| 311. |
- Ugalde-Morales, Emilio, et al.
(författare)
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Interval breast cancer is associated with interferon immune response
- 2022
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 162, s. 194-205
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aggressive nature of breast cancers detected between planned mammographic screens, so-called interval cancers, remains elusive. Here, we aim to characterise underlying molecular features of interval cancer. Methods: From 672 patients with invasive breast cancer, we analysed gene expression differences between 90 ‘true’ interval cancer cases (i.e. women with low-dense breasts defined as per cent mammographic density <25%) and 310 screen-detected tumours while accounting for PAM50 subtypes and thus overall tumour aggressiveness. We computed an interval cancer gene expression profile (IC-Gx) in a total of 2270 breast tumours (regardless of interval cancer status) and tested for association with expression-based immune subtypes in breast cancer. In addition, we investigated the contribution of inherited and somatic genetic variants in distinct features of interval cancer. Results: We identified 8331 genes nominally associated with interval cancer (P-value < 0.05, fold-change > 1.5). Gene set enrichment analysis showed immune-related pathways as key processes altered in interval cancer. Our IC-Gx, based on 47 genes with the strongest associations (false discovery rate < 0.05), was found to be associated mainly with immune subtypes involving interferon response. We isolated an interaction network of interval cancer and interferon genes for which a significant load of somatic and germline variants in class I interferon genes was observed. Conclusion: We identified novel molecular features of interval breast cancer highlighting interferon pathways as a potential target for prevention or treatment.
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| 312. |
- van de Velde, Sebastiaan, et al.
(författare)
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Elevated sedimentary removal of Fe, Mn, and trace elements following a transient oxygenation event in the Eastern Gotland Basin, central Baltic Sea
- 2020
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 271, s. 16-32
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Tidskriftsartikel (refereegranskat)abstract
- Iron, manganese, and trace elements play an important role in the marine carbon cycle as they are limiting nutrients for marine primary productivity. Water column concentrations of these bio-essential elements are controlled by the balance between input and removal, with burial in marine sediments being the main sink. The efficiency of this burial sink is dependent on the redox state of the water column, with sediments underlying a sulphidic (euxinic) water column being the most efficient sinks for Fe, but also Mn and trace elements (Co, Cd, Ni, Mo, As, W, V, and U). Transient changes in ocean redox state can hence affect trace element burial, and correspondingly, the ocean’s trace element inventory, but the impact of transient oxygenation events on trace element cycling is currently not well understood. Here, we investigate the impact of a natural oxygenation event on trace element release and burial in sediments of the Eastern Gotland Basin (EGB), a sub-basin of the Baltic Sea. After being anoxic (< 0.5 µM O2) for ∼10 years, the deep waters of the EGB experienced a natural oxygenation event (Major Baltic Inflow, MBI) in 2015. Following this oxygenation event, we deployed benthic chamber landers along a depth transect in the EGB in April 2016, 2017 and 2018. We complemented these in situ flux measurements with analyses of water column, solid phase and pore water chemistry. Overall, the event increased the benthic effluxes of dissolved trace elements, though particular responses were element-specific and were caused by different mechanisms. Enhanced fluxes of Cd and U were caused by oxidative remobilisation, while Ni showed little response to the inflow of oxygen. In contrast, enhanced release of Co, Mo, As, W, and V was caused by the enhanced transient input of Mn oxides into the sediment, whereas Fe oxides were of minor importance. Following the dissolution of the oxides in the sediment, Mn and W were nearly completely recycled back to the water column, while fractions of Fe, Co, Mo, As, and V were retained in the sediment. Our results suggest that transient oxygenation events in euxinic basins may decrease the water column inventory of certain trace elements (Fe, Co, Mo, As, and V), thus potentially affecting global marine primary productivity on longer timescales.
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| 313. |
- van de Velde, Sebastian J, et al.
(författare)
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Exceptionally high respiration rates in the reactive surface layer of sediments underlying oxygen-deficient bottom waters
- 2023
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Ingår i: Proceedings of the Royal Society. Mathematical, Physical and Engineering Sciences. - : ROYAL SOC. - 1364-5021 .- 1471-2946. ; 479:2275
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Tidskriftsartikel (refereegranskat)abstract
- Organic carbon (OC) burial efficiency, which relates the OC burial rate to respiration in the seafloor, is a critical parameter in the reconstruction of past marine primary productivities. The current accepted theory is that sediments underlying oxygen-deficient (anoxic) bottom waters have low respiration rates and high OC burial efficiencies. By combining novel in situ measurements in anoxic basins with reaction-transport modelling, we demonstrate that sediments underlying anoxic bottom waters have much higher respiration rates than commonly assumed. A major proportion of the carbon respiration is concentrated in the top millimeter—the so-called ‘reactive surface layer’—which is likely a feature in approximately 15% of the coastal seafloor. When re-evaluating previously published data in light of our results, we conclude that the impact of bottom-water anoxia on OC burial efficiencies in marine sediments is small. Consequently, reconstructions of past marine primary productivity in a predominantly anoxic ocean based on OC burial rates might be underestimated by up to an order of magnitude.
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| 314. |
- Viktorsson, Lena, 1980, et al.
(författare)
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Benthic phosphorus dynamics in the Gulf of Finland, Baltic Sea
- 2012
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Ingår i: Aquatic geochemistry. - : Springer Science and Business Media LLC. - 1380-6165 .- 1573-1421. ; 18, s. 543-564
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Tidskriftsartikel (refereegranskat)abstract
- Benthic fluxes of soluble reactive phosphorus (SRP) and dissolved inorganic carbon (DIC) were measured in situ using autonomous landers in the Gulf of Finland in the Baltic Sea, on four expeditions between 2002 and 2005. These measurements together with model estimates of bottom water oxygen conditions were used to compute the magnitude of the yearly integrated benthic SRP flux (also called internal phosphorus load). The yearly integrated benthic SRP flux was found to be almost 10 times larger than the external (river and land sources) phosphorus load. The average SRP flux was 1.25 ± 0.56 mmol m-2 d-1 on anoxic bottoms, and -0.01 ± 0.08 mmol m-2 d-1 on oxic bottoms. The bottom water oxygen conditions determined whether the SRP flux was in a high or low regime, and degradation of organic matter (as estimated from benthic DIC fluxes) correlated positively with SRP fluxes on anoxic bottoms. From this correlation, we estimated a potential increase in phosphorus flux of 0.69 ± 0.26 mmol m-2 d-1 from presently oxic bottoms, if they would turn anoxic. An almost full annual data set of in situ bottom water oxygen measurements showed high variability of oxygen concentration. Because of this, an estimate of the time which the sediments were exposed to oxygenated overlying bottom water was computed using a coupled thermohydrodynamic ocean–sea and ecosystem model. Total phosphorus burial rates were calculated from vertical profiles of total phosphorus in sediment and sediment accumulation rates. Recycling and burial efficiencies for phosphorus of 97 and 3%, respectively, were estimated for anoxic accumulation bottoms from a benthic mass balance, which was based on the measured effluxes and burial rates.
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| 315. |
- Viktorsson, Lena, 1980, et al.
(författare)
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Phosphorus recycling in sediments of the central Baltic Sea
- 2013
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 10, s. 3901-3916
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Tidskriftsartikel (refereegranskat)abstract
- Benthic fluxes of phosphorus (P) were measured in situ in the Eastern Gotland Basin (EGB), central Baltic Sea, using benthic landers. A total of 40 flux measurements of dissolved inorganic P (DIP) on 13 stations at water depths ranging 30–210 m and under different oxygen regimes were carried out on three cruises during three consecutive years (2008–2010) in August–September. Our study is the first to report in situ DIP fluxes in the Baltic proper, and it provides the most comprehensive dataset of benthic fluxes of DIP and dissolved organic P (DOP) in the Baltic proper existing to date. DIP fluxes increased with increasing water depth and with decreasing bottom water oxygen concentration. Average DIP fluxes were calculated for oxic bottom water conditions (−0.003±0.040 mmol m−2 d−1), hypoxic conditions (0.027±0.067 mmol m−2 d−1) and anoxic conditions (0.376±0.214 mmol m−2 d−1). The mean DIP flux at anoxic bottoms was higher than previous estimates based on ex situ measurements of pore water gradients. The DIP flux was positively correlated with the organic carbon inventory of sediment, and the benthic flux of dissolved inorganic carbon (DIC) at anoxic stations, but these variables were uncorrelated at oxic stations. The positive correlation between DIP and DIC fluxes suggests that the benthic DIP efflux from anoxic bottoms in the Baltic Proper is mainly controlled by rates of deposition and degradation of organic matter. The flux from anoxic sediment was very P rich in relation to both C and nitrogen (N). The average C : P ratio in fluxes at anoxic accumulation bottoms was 69±15, which is well below the Redfield C : P ratio of 106 : 1. At oxic stations, however, the C : P flux ratio was much higher than the Redfield ratio, consistent with well-known P retention mechanisms associated with iron and bacteria in oxidised sediment. Using a benthic mass balance approach, a burial efficiency estimate of 0.2–12% was calculated for the anoxic part of the EGB, which suggests that anoxic Baltic sediments are very efficient in recycling deposited P. Based on the measured fluxes and the average areal extent of anoxic bottoms during years 1999–2006, an internal DIP load of 152 kton yr−1 was calculated. This is almost 9 times higher than the average external total phosphorus (TP) supply to the Baltic proper during the same period. This comparison clearly highlights the dominance of internally regenerated P as a DIP source in the Baltic Sea.
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| 316. |
- Visch, Wouter, et al.
(författare)
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Environmental impact of kelp (Saccharina latissima) aquaculture
- 2020
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X .- 1879-3363. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors The aim of the study was to assess the effect of seaweed cultivation on the coastal environment. We analysed a multitude of environmental parameters using an asymmetrical before after control impact (BACI) design, comparing the seaweed farm (impact) with multiple unaffected locations (controls). The seaweed farm had a significant positive effect on benthic infauna (p < 0.05) and was found to attract 17 mobile faunal and 7 other seaweed species, indicating that the farmed crop may provide habitat to mobile faunal species. A light attenuation of approximately 40% at 5 m depth was noted at the peak of the seaweed biomass just before harvest. No changes were observed in benthic oxygen flux, dissolved nutrient concentrations, and benthic mobile fauna between farm and control sites. These results show that seaweed aquaculture has limited environmental effects, especially compared to other forms of aquaculture such as fish and bivalve farming.
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| 317. |
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| 318. |
- Wang, Xiaoliang, et al.
(författare)
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Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 x 10(-8) as genome-wide significant, and p-values < 1 x 10(-5) as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 10(-8)) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.
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| 319. |
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| 320. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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