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. |
- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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4. |
- Cheung, William W. L., et al.
(författare)
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Building confidence in projections of the responses of living marine resources to climate change
- 2016
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Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 73:5, s. 1283-1296
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Tidskriftsartikel (refereegranskat)abstract
- The Fifth Assessment Report of the Intergovernmental Panel on Climate Change highlights that climate change and ocean acidification are challenging the sustainable management of living marine resources (LMRs). Formal and systematic treatment of uncertainty in existing LMR projections, however, is lacking. We synthesize knowledge of how to address different sources of uncertainty by drawing from climate model intercomparison efforts. We suggest an ensemble of available models and projections, informed by observations, as a starting point to quantify uncertainties. Such an ensemble must be paired with analysis of the dominant uncertainties over different spatial scales, time horizons, and metrics. We use two examples: (i) global and regional projections of Sea Surface Temperature and (ii) projection of changes in potential catch of sablefish (Anoplopoma fimbria) in the 21st century, to illustrate this ensemble model approach to explore different types of uncertainties. Further effort should prioritize understanding dominant, undersampled dimensions of uncertainty, as well as the strategic collection of observations to quantify, and ultimately reduce, uncertainties. Our proposed framework will improve our understanding of future changes in LMR and the resulting risk of impacts to ecosystems and the societies under changing ocean conditions.
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5. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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6. |
- Eddy, Tyler D., et al.
(författare)
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Energy Flow Through Marine Ecosystems : Confronting Transfer Efficiency
- 2021
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 36:1, s. 76-86
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Forskningsöversikt (refereegranskat)abstract
- Transfer efficiency is the proportion of energy passed between nodes in food webs. It is an emergent, unitless property that is difficult to measure, and responds dynamically to environmental and ecosystem changes. Because the consequences of changes in transfer efficiency compound through ecosystems, slight variations can have large effects on food availability for top predators. Here, we review the processes controlling transfer efficiency, approaches to estimate it, and known variations across ocean biomes. Both process-level analysis and observed macro-scale variations suggest that ecosystem-scale transfer efficiency is highly variable, impacted by fishing, and will decline with climate change. It is important that we more fully resolve the processes controlling transfer efficiency in models to effectively anticipate changes in marine ecosystems and fisheries resources.
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7. |
- Frieler, Katja, et al.
(författare)
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Scenario setup and forcing data for impact model evaluation and impact attribution within the third round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a)
- 2024
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Ingår i: Geoscientific Model Development. - : Copernicus Publications. - 1991-959X .- 1991-9603. ; 17:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the rationale and the protocol of the first component of the third simulation round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a, http://www.isimip.org, last access: 2 November 2023) and the associated set of climate-related and direct human forcing data (CRF and DHF, respectively). The observation-based climate-related forcings for the first time include high-resolution observational climate forcings derived by orographic downscaling, monthly to hourly coastal water levels, and wind fields associated with historical tropical cyclones. The DHFs include land use patterns, population densities, information about water and agricultural management, and fishing intensities. The ISIMIP3a impact model simulations driven by these observation-based climate-related and direct human forcings are designed to test to what degree the impact models can explain observed changes in natural and human systems. In a second set of ISIMIP3a experiments the participating impact models are forced by the same DHFs but a counterfactual set of atmospheric forcings and coastal water levels where observed trends have been removed. These experiments are designed to allow for the attribution of observed changes in natural, human, and managed systems to climate change, rising CH4 and CO2 concentrations, and sea level rise according to the definition of the Working Group II contribution to the IPCC AR6.
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8. |
- Lotze, Heike K., et al.
(författare)
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Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:26, s. 12907-12912
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Tidskriftsartikel (refereegranskat)abstract
- While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (+/- 4% SD) under low emissions and 17% (+/- 11% SD) under high emissions by 2100, with an average 5% decline for every 1 degrees C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.
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9. |
- Tang, Weiyi, et al.
(författare)
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Database of nitrification and nitrifiers in the global ocean
- 2023
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Ingår i: EARTH SYSTEM SCIENCE DATA. - 1866-3508 .- 1866-3516. ; 15:11, s. 5039-5077
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Tidskriftsartikel (refereegranskat)abstract
- As a key biogeochemical pathway in the marine nitrogen cycle, nitrification (ammonia oxidation and nitrite oxidation) converts the most reduced form of nitrogen - ammonium-ammonia (NH-NH3) - into the oxidized species nitrite (NO) and nitrate (NO). In the ocean, these processes are mainly performed by ammonia-oxidizing archaea (AOA) and bacteria (AOB) and nitrite-oxidizing bacteria (NOB). By transforming nitrogen speciation and providing substrates for nitrogen removal, nitrification affects microbial community structure; marine productivity (including chemoautotrophic carbon fixation); and the production of a powerful greenhouse gas, nitrous oxide (N2O). Nitrification is hypothesized to be regulated by temperature, oxygen, light, substrate concentration, substrate flux, pH and other environmental factors. Although the number of field observations from various oceanic regions has increased considerably over the last few decades, a global synthesis is lacking, and understanding how environmental factors control nitrification remains elusive. Therefore, we have compiled a database of nitrification rates and nitrifier abundance in the global ocean from published literature and unpublished datasets. This database includes 2393 and 1006 measurements of ammonia oxidation and nitrite oxidation rates and 2242 and 631 quantifications of ammonia oxidizers and nitrite oxidizers, respectively. This community effort confirms and enhances our understanding of the spatial distribution of nitrification and nitrifiers and their corresponding drivers such as the important role of substrate concentration in controlling nitrification rates and nitrifier abundance. Some conundrums are also revealed, including the inconsistent observations of light limitation and high rates of nitrite oxidation reported from anoxic waters. This database can be used to constrain the distribution of marine nitrification, to evaluate and improve biogeochemical models of nitrification, and to quantify the impact of nitrification on ecosystem functions like marine productivity and N2O production. This database additionally sets a baseline for comparison with future observations and guides future exploration (e.g., measurements in the poorly sampled regions such as the Indian Ocean and method comparison and/or standardization). The database is publicly available at the Zenodo repository: https://doi.org/10.5281/zenodo.8355912 (Tang et al., 2023).
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10. |
- Tittensor, Derek P., et al.
(författare)
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A protocol for the intercomparison of marine fishery and ecosystem models : Fish-MIP v1.0
- 2018
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 11:4, s. 1421-1442
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Tidskriftsartikel (refereegranskat)abstract
- Model intercomparison studies in the climate and Earth sciences communities have been crucial to building credibility and coherence for future projections. They have quantified variability among models, spurred model development, contrasted within- and among-model uncertainty, assessed model fits to historical data, and provided ensemble projections of future change under specified scenarios. Given the speed and magnitude of anthropogenic change in the marine environment and the consequent effects on food security, biodiversity, marine industries, and society, the time is ripe for similar comparisons among models of fisheries and marine ecosystems. Here, we describe the Fisheries and Marine Ecosystem Model Intercomparison Project protocol version 1.0 (Fish-MIP v1.0), part of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP), which is a cross-sectoral network of climate impact modellers. Given the complexity of the marine ecosystem, this class of models has substantial heterogeneity of purpose, scope, theoretical underpinning, processes considered, parameterizations, resolution (grain size), and spatial extent. This heterogeneity reflects the lack of a unified understanding of the marine ecosystem and implies that the assemblage of all models is more likely to include a greater number of relevant processes than any single model. The current Fish-MIP protocol is designed to allow these heterogeneous models to be forced with common Earth System Model (ESM) Coupled Model Intercomparison Project Phase 5 (CMIP5) outputs under prescribed scenarios for historic (from the 1950s) and future (to 2100) time periods; it will be adapted to CMIP phase 6 (CMIP6) in future iterations. It also describes a standardized set of outputs for each participating Fish-MIP model to produce. This enables the broad characterization of differences between and uncertainties within models and projections when assessing climate and fisheries impacts on marine ecosystems and the services they provide. The systematic generation, collation, and comparison of results from Fish-MIP will inform an understanding of the range of plausible changes in marine ecosystems and improve our capacity to define and convey the strengths and weaknesses of model-based advice on future states of marine ecosystems and fisheries. Ultimately, Fish-MIP represents a step towards bringing together the marine ecosystem modelling community to produce consistent ensemble medium- and long-term projections of marine ecosystems.
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