| 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. |
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| 5. |
- Lee, Chia-Lin, et al.
(författare)
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Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e37897-
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Tidskriftsartikel (refereegranskat)abstract
- In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08-1.66 mu g/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a-b and for the carbonyl group of 5-OCOCH3 in 7a-b, important for their cytotoxic properties. The SAR for moderately active 5a-b (5-OCH3), and highly active 6a-b and 7a-b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a-b as topoisomerase II inhibitors.
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| 6. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 7. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Chen, Chi-Kuan, et al.
(författare)
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Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment
- 2014
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Ingår i: Hepatology. - Hoboken : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 59:3, s. 974-985
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects.CONCLUSION: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer.
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| 16. |
- Dong, Yaa-Hui, et al.
(författare)
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Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and Influenza A Systematic Review and Meta-analysis of Randomized Controlled Trials
- 2014
-
Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 145:6, s. 1286-1297
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However the risks of other respiratory infections such as TB and influenza remain unclear. Methods: Through a comprehensive literature search of MEDLINE EMBASE CINAHL Cochrane Library and ClinicalTrials.gov from inception to July 2013 we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto Mantel-Haenszel and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza. Results: Twenty-five trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment ICS treatment was associated with a significantly higher risk of TB (Peto OR 2.29 95% CI 1.04-5.03) but not influenza (Peto OR 1.24 95% CI 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667 respectively). Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD which deserve further investigation.
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| 17. |
- Lin, Chang, et al.
(författare)
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Green aerator using periodically oscillatory flow generated inside a vertical dropping pool
- 2012
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Konferensbidrag (refereegranskat)abstract
- The flow conditions for generating periodically oscillatory flows and thus entraining a large amount of air bubbles into the water mass in a vertical dropping pool, which can be used potentially as a green aerator, were investigated experimentally. The approaching flows passing through upstream reach of a vertical dropping pool were studied under sub-critical condition. A wave gauge was used to measure the free surface fluctuations in the pool, and flow visualization technique was employed to reveal the flow structure of the dropping flows qualitatively. Under certain conditions, the falling flow over a vertical dropping pool forms a switching jet that oscillates up and down periodically and impinges on the bottom and the downstream corner of the pool alternately. The switching jet switches between an impinging jet (or napped flow) and a sliding jet (or skimming flow), causing it to oscillate periodically with a unique period and to entrain a large number of air bubbles into the switching jet, thus enhancing the dissolved oxygen quantity and turbulent mixing. The primary frequency of the periodic oscillation was determined by applying spectral analysis to the time history of wave-gauge measurements for the free surface elevation of the dropping flows. Variables influencing the fundamental oscillation frequency were carefully checked, and an empirical relation between a weighted Strouhal number and a grouped non-dimensional parameter was proposed to predict the primary frequency of the periodically oscillatory flow.
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| 18. |
- Neupane, Madhab, et al.
(författare)
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Observation of quantum-tunnelling-modulated spin texture in ultrathin topological insulator Bi2Se3 films.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the spin-texture behaviour of boundary modes in ultrathin topological insulator films is critically essential for the design and fabrication of functional nanodevices. Here, by using spin-resolved photoemission spectroscopy with p-polarized light in topological insulator Bi2Se3 thin films, we report tunnelling-dependent evolution of spin configuration in topological insulator thin films across the metal-to-insulator transition. We report a systematic binding energy- and wavevector-dependent spin polarization for the topological surface electrons in the ultrathin gapped-Dirac-cone limit. The polarization decreases significantly with enhanced tunnelling realized systematically in thin insulating films, whereas magnitude of the polarization saturates to the bulk limit faster at larger wavevectors in thicker metallic films. We present a theoretical model that captures this delicate relationship between quantum tunnelling and Fermi surface spin polarization. Our high-resolution spin-based spectroscopic results suggest that the polarization current can be tuned to zero in thin insulating films forming the basis for a future spin-switch nanodevice.
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| 19. |
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| 20. |
- Rundgren, Carl-Johan, 1973-, et al.
(författare)
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Are you SLiM? Developing an instrument for civic scientific literacy measurement(SLiM) based on media coverage
- 2012
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Ingår i: Public Understanding of Science. - : SAGE Publications. - 0963-6625 .- 1361-6609. ; 21:6, s. 759-773
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to develop an instrument to assess civic scientific literacy in media (SLiM). A total of 50 multiple-choice items were developed based on the 95 most common scientific terms appearing in media covering the subjects of biology (45.26%, 22 items), earth science (37.90%, 19 items), physics (11.58%, 6 items) and chemistry (5.26%, 3 items) in Taiwan. A total of 1034 students from three distinct groups (7th graders, 10th graders and undergraduates) were invited to participate in this study. The reliability of this instrument was 0.86 (KR20). The average difficulty of the SLiM ranged from 0.19 to 0.91, and the discrimination power is 0.1 to 0.59. According to participants’ performances on SLiM, it was revealed that 10th graders (Mean = 37.3±4.2) performed better than undergraduates (Mean = 33.0±5.5) and 7th graders (Mean = 26.7±8.3) with significant differences (p< .05).
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| 21. |
- Xu, Su-Yang, et al.
(författare)
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Hedgehog spin texture and Berry's phase tuning in a magnetic topological insulator
- 2012
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Ingår i: Nature Physics. - 1745-2473. ; 8:8, s. 616-622
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and control of spin degrees of freedom on the surfaces of topological materials are key to future applications as well as for realizing novel physics such as the axion electrodynamics associated with time-reversal (TR) symmetry breaking on the surface. We experimentally demonstrate magnetically induced spin reorientation phenomena simultaneous with a Dirac-metal to gapped-insulator transition on the surfaces of manganese-doped Bi2Se3 thin films. The resulting electronic groundstate exhibits unique hedgehog-like spin textures at low energies, which directly demonstrate the mechanics of TR symmetry breaking on the surface. We further show that an insulating gap induced by quantum tunnelling between surfaces exhibits spin texture modulation at low energies but respects TR invariance. These spin phenomena and the control of their Fermi surface geometrical phase first demonstrated in our experiments pave the way for the future realization of many predicted exotic magnetic phenomena of topological origin.
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| 22. |
- Aad, G., et al.
(författare)
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- 2014
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 90:4
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 25. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 74:10
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Tidskriftsartikel (refereegranskat)
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| 26. |
- Aad, G., et al.
(författare)
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- 2014
-
Tidskriftsartikel (refereegranskat)
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| 27. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 28. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 29. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 30. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 31. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 74:12
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 33. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 74:11
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Aad, G., et al.
(författare)
-
- 2014
-
Tidskriftsartikel (refereegranskat)
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| 35. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 36. |
- Aad, G., et al.
(författare)
-
- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :11
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :10
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Physical Review D. Particles and fields. - 0556-2821 .- 1089-4918. ; 90:11, s. 112006-
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Aad, G., et al.
(författare)
-
- 2014
-
Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9, s. 1-61
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Tidskriftsartikel (refereegranskat)
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| 40. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 41. |
- Aad, G., et al.
(författare)
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- 2014
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Tidskriftsartikel (refereegranskat)
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| 42. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 43. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 90:5
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Tidskriftsartikel (refereegranskat)
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| 44. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :10
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :11
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Tidskriftsartikel (refereegranskat)
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| 47. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 48. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 90:11
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Tidskriftsartikel (refereegranskat)
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| 49. |
- Aad, G., et al.
(författare)
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- 2014
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Tidskriftsartikel (refereegranskat)
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| 50. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :10
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Tidskriftsartikel (refereegranskat)
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