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- 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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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- 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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| 8. |
- Cao, Hong Min, et al.
(författare)
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A long-lived compact jet in the black hole X-ray binary candidate AT2019wey
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 657
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Tidskriftsartikel (refereegranskat)abstract
- AT2019wey is a transient discovered by the Asteroid Terrestrial-impact Last Alert System survey in December of 2019. Follow-up optical, radio, and X-ray observations led to classification of this source as a Galactic black hole X-ray binary candidate. We carried out one-epoch 6.7 GHz European Very Long Baseline Interferometry Network and two-epoch multi-frequency (1.6, 4.5, 6.7 GHz) Very Long Baseline Array observations within a year after its discovery. These observations reveal a fading and flat-spectrum radio source with no discernible motion. These features suggest the detection of a compact jet. The source appears resolved at milliarcsecond scales, and the source angular size versus frequency trend is consistent with scatter broadening. This allows us to constrain the lower limit of the source distance to 6 kpc if the scattering medium is in a Galactic spiral arm. For a source location at greater than 3 kpc, the estimated upper limit of the peculiar velocity suggests the asymmetric natal kick may have occurred during the black hole formation stage.
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| 9. |
- Cao, Hong Min, et al.
(författare)
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The loud and the quiet: Searching for radio counterparts of two radio-weak BL Lac candidates with VLBI
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society: Letters. - : Oxford University Press (OUP). - 1745-3925 .- 1745-3933. ; 482:1, s. L34-L39
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Tidskriftsartikel (refereegranskat)abstract
- BL Lac objects are known to have compact jets inclined to our line of sight at a small angle, showing prominent radio emission. Two radio-weak BL Lac candidates with no counterparts in current radio surveys were recently reported by Massaro et al. Both sources were selected as candidate low-energy counterparts of unassociated Fermi γ -ray sources. We carried out very long baseline interferometry (VLBI) observations with the European VLBI Network (EVN) at 5 GHz to explore their radio properties at the milliarcsecond (mas) scale. One target, J1410+7405, is clearly detected with the EVN. Its measured 5-GHz flux density, 2.4 mJy, is consistent with recent interferometricmeasurementswith theKarlG. JanskyVery LargeArray, suggesting that the radio emission is confined to the inner ≲10-mas region. J1410+7405 is therefore identified as a radio-loud jetted active galactic nucleus, and its brightness temperature exceeds ~109 K. Its properties are similar to those of other γ -ray-detected BL Lac objects. On the other hand, the second target, J0644+6031, remains undetected with the EVN with a 6s brightness upper limit of 0.12 mJy beam-1. This source is thus radio-quiet, confirming its peculiarity, or possibly questioning its BL Lac nature.
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