| 1. |
|
|
| 2. |
- Teumer, A, et al.
(författare)
-
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
-
Tidskriftsartikel (refereegranskat)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. |
- Wuttke, Matthias, et al.
(författare)
-
A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
-
Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 4. |
|
|
| 5. |
- Dall'Osto, M., et al.
(författare)
-
Novel insights on new particle formation derived from a pan-european observing system
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
- De Cicco, D., et al.
(författare)
-
Optically variable AGN in the three-year VST survey of the COSMOS field
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 627
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 7. |
|
|
| 8. |
- Zanchettin, Davide, et al.
(författare)
-
The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) : experimental design and forcing input data for CMIP6
- 2016
-
Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 9:8, s. 2701-2719
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 9. |
- Zdanowicz, Christian, 1966-, et al.
(författare)
-
Snowmelt, glacial and atmospheric sources of mercury to a subarctic mountain lake catchment, Yukon, Canada
- 2018
-
Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 238, s. 374-393
-
Tidskriftsartikel (refereegranskat)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.
|
|
