| 1. |
|
|
| 2. |
- Teumer, A, et al.
(author)
-
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
-
Journal article (peer-reviewed)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Wuttke, Matthias, et al.
(author)
-
A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
-
In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
-
Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
|
|
| 7. |
|
|
| 8. |
- Steffen, A., et al.
(author)
-
A synthesis of atmospheric mercury depletion event chemistry in the atmosphere and snow
- 2008
-
In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:6, s. 1445-1482
-
Journal article (peer-reviewed)abstract
- It was discovered in 1995 that, during the spring time, unexpectedly low concentrations of gaseous elemental mercury (GEM) occurred in the Arctic air. This was surprising for a pollutant known to have a long residence time in the atmosphere; however conditions appeared to exist in the Arctic that promoted this depletion of mercury (Hg). This phenomenon is termed atmospheric mercury depletion events (AMDEs) and its discovery has revolutionized our understanding of the cycling of Hg in Polar Regions while stimulating a significant amount of research to understand its impact to this fragile ecosystem. Shortly after the discovery was made in Canada, AMDEs were confirmed to occur throughout the Arctic, sub-Artic and Antarctic coasts. It is now known that, through a series of photochemically initiated reactions involving halogens, GEM is converted to a more reactive species and is subsequently associated to particles in the air and/or deposited to the polar environment. AMDEs are a means by which Hg is transferred from the atmosphere to the environment that was previously unknown. In this article we review Hg research taken place in Polar Regions pertaining to AMDEs, the methods used to collect Hg in different environmental media, research results of the current understanding of AMDEs from field, laboratory and modeling work, how Hg cycles around the environment after AMDEs, gaps in our current knowledge and the future impacts that AMDEs may have on polar environments. The research presented has shown that while considerable improvements in methodology to measure Hg have been made but the main limitation remains knowing the speciation of Hg in the various media. The processes that drive AMDEs and how they occur are discussed. As well, the role that the snow pack and the sea ice play in the cycling of Hg is presented. It has been found that deposition of Hg from AMDEs occurs at marine coasts and not far inland and that a fraction of the deposited Hg does not remain in the same form in the snow. Kinetic studies undertaken have demonstrated that bromine is the major oxidant depleting Hg in the atmosphere. Modeling results demonstrate that there is a significant deposition of Hg to Polar Regions as a result of AMDEs. Models have also shown that Hg is readily transported to the Arctic from source regions, at times during springtime when this environment is actively transforming Hg from the atmosphere to the snow and ice surfaces. The presence of significant amounts of methyl Hg in snow in the Arctic surrounding AMDEs is important because this species is the link between the environment and impacts to wildlife and humans. Further, much work on methylation and demethylation processes has occurred but these processes are not yet fully understood. Recent changes in the climate and sea ice cover in Polar Regions are likely to have strong effects on the cycling of Hg in this environment; however more research is needed to understand Hg processes in order to formulate meaningful predictions of these changes.
|
|
| 9. |
|
|
| 10. |
- Crippa, M., et al.
(author)
-
Organic aerosol components derived from 25 AMS data sets across Europe using a consistent ME-2 based source apportionment approach
- 2014
-
In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 14:12, s. 6159-6176
-
Journal article (peer-reviewed)abstract
- Organic aerosols (OA) represent one of the major constituents of submicron particulate matter (PM1) and comprise a huge variety of compounds emitted by different sources. Three intensive measurement field campaigns to investigate the aerosol chemical composition all over Europe were carried out within the framework of the European Integrated Project on Aerosol Cloud Climate and Air Quality Interactions (EUCAARI) and the intensive campaigns of European Monitoring and Evaluation Programme (EMEP) during 2008 (May-June and September-October) and 2009 (February-March). In this paper we focus on the identification of the main organic aerosol sources and we define a standardized methodology to perform source apportionment using positive matrix factorization (PMF) with the multilinear engine (ME-2) on Aerodyne aerosol mass spectrometer (AMS) data. Our source apportionment procedure is tested and applied on 25 data sets accounting for two urban, several rural and remote and two high altitude sites; therefore it is likely suitable for the treatment of AMS-related ambient data sets. For most of the sites, four organic components are retrieved, improving significantly previous source apportionment results where only a separation in primary and secondary OA sources was possible. Generally, our solutions include two primary OA sources, i.e. hydrocarbon-like OA (HOA) and biomass burning OA (BBOA) and two secondary OA components, i.e. semi-volatile oxygenated OA (SV-OOA) and low-volatility oxygenated OA (LV-OOA). For specific sites cooking-related (COA) and marine-related sources (MSA) are also separated. Finally, our work provides a large overview of organic aerosol sources in Europe and an interesting set of highly time resolved data for modeling purposes.
|
|
| 11. |
- Dall'Osto, M., et al.
(author)
-
Novel insights on new particle formation derived from a pan-european observing system
- 2018
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- The formation of new atmospheric particles involves an initial step forming stable clusters less than a nanometre in size (similar to 10 nm). Although at times, the same species can be responsible for both processes, it is thought that more generally each step comprises differing chemical contributors. Here, we present a novel analysis of measurements from a unique multi-station ground-based observing system which reveals new insights into continental-scale patterns associated with new particle formation. Statistical cluster analysis of this unique 2-year multi-station dataset comprising size distribution and chemical composition reveals that across Europe, there are different major seasonal trends depending on geographical location, concomitant with diversity in nucleating species while it seems that the growth phase is dominated by organic aerosol formation. The diversity and seasonality of these events requires an advanced observing system to elucidate the key processes and species driving particle formation, along with detecting continental scale changes in aerosol formation into the future.
|
|
| 12. |
- De Cicco, D., et al.
(author)
-
Optically variable AGN in the three-year VST survey of the COSMOS field
- 2019
-
In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 627
-
Journal article (peer-reviewed)abstract
- Context. The analysis of the variability of active galactic nuclei (AGN) at different wavelengths and the study of possible correlations of different spectral windows are a current main field of inquiry. Optical variability has been largely used to identify AGN in multivisit surveys. The strength of a selection based on optical variability lies in the opportunity of analyzing data from surveys of large sky areas by ground-based telescopes. However, the effectiveness of optical variability selection with respect to other multiwavelength techniques has been poorly studied down to the depth that is expected from next-generation surveys. Aims. Here we present the results of our r-band analysis of a sample of 299 optically variable AGN candidates in the VST survey of the COSMOS field, counting 54 visits spread over three observing seasons spanning more than three years. This dataset is more than three times larger than the dataset presented in our previous analysis, and the observing baseline is about eight times longer. Methods. We push toward deeper magnitudes (r(AB) similar to 23.5 mag) than were reached in past studies. We made wide use of ancillary multiwavelength catalogs in order to confirm the nature of our AGN candidates, and constrained the accuracy of the method based on spectroscopic and photometric diagnostics. We also performed tests aimed at assessing the relevance of dense sampling in view of future wide-field surveys. Results. We demonstrate that the method allows the selection of high-purity (> 86%) samples. We take advantage of the longer observing baseline to achieve great improvement in the completeness of our sample with respect to X-ray and spectroscopically confirmed samples of AGN (59% vs. similar to 15% in our previous work), as well as in the completeness of unobscured and obscured AGN. The effectiveness of the method confirms the importance of developing future more refined techniques for the automated analysis of larger datasets.
|
|
| 13. |
- Falchi, M., et al.
(author)
-
Low copy number of the salivary amylase gene predisposes to obesity
- 2014
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:5, s. 492-497
-
Journal article (peer-reviewed)abstract
- Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10-14) and serum enzyme levels (P < 2.20 × 10-16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy =-0.15 (0.02) kg/m 2; P = 6.93 × 10-10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10-10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. © 2014 Nature America, Inc. All rights reserved.
|
|
| 14. |
- Fountoukis, C., et al.
(author)
-
Organic aerosol concentration and composition over Europe: insights from comparison of regional model predictions with aerosol mass spectrometer factor analysis
- 2014
-
In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 14:17, s. 9061-9076
-
Journal article (peer-reviewed)abstract
- A detailed three-dimensional regional chemical transport model (Particulate Matter Comprehensive Air Quality Model with Extensions, PMCAMx) was applied over Europe, focusing on the formation and chemical transformation of organic matter. Three periods representative of different seasons were simulated, corresponding to intensive field campaigns. An extensive set of AMS measurements was used to evaluate the model and, using factor-analysis results, gain more insight into the sources and transformations of organic aerosol (OA). Overall, the agreement be-tween predictions and measurements for OA concentration is encouraging, with the model reproducing two-thirds of the data (daily average mass concentrations) within a factor of 2. Oxygenated OA (OOA) is predicted to contribute 93% to total OA during May, 87% during winter and 96% during autumn, with the rest consisting of fresh primary OA (POA). Predicted OOA concentrations compare well with the observed OOA values for all periods, with an average fractional error of 0.53 and a bias equal to -0.07 (mean error = 0.9 mu g m(-3), mean bias =-0.2 mu g m(-3)). The model systematically underpredicts fresh POA at most sites during late spring and autumn (mean bias up to -0.8 mu g m(-3)). Based on results from a source apportionment algorithm running in parallel with PMCAMx, most of the POA originates from biomass burning (fires and residential wood combustion), and therefore biomass burning OA is most likely underestimated in the emission inventory. The sensitivity of POA predictions to the corresponding emissions' volatility distribution is discussed. The model performs well at all sites when the Positive Matrix Factorization (PMF)-estimated low-volatility OOA is compared against the OA with saturation concentrations of the OA surrogate species C* <= 0.1 mu g m(-3) and semivolatile OOA against the OA with C* > 0.1 mu g m(-3).
|
|
| 15. |
- Halfvarson, Jonas, 1970-, et al.
(author)
-
Anti-Saccharomyces cerevisiae antibodies in twins with inflammatory bowel disease
- 2005
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 54:9, s. 1237-1243
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: An increased occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) is reported in unaffected members of families with Crohn's disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population.PATIENTS AND METHODS: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype.RESULTS: ASCA were more common in Crohn's disease than in ulcerative colitis (40/70 (57%) twins v 5/43 (12%) twins). Associations with ileal Crohn's disease, stricturing/penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn's disease compared with 7/27 (26%) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn's disease, in monozygotic (ICC = -0.02) or dizygotic (ICC = -0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn's disease (ICC = 0.76).CONCLUSIONS: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn's disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn's disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Nidens, N., et al.
(author)
-
Associations of prenatal exposure to phthalates and one phthalate substitute with anthropometric measures in early life : Results from the German LIFE Child cohort study
- 2021
-
In: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Bailliere Tindall Ltd. - 1521-690X .- 1532-1908. ; 35:5
-
Journal article (peer-reviewed)abstract
- Exposure to phthalates is widespread and especially early life stages represent a critical window of exposure. In the present study, we investigated the effect of prenatal exposure to phthalates on birth outcomes and weight development in early life. In 130 mother–child pairs, we estimated the association of concentrations of 13 phthalates in spot-urine samples collected during pregnancy and birth outcomes and weight gain in the first two years of life using robust linear regression. High molecular weight phthalates were inversely associated with birth weight in girls but not in boys. Thus, prenatal exposure to phthalates may affect birth weight in a sex-specific manner.
|
|
| 19. |
- Poulain, M., et al.
(author)
-
Extending the variability selection of active galactic nuclei in the W-CDF-S and SERVS/SWIRE region
- 2020
-
In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 634
-
Journal article (peer-reviewed)abstract
- Context. Variability has proven to be a powerful tool to detect active galactic nuclei (AGN) in multi-epoch surveys. The new-generation facilities expected to become operational in the next few years will mark a new era in time-domain astronomy and their wide-field multi-epoch campaigns will favor extensive variability studies.Aims. We present our analysis of AGN variability in the second half of the VST survey of the Wide Chandra Deep Field South, performed in the r band and covering a 2 sq. deg area. The analysis complements a previous work, in which the first half of the area was investigated. We provide a reliable catalog of variable AGN candidates, which will be critical targets in future variability studies.Methods. We selected a sample of optically variable sources and made use of infrared data from the Spitzer mission to validate their nature by means of color-based diagnostics.Results. We obtain a sample of 782 AGN candidates among which 12 are classified as supernovae, 54 as stars, and 232 as AGN. We estimate a contamination less than or similar to 20% and a completeness similar to 38% with respect to mid-infrared selected samples.
|
|
| 20. |
- Zanchettin, Davide, et al.
(author)
-
The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) : experimental design and forcing input data for CMIP6
- 2016
-
In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 9:8, s. 2701-2719
-
Journal article (peer-reviewed)abstract
- The enhancement of the stratospheric aerosol layer by volcanic eruptions induces a complex set of responses causing global and regional climate effects on a broad range of timescales. Uncertainties exist regarding the climatic response to strong volcanic forcing identified in coupled climate simulations that contributed to the fifth phase of the Coupled Model Intercomparison Project (CMIP5). In order to better understand the sources of these model diversities, the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) has defined a coordinated set of idealized volcanic perturbation experiments to be carried out in alignment with the CMIP6 protocol. VolMIP provides a common stratospheric aerosol data set for each experiment to minimize differences in the applied volcanic forcing. It defines a set of initial conditions to assess how internal climate variability contributes to determining the response. VolMIP will assess to what extent volcanically forced responses of the coupled ocean-atmosphere system are robustly simulated by state-of-the-art coupled climate models and identify the causes that limit robust simulated behavior, especially differences in the treatment of physical processes. This paper illustrates the design of the idealized volcanic perturbation experiments in the VolMIP protocol and describes the common aerosol forcing input data sets to be used.
|
|
| 21. |
- Zdanowicz, Christian, 1966-, et al.
(author)
-
Snowmelt, glacial and atmospheric sources of mercury to a subarctic mountain lake catchment, Yukon, Canada
- 2018
-
In: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 238, s. 374-393
-
Journal article (peer-reviewed)abstract
- In montane regions, ongoing and future shrinkage of glacier cover, coupled with a shortening snow cover period, can profoundly alter river hydrology but also lead to the release of long-range contaminants, such as mercury (Hg), deposited and stored in snow and ice. In this study, field data coupled with hydrological and atmospheric models were used to estimate the contributions of atmospherically-deposited Hg released by snow or glacier ice melt, and from direct atmospheric deposition, to Kusawa Lake, in subarctic Yukon, Canada. The estimated net Hg accumulation rate in supraglacial snow obtained from field samples is 0.55 μg m−2 a−1. The direct annual atmospheric Hg flux to Kusawa Lake, obtained from model simulations, and which includes summertime wet deposition, is ∼6 times larger, averaging 3.04 μg m−2 a−1. The estimated mass of Hg from snow/ice meltwater entering the lake annually is 0.6 kg, while direct atmospheric deposition to the lake may contribute a further 0.4 kg, totaling 1.0 kg a−1. Levels of Hg in cores taken from glaciers in the catchment’s headwaters are mostly above expected pre-industrial values, which suggests that some Hg now being released from glaciers is legacy anthropogenic Hg that accumulated in the past 150 years. At present, the delivery of Hg from melting glacial ice is the largest known source to Kusawa Lake, followed by contemporary atmospheric inputs (direct or via runoff). Efforts should be made to quantify other potential sources, such as subglacial meltwater, runoff from wetlands/forest, or melting permafrost, to better constrain the Hg balance in montane lake catchments of this region.
|
|
