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| 2. |
- 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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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Liu, Si, et al.
(författare)
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Ligand modification to stabilize the cobalt complexes for water oxidation
- 2017
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Ingår i: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 42:50, s. 29716-29724
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Tidskriftsartikel (refereegranskat)abstract
- Ligand modifications with electron-withdrawing and electron-donating groups were applied to afford three novel mononuclear cobalt-based catalysts [Co(TPA-R)]2+ (TPA = tris(2-pyridylmethyl) amine; R = tri-α F, 1; R = tri-αOMe, 2; R = mono-αF, 3) for water oxidation. Characterization of the catalysts shows that steric and electronic factors play important roles in inhibiting spontaneous intermolecular dimerization of two cobalt centers, and influence the catalytic behavior. Complex 1 exhibits the best catalytic ability and stability, showing a good efficiency with TOF of 6.03 ± 0.02 mol (O2)/(mol (cat)*s) in photo-induced water oxidation experiments using Ru (bpy)3 2+ as photosensitizer and Na2S2O8 as electron acceptor. The bulky electron donating groups in 2 led to degradation of the complex and formation of CoOx particles acting as the real catalyst. Electron-withdrawing substituents on the TPA ligand can stabilize the catalyst under both electrochemical and photo-induced conditions, with the enhancement increasing with the number of the electron-withdrawing groups. © 2017 Hydrogen Energy Publications LLC.
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| 5. |
- Tang, Ting-Ting, et al.
(författare)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 8. |
- He, Mao Qiang, et al.
(författare)
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Phylogenomics, divergence times and notes of orders in Basidiomycota
- 2024
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Ingår i: Fungal Diversity. - 1560-2745 .- 1878-9129. ; 126, s. 127-406
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Tidskriftsartikel (refereegranskat)abstract
- Basidiomycota is one of the major phyla in the fungal tree of life. The outline of Basidiomycota provides essential taxonomic information for researchers and workers in mycology. In this study, we present a time-framed phylogenomic tree with 487 species of Basidiomycota from 127 families, 47 orders, 14 classes and four subphyla; we update the outline of Basidiomycota based on the phylogenomic relationships and the taxonomic studies since 2019; and we provide notes for each order and discuss the history, defining characteristics, evolution, justification of orders, problems, significance, and plates. Our phylogenomic analysis suggests that the subphyla diverged in a time range of 443–490 Myr (million years), classes in a time range of 312–412 Myr, and orders in a time range of 102–361 Myr. Families diverged in a time range of 50–289 Myr, 76–224 Myr, and 62–156 Myr in Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina, respectively. Based on the phylogenomic relationships and divergence times, we propose a new suborder Mycenineae in Agaricales to accommodate Mycenaceae. In the current outline of Basidiomycota, there are four subphyla, 20 classes, 77 orders, 297 families, and 2134 genera accepted. When building a robust taxonomy of Basidiomycota in the genomic era, the generation of molecular phylogenetic data has become relatively easier. Finding phenotypical characters, especially those that can be applied for identification and classification, however, has become increasingly challenging.
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| 9. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 10. |
- Liu, Rui, et al.
(författare)
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Associations of sleep timing and time in bed with dementia and cognitive decline among Chinese older adults : A cohort study
- 2022
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 70:11, s. 3138-3151
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Tidskriftsartikel (refereegranskat)abstract
- Background: The longitudinal associations of sleep timing and time in bed (TIB) with dementia and cognitive decline in older adults are unclear.Methods: This population-based cohort study used data from 1982 participants who were aged >= 60 years, free of dementia, and living in rural communities in western Shandong, China. At the baseline (2014) and follow-up (2018) examinations, sleep parameters were assessed using standard questionnaires. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the DSM-IV criteria, and the NIA-AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional-hazards models, and general linear models.Results: During the mean follow-up of 3.7 years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J-shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J-shaped association with mid-sleep time. When sleep parameters were categorized into tertiles, the multivariable-adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01-2.83) for baseline sleep duration >8 hours (vs. 7-8 h), 2.17 (1.22-3.87) for bedtime before 9 p.m. (vs. 10 p.m. or later), and 2.00 (1.23-3.24) for mid-sleep time before 1 a.m. (vs. 1-1.5 a.m.). Early bedtime and mid-sleep time were significantly associated with incident AD (HR range: 2.25-2.51; p < 0.05). Among individuals who were free of dementia at follow-up, baseline long TIB, early bedtime and mid-sleep time, early and late rise time, and prolonged TIB and advanced bedtime and mid-sleep time from baseline to follow-up were associated with a greater decline in MMSE score (p < 0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged 60-74 years.Conclusions: Long TIB and early sleep timing are associated with an increased risk of dementia, and the associations with greater cognitive decline are evident only among older people aged 60-74 years and men.
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