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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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- Gu, Yeqing, et al.
(författare)
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Consumption of ultraprocessed food and development of chronic kidney disease : the Tianjin Chronic Low-Grade Systemic Inflammation and Health and UK Biobank Cohort Studies
- 2023
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 117:2, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany ultraprocessed food (UPF)-derived by-products may play a role in the development of chronic kidney disease (CKD). Although several studies have assessed the association of UPFs with kidney function decline or CKD in various countries, no evidence has been shown in China and the United Kingdom.ObjectivesThis study aims to evaluate the association between UPF consumption and risk of CKD in 2 large cohort studies from China and the United Kingdom.MethodsIn total, 23,775 and 102,332 participants without baseline CKD were enrolled in the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) and UK Biobank cohort studies, respectively. Information on UPF consumption was obtained from a validated food frequency questionnaire in the TCLSIH and 24-h dietary recalls in the UK Biobank cohort. CKD was defined as an estimated glomerular filtration rate of ResultsAfter a median follow-up of 4.0 and 10.1 y, the incidence rates of CKD were around 1.1% and 1.7% in the TCLSIH and UK Biobank cohorts, respectively. The multivariable hazard ratio [95% confidence interval] of CKD across increasing quartiles (quartiles 1–4) of UPF consumption were 1 (reference), 1.24 (0.89, 1.72), 1.30 (0.91, 1.87), and 1.58 (1.07, 2.34) (P for trend = 0.02) in the TCLSIH cohort and 1 (reference), 1.14 (1.00, 1.31), 1.16 (1.01, 1.33), and 1.25 (1.09, 1.43) (P for trend < 0.01) in the UK Biobank cohort, respectively.ConclusionsOur finding indicated that higher UPF consumption is associated with a higher risk of CKD. Moreover, restricting UPF consumption may potentially benefit the prevention of CKD. Further clinical trials are required to clarify the causality.
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- Calabrese, Claudia, et al.
(författare)
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Genomic basis for RNA alterations in cancer
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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- Han, Zixuan, et al.
(författare)
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The changes in ENSO-induced tropical Pacific precipitation variability in the past warm and cold climates from the EC-Earth simulations
- 2020
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 55, s. 503-519
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Tidskriftsartikel (refereegranskat)abstract
- The El Nino-Southern Oscillation (ENSO) is one of the most significant climate variability signals. Studying the changes in ENSO-induced precipitation variability (ENSO precipitation) in the past climate offers a possibility to a better understanding of how they may change under future climate conditions. This study uses simulations performed with the European community Earth-System Model (EC-Earth) to investigate the relative contributions of dynamic effect (the circulation anomalies together with the climatological specific humidity) and thermodynamic effect (the specific humidity anomalies together with the climatological circulation) on the changes in ENSO precipitation in the past warm and cold climates, represented by the Pliocene and the Last Glacial Maximum (LGM), respectively. The results show that the changes in ENSO precipitation are intensified (weakened) over the tropical western Pacific but weakened (intensified) over the tropical central Pacific in Pliocene (LGM) compared with the pre-industrial (PI) simulation. Based on the decomposed moisture budget equation, these changes in ENSO precipitation patterns are highly related to the dynamic effect. The mechanism can be understood as follows: the zonal gradient of the mean sea surface temperature (SST) over the tropical Indo-Pacific is increased (reduced) during the Pliocene (LGM), leading to the strengthening (weakening) of Pacific Walker Circulation as well as a westward (eastward) shift. In the Pliocene, the westward shift of Walker Circulation results in an increased (decreased) ENSO-induced low-level vertical velocity variability in the tropical western Pacific (central Pacific), and, in turn, favoring convergent (divergent) moisture transport through a dynamic process, and then causing intensified (weakened) ENSO precipitation there. The opposite mechanism exists in LGM. These results suggest that changes in the zonal SST gradient over tropical Indo-Pacific under different climate conditions determine the changes in ENSO precipitation through a dynamic process.
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- Zhang, Qiong, et al.
(författare)
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Simulating the mid-Holocene, last interglacial and mid-Pliocene climate with EC-Earth3-LR
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:2, s. 1147-1169
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Tidskriftsartikel (refereegranskat)abstract
- As global warming is proceeding due to rising greenhouse gas concentrations, the Earth system moves towards climate states that challenge adaptation. Past Earth system states are offering possible modelling systems for the global warming of the coming decades. These include the climate of the mid-Pliocene (similar to 3 Ma), the last interglacial (similar to 129-116 ka) and the mid-Holocene (similar to 6 ka). The simulations for these past warm periods are the key experiments in the Paleoclimate Model Intercomparison Project (PMIP) phase 4, contributing to phase 6 of the Coupled Model Intercomparison Project (CMIP6). Paleoclimate modelling has long been regarded as a robust out-of-sample test bed of the climate models used to project future climate changes. Here, we document the model setup for PMIP4 experiments with EC-Earth3-LR and present the large-scale features from the simulations for the mid-Holocene, the last interglacial and the mid-Pliocene. Using the pre-industrial climate as a reference state, we show global temperature changes, large-scale Hadley circulation and Walker circulation, polar warming, global monsoons and the climate variability modes - El Nino-Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO). EC-Earth3-LR simulates reasonable climate responses during past warm periods, as shown in the other PMIP4-CMIP6 model ensemble. The systematic comparison of these climate changes in past three warm periods in an individual model demonstrates the model's ability to capture the climate response under different climate forcings, providing potential implications for confidence in future projections with the EC-Earth model.
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| 9. |
- Lu, Zhengyao, et al.
(författare)
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Impacts of Large-Scale Sahara Solar Farms on Global Climate and Vegetation Cover
- 2021
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 48:2
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale photovoltaic solar farms envisioned over the Sahara desert can meet the world's energy demand while increasing regional rainfall and vegetation cover. However, adverse remote effects resulting from atmospheric teleconnections could offset such regional benefits. We use state-of-the-art Earth-system model simulations to evaluate the global impacts of Sahara solar farms. Our results indicate a redistribution of precipitation causing Amazon droughts and forest degradation, and global surface temperature rise and sea-ice loss, particularly over the Arctic due to increased polarward heat transport, and northward expansion of deciduous forests in the Northern Hemisphere. We also identify reduced El Niño-Southern Oscillation and Atlantic Niño variability and enhanced tropical cyclone activity. Comparison to proxy inferences for a wetter and greener Sahara ∼6,000 years ago appears to substantiate these results. Understanding these responses within the Earth system provides insights into the site selection concerning any massive deployment of solar energy in the world's deserts.
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| 10. |
- Xu, Jun, et al.
(författare)
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Preservation effects on stable isotope ratios and consequences for the reconstruction of energetic pathways
- 2011
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Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 45:4, s. 483-492
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Tidskriftsartikel (refereegranskat)abstract
- Stable isotope analysis provides a powerful tool for describing the energetic pathways in a variety of ecosystems. However, isotope ratios of animal tissues can be altered by preservation methods, potentially leading to biased estimates of energy pathways when they are not taken into account. Here, we investigated the direct preservation effects of formalin, ethanol, NaCl, and drying on the delta C-13 and delta N-15 of fish muscle tissues, as well as the ultimate effects on the reconstruction of the energy pathways. All preservation methods, except drying, had significant impacts on delta C-13 and delta N-15 values. The effects of preservation appear to be highly taxa-specific and no significant time-dependent variations in nearly 2-year duration of preservation. delta C-13 and delta N-15 values were generally changed dramatically within the early stage of the preservation process and became stable over a relatively long-term preservation. Using an isotopic balance mixing model, the isotope-based food web reconstruction reveals that, without preservation correction, the importance of the pelagic energetic pathways for the fishes could be misestimated, except for the drying preservation. These results highlight that preservation can bias the interpretation of food web reconstruction results.
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