| 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. |
- Brierley, Chris M., et al.
(författare)
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Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1847-1872
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Tidskriftsartikel (refereegranskat)abstract
- The mid-Holocene (6000 years ago) is a standard time period for the evaluation of the simulated response of global climate models using palaeoclimate reconstructions. The latest mid-Holocene simulations are a palaeoclimate entry card for the Palaeoclimate Model Intercomparison Project (PMIP4) component of the current phase of the Coupled Model Intercomparison Project (CMIP6) - hereafter referred to as PMIP4-CMIP6. Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the Northern Hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2K cooler than the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe, and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on the hydrological cycle, feedback strength, and potentially climate sensitivity.
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| 3. |
- Brown, Josephine R., et al.
(författare)
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Comparison of past and future simulations of ENSO in CMIP5/PMIP3 and CMIP6/PMIP4 models
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1777-1805
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Tidskriftsartikel (refereegranskat)abstract
- El Niño–Southern Oscillation (ENSO) is the strongest mode of interannual climate variability in the current climate, influencing ecosystems, agriculture, and weather systems across the globe, but future projections of ENSO frequency and amplitude remain highly uncertain. A comparison of changes in ENSO in a range of past and future climate simulations can provide insights into the sensitivity of ENSO to changes in the mean state, including changes in the seasonality of incoming solar radiation, global average temperatures, and spatial patterns of sea surface temperatures. As a comprehensive set of coupled model simulations is now available for both palaeoclimate time slices (the Last Glacial Maximum, mid-Holocene, and last interglacial) and idealised future warming scenarios (1 % per year CO2 increase, abrupt four-time CO2 increase), this allows a detailed evaluation of ENSO changes in this wide range of climates. Such a comparison can assist in constraining uncertainty in future projections, providing insights into model agreement and the sensitivity of ENSO to a range of factors. The majority of models simulate a consistent weakening of ENSO activity in the last interglacial and mid-Holocene experiments, and there is an ensemble mean reduction of variability in the western equatorial Pacific in the Last Glacial Maximum experiments. Changes in global temperature produce a weaker precipitation response to ENSO in the cold Last Glacial Maximum experiments and an enhanced precipitation response to ENSO in the warm increased CO2 experiments. No consistent relationship between changes in ENSO amplitude and annual cycle was identified across experiments.
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| 4. |
- Gravgaard Askjær, Thomas, et al.
(författare)
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Multi-centennial Holocene climate variability in proxy records and transient model simulations
- 2022
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 296
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Tidskriftsartikel (refereegranskat)abstract
- Variability on centennial to multi-centennial timescales is mentioned as a feature in reconstructions of the Holocene climate. As more long transient model simulations with complex climate models become available and efforts have been made to compile large proxy databases, there is now a unique opportunity to study multi-centennial variability with greater detail and a large amount of data than earlier. This paper presents a spectral analysis of transient Holocene simulations from 9 models and 120 proxy records to find the common signals related to oscillation periods and geographic dependencies and discuss the implications for the potential driving mechanisms. Multi-centennial variability is significant in most proxy records, with the dominant oscillation periods around 120–130 years and an average of 240 years. Spectra of model-based global mean temperature (GMT) agree well with proxy evidence with significant multi-centennial variability in all simulations with the dominant oscillation periods around 120–150 years. It indicates a comparatively good agreement between model and proxy data. A lack of latitudinal dependencies in terms of oscillation period is found in both the model and proxy data. However, all model simulations have the highest spectral density distributed over the Northern hemisphere high latitudes, which could indicate a particular variability sensitivity or potential driving mechanisms in this region. Five models also have differentiated forcings simulations with various combinations of forcing agents. Significant multi-centennial variability with oscillation periods between 100 and 200 years is found in all forcing scenarios, including those with only orbital forcing. The different forcings induce some variability in the system. Yet, none appear to be the predominant driver based on the spectral analysis. Solar irradiance has long been hypothesized to be a primary driver of multi-centennial variability. However, all the simulations without this forcing have shown significant multi-centennial variability. The results then indicate that internal mechanisms operate on multi-centennial timescales, and the North Atlantic-Arctic is a region of interest for this aspect.
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| 5. |
- Hou, Qiong, et al.
(författare)
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A triphenylamine-based four-armed molecule for solution-processed organic solar cells with high photo-voltage
- 2013
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Ingår i: JOURNAL OF MATERIALS CHEMISTRY A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 1:16, s. 4937-4940
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Tidskriftsartikel (refereegranskat)abstract
- A new four-armed molecule Th-4(DTPAB) with a triphenylamine-benzothiadiazole-triphenylamine unit as the core and 4-hexylthiophene as arms was synthesized. Solution-processed organic solar cells based on blends of Th-4(DTPAB) and PC71BM demonstrate a power conversion efficiency of 3.18% with a high open circuit voltage of 0.96 V.
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| 6. |
- Kageyama, Masa, et al.
(författare)
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A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka : sea ice data compilation and model differences
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 37-62
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Tidskriftsartikel (refereegranskat)abstract
- The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations.
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| 7. |
- Kageyama, Masa, et al.
(författare)
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The PMIP4 contribution to CMIP6-Part 4 : Scientific objectives and experimental design of the PMIP4-CMIP6 Last Glacial Maximum experiments and PMIP4 sensitivity experiments
- 2017
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:11, s. 4035-4055
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Tidskriftsartikel (refereegranskat)abstract
- The Last Glacial Maximum (LGM, 21 000 years ago) is one of the suite of paleoclimate simulations included in the current phase of the Coupled Model Intercomparison Project (CMIP6). It is an interval when insolation was similar to the present, but global ice volume was at a maximum, eustatic sea level was at or close to a minimum, greenhouse gas concentrations were lower, atmospheric aerosol loadings were higher than today, and vegetation and land-surface characteristics were different from today. The LGM has been a focus for the Paleoclimate Modelling Intercomparison Project (PMIP) since its inception, and thus many of the problems that might be associated with simulating such a radically different climate are well documented. The LGM state provides an ideal case study for evaluating climate model performance because the changes in forcing and temperature between the LGM and pre-industrial are of the same order of magnitude as those projected for the end of the 21st century. Thus, the CMIP6 LGM experiment could provide additional information that can be used to constrain estimates of climate sensitivity. The design of the Tier 1 LGM experiment (lgm) includes an assessment of uncertainties in boundary conditions, in particular through the use of different reconstructions of the ice sheets and of the change in dust forcing. Additional (Tier 2) sensitivity experiments have been designed to quantify feedbacks associated with land-surface changes and aerosol loadings, and to isolate the role of individual forcings. Model analysis and evaluation will capitalize on the relative abundance of paleoenvironmental observations and quantitative climate reconstructions already available for the LGM.
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| 8. |
- Kang, Nai-xin, et al.
(författare)
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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses
- 2022
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Ingår i: Acta Pharmacologica Sinica. - : Springer Nature. - 1671-4083 .- 1745-7254. ; 43, s. 977-991
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Tidskriftsartikel (refereegranskat)abstract
- Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 mu M) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 +/- 0.05 mu M against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-beta response, since knockdown of IFN-beta abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg center dot kg(-1) center dot d(-1), i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-gamma, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-beta by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.
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| 9. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 10. |
- Lamichhaney, Sangeet, 1984-, et al.
(författare)
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Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax)
- 2016
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 48:1, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- The ruff is a Palearctic wader with a spectacular lekking behavior where highly ornamented males compete for females1,2,3,4. This bird has one of the most remarkable mating systems in the animal kingdom, comprising three different male morphs (independents, satellites and faeders) that differ in behavior, plumage color and body size. Remarkably, the satellite and faeder morphs are controlled by dominant alleles5,6. Here we have used whole-genome sequencing and resolved the enigma of how such complex phenotypic differences can have a simple genetic basis. The Satellite and Faeder alleles are both associated with a 4.5-Mb inversion that occurred about 3.8 million years ago. We propose an evolutionary scenario where the Satellite chromosome arose by a rare recombination event about 500,000 years ago. The ruff mating system is the result of an evolutionary process in which multiple genetic changes contributing to phenotypic differences between morphs have accumulated within the inverted region.
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