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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. |
- Gröger, Matthias, et al.
(författare)
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Coupled regional Earth system modeling in the Baltic Sea region
- 2021
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 12:3, s. 939-973
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Forskningsöversikt (refereegranskat)abstract
- Nonlinear responses to externally forced climate change are known to dampen or amplify the local climate impact due to complex cross-compartmental feedback loops in the Earth system. These feedbacks are less well represented in the traditional stand-alone atmosphere and ocean models on which many of today's regional climate assessments rely (e.g., EURO-CORDEX, NOSCCA and BACC II). This has promoted the development of regional climate models for the Baltic Sea region by coupling different compartments of the Earth system into more comprehensive models. Coupled models more realistically represent feedback loops than the information imposed on the region by prescribed boundary conditions and, thus, permit more degrees of freedom. In the past, several coupled model systems have been developed for Europe and the Baltic Sea region. This article reviews recent progress on model systems that allow two-way communication between atmosphere and ocean models; models for the land surface, including the terrestrial biosphere; and wave models at the air-sea interface and hydrology models for water cycle closure. However, several processes that have mostly been realized by one-way coupling to date, such as marine biogeochemistry, nutrient cycling and atmospheric chemistry (e.g., aerosols), are not considered here. In contrast to uncoupled stand-alone models, coupled Earth system models can modify mean near-surface air temperatures locally by up to several degrees compared with their stand-alone atmospheric counterparts using prescribed surface boundary conditions. The representation of small-scale oceanic processes, such as vertical mixing and sea-ice dynamics, appears essential to accurately resolve the air-sea heat exchange over the Baltic Sea, and these parameters can only be provided by online coupled high-resolution ocean models. In addition, the coupling of wave models at the ocean-atmosphere interface allows for a more explicit formulation of small-scale to microphysical processes with local feedbacks to water temperature and large-scale processes such as oceanic upwelling. Over land, important climate feedbacks arise from dynamical terrestrial vegetation changes as well as the implementation of land-use scenarios and afforestation/deforestation that further alter surface albedo, roughness length and evapotranspiration. Furthermore, a good representation of surface temperatures and roughness length over open sea and land areas is critical for the representation of climatic extremes such as heavy precipitation, storms, or tropical nights (defined as nights where the daily minimum temperature does not fall below 20gC), and these parameters appear to be sensitive to coupling. For the present-day climate, many coupled atmosphere-ocean and atmosphere-land surface models have demonstrated the added value of single climate variables, in particular when low-quality boundary data were used in the respective stand-alone model. This makes coupled models a prospective tool for downscaling climate change scenarios from global climate models because these models often have large biases on the regional scale. However, the coupling of hydrology models to close the water cycle remains problematic, as the accuracy of precipitation provided by atmosphere models is, in most cases, insufficient to realistically simulate the runoff to the Baltic Sea without bias adjustments. Many regional stand-alone ocean and atmosphere models are tuned to suitably represent present-day climatologies rather than to accurately simulate climate change. Therefore, more research is required into how the regional climate sensitivity (e.g., the models' response to a given change in global mean temperature) is affected by coupling and how the spread is altered in multi-model and multi-scenario ensembles of coupled models compared with uncoupled ones.
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