| 11. |
- 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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| 12. |
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| 13. |
- Li, Ping, et al.
(författare)
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Fructose sensitivity is suppressed in Arabidopsis by the transcription factor ANAC089 lacking the membrane-bound domain
- 2011
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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. ; 108:8, s. 3436-3441
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Tidskriftsartikel (refereegranskat)abstract
- In living organisms sugars not only provide energy and carbon skeletons but also act as evolutionarily conserved signaling molecules. The three major soluble sugars in plants are sucrose, glucose, and fructose. Information on plant glucose and sucrose signaling is available, but to date no fructose-specific signaling pathway has been reported. In this study, sugar repression of seedling development was used to study fructose sensitivity in the Landsberg erecta (Ler)/Cape Verde Islands (Cvi) recombinant inbred line population, and eight fructose-sensing quantitative trait loci (QTLs) (FSQ1-8) were mapped. Among them, FSQ6 was confirmed to be a fructose-specific QTL by analyzing near-isogenic lines in which Cvi genomic fragments were introgressed in the Ler background. These results indicate the existence of a fructose-specific signaling pathway in Arabidopsis. Further analysis demonstrated that the FSQ6-associated fructose-signaling pathway functions independently of the hexokinase1 (HXK1) glucose sensor. Remarkably, fructose-specific FSQ6 downstream signaling interacts with abscisic acid (ABA)- and ethylene-signaling pathways, similar to HXK1-dependent glucose signaling. The Cvi allele of FSQ6 acts as a suppressor of fructose signaling. The FSQ6 gene was identified using map-based cloning approach, and FSQ6 was shown to encode the transcription factor gene Arabidopsis NAC (petunia No apical meristem and Arabidopsis transcription activation factor 1, 2 and Cup-shaped cotyledon 2) domain containing protein 89 (ANAC089). The Cvi allele of FSQ6/ANAC089 is a gain-of-function allele caused by a premature stop in the third exon of the gene. The truncated Cvi FSQ6/ANAC089 protein lacks a membrane association domain that is present in ANAC089 proteins from other Arabidopsis accessions. As a result, Cvi FSQ6/ANAC089 is constitutively active as a transcription factor in the nucleus.
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| 14. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 15. |
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| 16. |
- Renoult, Martin, et al.
(författare)
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A Bayesian framework for emergent constraints : case studies of climate sensitivity with PMIP
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1715-1735
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we introduce a Bayesian framework, which is explicit about prior assumptions, for using model ensembles and observations together to constrain future climate change. The emergent constraint approach has seen broad application in recent years, including studies constraining the equilibrium climate sensitivity (ECS) using the Last Glacial Maximum (LGM) and the mid-Pliocene Warm Period (mPWP). Most of these studies were based on ordinary least squares (OLS) fits between a variable of the climate state, such as tropical temperature, and climate sensitivity. Using our Bayesian method, and considering the LGM and mPWP separately, we obtain values of ECS of 2.7K (0.6-5.2, 5th-95th percentiles) using the PMIP2, PMIP3, and PMIP4 datasets for the LGM and 2.3K (0.5-4.4) with the PlioMIP1 and PlioMIP2 datasets for the mPWP. Restricting the ensembles to include only the most recent version of each model, we obtain 2.7K (0.7-5.2) using the LGM and 2.3K (0.4-4.5) using the mPWP. An advantage of the Bayesian framework is that it is possible to combine the two periods assuming they are independent, whereby we obtain a tighter constraint of 2.5K (0.8-4.0) using the restricted ensemble. We have explored the sensitivity to our assumptions in the method, including considering structural uncertainty, and in the choice of models, and this leads to 95% probability of climate sensitivity mostly below 5K and only exceeding 6K in a single and most uncertain case assuming a large structural uncertainty. The approach is compared with other approaches based on OLS, a Kalman filter method, and an alternative Bayesian method. An interesting implication of this work is that OLS-based emergent constraints on ECS generate tighter uncertainty estimates, in particular at the lower end, an artefact due to a flatter regression line in the case of lack of correlation. Although some fundamental challenges related to the use of emergent constraints remain, this paper provides a step towards a better foundation for their potential use in future probabilistic estimations of climate sensitivity.
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| 17. |
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| 18. |
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| 19. |
- Shi, Hao, et al.
(författare)
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Corrosion behavior of Al-containing MAX-phase coatings exposed to oxygen containing molten Pb at 600 degrees C
- 2022
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Ingår i: Corrosion Science. - : Elsevier. - 0010-938X .- 1879-0496. ; 201
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Tidskriftsartikel (refereegranskat)abstract
- Four types of MAX-phase coating samples (Cr2AlC, V2AlC, Ti2AlC, and Ti3AlC2), synthesized via physical vapor deposition and post-annealing of elemental multilayer films, have been investigated toward their potential corrosion protection in 10(-6) wt% oxygen-containing molten Pb for 3200 h at 600 degrees C. Three MAX-phase coatings (Cr2AlC, Ti2AlC, and Ti3AlC2) are corrosion resistant against the molten Pb, via formation of a protective oxide layer. Specifically, various oxide scales formed on each sample: an Al2O3 scale, containing a low amount of Cr2O3 was formed in case of the Cr2AlC coating; a mixed Al2O3 and TiO2 oxide scale was observed for both Ti2AlC and Ti3AlC2 coatings. A more complex mixed oxide layer consisting of VO2, V4O7, and Pb-3(VO4)(2) phases is formed on the V2AlC coating, while the MAX-phase coating was almost entirely consumed. According to their corrosion performance against oxygen containing molten Pb, the order of corrosion resistance is: Cr2AlC > Ti2AlC > Ti3AlC2 > V2AlC.
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| 20. |
- Telloni, Daniele, et al.
(författare)
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Observation and Modeling of the Solar Wind Turbulence Evolution in the Sub-Mercury Inner Heliosphere
- 2022
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 938:2
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Tidskriftsartikel (refereegranskat)abstract
- This letter exploits the radial alignment between the Parker Solar Probe and BepiColombo in late 2022 February, when both spacecraft were within Mercury's orbit. This allows the study of the turbulent evolution, namely, the change in spectral and intermittency properties, of the same plasma parcel during its expansion from 0.11 to 0.33 au, a still unexplored region. The observational analysis of the solar wind turbulent features at the two different evolution stages is complemented by a theoretical description based on the turbulence transport model equations for nearly incompressible magnetohydrodynamics. The results provide strong evidence that the solar wind turbulence already undergoes significant evolution at distances less than 0.3 au from the Sun, which can be satisfactorily explained as due to evolving slab fluctuations. This work represents a step forward in understanding the processes that control the transition from weak to strong turbulence in the solar wind and in properly modeling the heliosphere.
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