| 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. |
- Liu, Ke, et al.
(författare)
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X Chromosome Dose and Sex Bias in Autoimmune Diseases
- 2016
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Ingår i: Arthritis & Rheumatology. - : WILEY-BLACKWELL. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300
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Tidskriftsartikel (refereegranskat)abstract
- Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.
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| 3. |
- Olefeldt, David, et al.
(författare)
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The Boreal-Arctic Wetland and Lake Dataset (BAWLD)
- 2021
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Ingår i: Earth System Science Data. - : Copernicus Gesellschaft MBH. - 1866-3508 .- 1866-3516. ; 13:11, s. 5127-5149
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Tidskriftsartikel (refereegranskat)abstract
- Methane emissions from boreal and arctic wetlands, lakes, and rivers are expected to increase in response to warming and associated permafrost thaw. However, the lack of appropriate land cover datasets for scaling field-measured methane emissions to circumpolar scales has contributed to a large uncertainty for our understanding of present-day and future methane emissions. Here we present the BorealArctic Wetland and Lake Dataset (BAWLD), a land cover dataset based on an expert assessment, extrapolated using random forest modelling from available spatial datasets of climate, topography, soils, permafrost conditions, vegetation, wetlands, and surface water extents and dynamics. In BAWLD, we estimate the fractional coverage of five wetland, seven lake, and three river classes within 0.5 x 0.5 degrees grid cells that cover the northern boreal and tundra biomes (17 % of the global land surface). Land cover classes were defined using criteria that ensured distinct methane emissions among classes, as indicated by a co-developed comprehensive dataset of methane flux observations. In BAWLD, wetlands occupied 3.2 x 10(6) km(2) (14 % of domain) with a 95 % confidence interval between 2.8 and 3.8 x 10(6) km(2). Bog, fen, and permafrost bog were the most abundant wetland classes, covering similar to 28 % each of the total wetland area, while the highest-methane-emitting marsh and tundra wetland classes occupied 5 % and 12 %, respectively. Lakes, defined to include all lentic open-water ecosystems regardless of size, covered 1.4 x 10(6) km(2) (6 % of domain). Low-methane-emitting large lakes (>10 km(2)) and glacial lakes jointly represented 78 % of the total lake area, while high-emitting peatland and yedoma lakes covered 18 % and 4 %, respectively. Small (<0.1 km(2)) glacial, peatland, and yedoma lakes combined covered 17 % of the total lake area but contributed disproportionally to the overall spatial uncertainty in lake area with a 95 % confidence interval between 0.15 and 0.38 x 10(6) km(2). Rivers and streams were estimated to cover 0.12 x 10(6) km(2) (0.5 % of domain), of which 8 % was associated with high-methane-emitting headwaters that drain organic-rich landscapes. Distinct combinations of spatially co-occurring wetland and lake classes were identified across the BAWLD domain, allowing for the mapping of "wetscapes" that have characteristic methane emission magnitudes and sensitivities to climate change at regional scales. With BAWLD, we provide a dataset which avoids double-accounting of wetland, lake, and river extents and which includes confidence intervals for each land cover class. As such, BAWLD will be suitable for many hydrological and biogeochemical modelling and upscaling efforts for the northern boreal and arctic region, in particular those aimed at improving assessments of current and future methane emissions.
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