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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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6.
  • Wang, Zhaoming, et al. (författare)
  • 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
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • 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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7.
  • Ablikim, M., et al. (författare)
  • Search for invisible decays of omega and phi with J/psi data at BESIII
  • 2018
  • Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 98:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a data sample of (1310.6 +/- 7.0) x 10(6) J/psi events collected with the BESIII detector operating at the BEPCII collider, we perform the first experimental search for invisible decays of a light vector meson (V = omega, phi) via J/psi -> V-eta decays. The decay of eta -> pi(+)pi(-)pi(0) is utilized to tag the V meson decaying into the invisible final state. No evidence for a significant invisible signal is observed, and the upper limits on the ratio of branching fractions at the 90% confidence level are determined to be B(omega -> invisible)/B(omega -> pi(+)pi(-)pi(0)) < 8.1 x 10(-5) and B(phi -> invisible)/B(phi -> K+K-) < 3.4 x 10(-4). By using the world average values of B(omega -> pi(+)pi(-)pi(0) and B(phi -> K+K-,) the upper limits on the decay branching fractions at the 90% confidence level are set as B(omega -> invisible) < 7.3 x 10(-5) and B(phi -> invisible) < 1.7 x 10(-4), respectively.
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8.
  • Ablikim, M., et al. (författare)
  • First measurement of e(+)e(-) -> pK(S)(0)(n)over-barK(-) + c.c. above open charm threshold
  • 2018
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 98:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The process e(+)e(-) -> pK(S)(0)(n) over barK(-) + c.c. and its intermediate processes are studied for the first time, using data samples collected with the BESIII detector at BEPCII at center-of-mass energies of 3.773, 4.008, 4.226, 4.258, 4.358, 4.416, and 4.600 GeV, with a total integrated luminosity of 7.4 fb(-1). The Born cross section of e(+)e(-) -> pK(S)(0)(n) over barK(-) + c.c. is measured at each center-of-mass energy, but no significant resonant structure in the measured cross-section line shape between 3.773 and 4.600 GeV is observed. No evident structure is detected in the pK(-), nK(S)(0), pK(S)(0), nK(+), p (n) over bar, or (KSK-)-K-0 invariant mass distributions except for Lambda(1520). The Born cross sections of e(+)e(-) -> Lambda(1520)(n) over barK(S)(0) + c.c. and e(+)e(-) -> Lambda(1520)(p) over barK(+) + c.c. are measured, and the 90% confidence level upper limits on the Born cross sections of e(+)e(-) -> Lambda(1520)(Lambda) over bar (1520) are determined at the seven center-of-mass energies. There is an evident difference in line shape and magnitude of the measured cross sections between e(+)e(-) -> Lambda(1520)(-> pK(-))(n) over barK(S)(0) and e(+)e(-) -> pK-(Lambda) over bar (1520)(-> (n) over barK(S)(0)).
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9.
  • Ablikim, M., et al. (författare)
  • Observation of the Semileptonic Decay D-0 -> a(0)(980)(-)e(+)nu(e) and Evidence for D+ -> a(0)(980)(0)e(+)nu(e)
  • 2018
  • Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Using an e(+)e(-) collision data sample of 2.93 fb(-1) collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of D-0 -> a(0)(980)(-)e(+)nu(e) and evidence for D+ -> a(0)(980)(0)e(+)nu(e) with significances of 6.4 sigma and 2.9 sigma, respectively. The absolute branching fractions are determined to be B(D-0 -> a(0)(980)(-)e(+)nu(e)) x B(a(0)(980)(-) -> eta pi(-)) = [1.33(-0.29)(+0.33)(stat) +/- 0.09(syst)] x 10(-4) and B(D+ -> a(0)(980)(0)e(+)nu(e)) x B(a(0)(980)(0) -> eta pi(0)) = [1.66(-0.66)(+0.81)(stat) +/- 0.11(syst) x 10(-4). This is the first time the a(0)(980) meson has been measured in a D-0 semileptonic decay, which would open one more interesting page in the investigation of the nature of the puzzling a(0)(980) states.
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10.
  • Ablikim, M., et al. (författare)
  • Search for the rare decays D -> h(h((')))e(+) e(-)
  • 2018
  • Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We search for rare decays of D mesons to hadrons accompanied by an electron-positron pair (h(h((')))e(+)e(- )),using an e(+)e(-) collision sample corresponding to an integrated luminosity of 2.93 fb(-1) collected with the BESIII detector at root s = 3.773 GeV. No significant signals are observed, and the corresponding upper limits on the branching fractions at the 90% confidence level are determined. The sensitivities of the results are at the level of 10(-5)-10(-6), providing a large improvement over previous searches.
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