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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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| 2. |
- Burney, Peter, et al.
(författare)
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Chronic obstructive pulmonary disease mortality and prevalence : the associations with smoking and poverty-a BOLD analysis
- 2014
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:5, s. 465-473
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). Methods National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. Results National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men r(s)=0.73, p=0.0001; women r(s)=0.90, p<0.0001; 60+ years: men r(s)=0.63, p=0.0022; women r(s)=0.37, p=0.1) than obstruction (<60 years: men r(s)=0.28, p=0.20; women r(s)=0.17, p<0.46; 60+ years: men r(s)=0.28, p=0.23; women r(s)=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$ 15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$ 15 000. Conclusions Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.
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| 5. |
- Tang, Shi, et al.
(författare)
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Small-molecule light-emitting electrochemical cells : evidence for in situ electrochemical doping and functional operation
- 2013
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 49:43, s. 4926-4928
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that non-ionic small molecules (SMs) can function as the doping and emissive compound in light-emitting electrochemical cells (LECs), and that high brightness and decent efficiency can be attained for such devices. It is plausible that the expansion of the LEC library, to include easy-to-purify and tunable non-ionic SM compounds, could represent a viable path towards improved LEC devices.
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| 6. |
- 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. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (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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