is almost constant as a function of transverse momentum and is consistent with unity, showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu + Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p + p yield scaled by the number of binary nucleon-nucleon collisions in the Cu + Cu system. In the p(T) range 2-5 GeV/c, the strange mesons (K-S(0), K*(0)) similarly to the phi meson with hidden strangeness, showan intermediate suppression between the more suppressed light quark mesons (pi(0)) and the nonsuppressed baryons (p, (p) over bar). At higher transverse momentum, p(T) > 5 GeV/c, production of all particles is similarly suppressed by a factor of approximate to 2.
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