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- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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- Moon, S., et al.
(författare)
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Present-Day Stress Field Influences Bedrock Fracture Openness Deep Into the Subsurface
- 2020
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 47:23
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Tidskriftsartikel (refereegranskat)abstract
- Fracturing of bedrock promotes water-rock interactions and influences the formation of the life-sustaining layer of soil at Earth's surface. Models predict that present-day stress fields should influence bedrock fracture openness, but testing this prediction has proven difficult because comprehensive fracture data sets are rarely available. We model the three-dimensional present-day stress field beneath the deglaciated, low-relief landscape of Forsmark, Sweden. We account for ambient regional stresses, pore pressure, topography, sediment weight, and seawater loading. We then compare the modeled stresses to a data set of similar to 50,000 fractures reaching depths of 600 m at Forsmark. We show that modeled failure proxies correlate strongly with the fraction of observed open fractures to depths of similar to 500 m. This result implies that the present-day regional stress field, affected by surface conditions and pore pressure, influences fracture openness in bedrock hundreds of meters beneath the surface, thereby preparing the rock for further weathering. Plain Language Summary The "critical zone"-the life-sustaining part of the Earth that extends from the top of the tree canopy to the bottom of permeable bedrock-is essential for ecosystems and agriculture. The opening of bedrock fractures and onset of water-rock interaction are crucial to the formation of the critical zone. Within the bedrock, the intensities of horizontal regional forces and vertical gravitational forces typically increase with depth. These force intensities, or stresses, are modified by surface effects associated with topography, the weight of overlying seawater and sediment, and by groundwater pressure. However, the influence of these surface effects on fractures has been difficult to observe because comprehensive fracture data sets are rare. In this study, we examine whether, and to what depths, bedrock may fracture under the influence of stress associated with surficial conditions. We compare bedrock stress calculations with similar to 50,000 fractures from 18 cores reaching depths of 600 m at Forsmark, Sweden. We find that the present-day stress field influences the opening of fractures to depths of 500 m, contributing to the formation of the critical zone and the preparation of rock for weathering hundreds of meters beneath the surface, much deeper than previously thought.
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- Moon, Seulgi, et al.
(författare)
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Present-Day Stress Field Influences Bedrock Fracture Openness Deep Into the Subsurface
- 2020
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 47:23
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Tidskriftsartikel (refereegranskat)abstract
- Fracturing of bedrock promotes water-rock interactions and influences the formation of the life-sustaining layer of soil at Earth's surface. Models predict that present-day stress fields should influence bedrock fracture openness, but testing this prediction has proven difficult because comprehensive fracture data sets are rarely available. We model the three-dimensional present-day stress field beneath the deglaciated, low-relief landscape of Forsmark, Sweden. We account for ambient regional stresses, pore pressure, topography, sediment weight, and seawater loading. We then compare the modeled stresses to a data set of similar to 50,000 fractures reaching depths of 600 m at Forsmark. We show that modeled failure proxies correlate strongly with the fraction of observed open fractures to depths of similar to 500 m. This result implies that the present-day regional stress field, affected by surface conditions and pore pressure, influences fracture openness in bedrock hundreds of meters beneath the surface, thereby preparing the rock for further weathering. Plain Language Summary The "critical zone"-the life-sustaining part of the Earth that extends from the top of the tree canopy to the bottom of permeable bedrock-is essential for ecosystems and agriculture. The opening of bedrock fractures and onset of water-rock interaction are crucial to the formation of the critical zone. Within the bedrock, the intensities of horizontal regional forces and vertical gravitational forces typically increase with depth. These force intensities, or stresses, are modified by surface effects associated with topography, the weight of overlying seawater and sediment, and by groundwater pressure. However, the influence of these surface effects on fractures has been difficult to observe because comprehensive fracture data sets are rare. In this study, we examine whether, and to what depths, bedrock may fracture under the influence of stress associated with surficial conditions. We compare bedrock stress calculations with similar to 50,000 fractures from 18 cores reaching depths of 600 m at Forsmark, Sweden. We find that the present-day stress field influences the opening of fractures to depths of 500 m, contributing to the formation of the critical zone and the preparation of rock for weathering hundreds of meters beneath the surface, much deeper than previously thought.
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- Schmising, C. von Korff, et al.
(författare)
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Imaging Ultrafast Demagnetization Dynamics after a Spatially Localized Optical Excitation
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:21
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Tidskriftsartikel (refereegranskat)abstract
- Ultrashort, coherent x-ray pulses of a free-electron laser are used to holographically image the magnetization dynamics within a magnetic domain pattern after creation of a localized excitation via an optical standing wave. We observe a spatially confined reduction of the magnetization within a couple of hundred femtoseconds followed by its slower recovery. Additionally, the experimental results show evidence of a spatial evolution of magnetization, which we attribute to ultrafast transport of nonequilibrium spin-polarized electrons for early times and to a fluence-dependent remagnetization rate for later times.
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- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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