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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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- 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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- Vandone, V., et al.
(författare)
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Global properties of K hindrance probed by the gamma decay of the warm rotating W-174 nucleus
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:3, s. 034312-
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Tidskriftsartikel (refereegranskat)abstract
- The K hindrance to the gamma decay is studied in the warm rotating W-174 nucleus, focusing on the weakening of the selection rules of the K quantum number with increasing excitation energy. W-174 was populated by the fusion reaction of Ti-50 (at 217 MeV) on a Te-128 target, and its gamma decay was detected by the AGATA Demonstrator array coupled to a BaF2 multiplicity filter at Laboratori Nazionali di Legnaro of INFN. A fluctuation analysis of gamma coincidence matrices gives a similar number of low-K and high-K discrete excited bands. The results are compared to simulations of the gamma-decay flow based on a microscopic cranked shell model at finite temperature in which the K mixing is governed by the interplay of Coriolis force with the residual interaction. Agreement between simulations and experiment is obtained only by hindering the E1 decay between low-K and high-K bands by an amount compatible with that determined by spectroscopic studies of K isomers in the same mass region, with a similar trend with excitation energy. The work indicates that K mixing due to temperature effects may play a leading role for the entire body of discrete excited bands, which probes the onset region of K weakening.
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| 19. |
- Yarime, Masaru, et al.
(författare)
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Dissipation and Recycling: What Losses, What Dissipation Impacts, and What Recycling Options?
- 2014
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Ingår i: Sustainable Phosphorus Management. - Dordrecht : Springer Netherlands. - 9789400772496 ; , s. 247-274
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter describes the activities in the Dissipation and Recycling Node of Global TraPs, a multistakeholder project on the sustainable management of the global phosphorus (P) cycle. Along the P supply and demand chain, substantial amounts are lost, notably in mining, processing, agriculture via soil erosion, food waste, manure, and sewage sludge. They are not only critical with respect to wasting an essential resource, but also contribute to severe environmental impacts such as eutrophication of freshwater ecosystems or the development of dead zones in oceans. The Recycling and Dissipation Node covers the phosphorus system from those points where phosphate-containing waste or losses have occurred or been produced by human excreta, livestock, and industries. This chapter describes losses and recycling efforts, identifies knowledge implementation and dissemination gaps as well as critical questions, and outlines potential transdisciplinary case studies. Two pathways toward sustainable P management are in focus: To a major goal of sustainable P management therefore must be to (1) quantify P stocks and flows in order to (2) identify key areas for minimizing losses and realizing recycling opportunities. Several technologies already exist to recycle P from different sources, including manure, food waste, sewage, and steelmaking slag; however, due to various factors such as lacking economic incentives, insufficient regulations, technical obstacles, and missing anticipation of unintended impacts, only a minor part of potential secondary P resources has been utilized. Minimizing losses and increasing recycling rates as well as reducing unintended environmental impacts triggered by P dissipation require a better understanding of the social, technological, and economic rationale as well as the intrinsic interrelations between nutrient cycling and ecosystem stability. A useful approach will be to develop new social business models integrating innovative technologies, corporate strategies, and public policies. That requires intensive collaboration between different scientific disciplines and, most importantly, among a variety of key stakeholders, including industry, farmers, and government agencies.
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