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- 2019
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Tidskriftsartikel (refereegranskat)
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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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- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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- Abeysinghe, Kasun S., et al.
(författare)
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Mercury flow through an Asian rice-based food web
- 2017
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Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 229, s. 219-228
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a globally-distributed pollutant, toxic to humans and animals. Emissions are particularly high in Asia, and the source of exposure for humans there may also be different from other regions, including rice as well as fish consumption, particularly in contaminated areas. Yet the threats Asian wildlife face in rice-based ecosystems are as yet unclear. We sought to understand how Hg flows through rice-based food webs in historic mining and non-mining regions of Guizhou, China. We measured total Hg (THg) and methylmercury (MeHg) in soil, rice, 38 animal species (27 for MeHg) spanning multiple trophic levels, and examined the relationship between stable isotopes and Hg concentrations. Our results confirm biomagnification of THg/MeHg, with a high trophic magnification slope. Invertivorous songbirds had concentrations of THg in their feathers that were 15x and 3x the concentration reported to significantly impair reproduction, at mining and non-mining sites, respectively. High concentrations in specialist rice consumers and in granivorous birds, the later as high as in piscivorous birds,, suggest rice is a primary source of exposure. Spiders had the highest THg concentrations among invertebrates and may represent a vector through which Hg is passed to vertebrates, especially songbirds. Our findings suggest there could be significant population level health effects and consequent biodiversity loss in sensitive ecosystems, like agricultural wetlands, across Asia, and invertivorous songbirds would be good subjects for further studies investigating this possibility.
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- Hang, Chang C., et al.
(författare)
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Automatic Tuning and Adaptation for PID Controllers—A Survey
- 1992
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Ingår i: Adaptive Systems in Control and Signal Processing 1992.
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Konferensbidrag (refereegranskat)abstract
- Adaptive techniques such as gain scheduling, automatic tuning and continuous adaptation have been used in industrial single-loop controllers for about ten years. This paper gives a survey of the different adaptive techniques, the underlying process models and control designs. The paper ends with an overview of industrial adaptive single-loop controllers.
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