| 1. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 3. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 4. |
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| 5. |
- Pi, X. H., et al.
(author)
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Chlorophyll-a concentrations in 82 large alpine lakes on the Tibetan Plateau during 2003-2017: temporal-spatial variations and influencing factors
- 2021
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In: International Journal of Digital Earth. - : Informa UK Limited. - 1753-8947 .- 1753-8955. ; 14:6, s. 714-735
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Journal article (peer-reviewed)abstract
- As essential parts of the unique ecosystem of Tibetan Plateau (TP), the sizes and associated physical properties of alpine lakes have long been investigated. However, little is known about one of the most critical biogeochemical properties, i.e. the Chlorophyll-a (Chl-a) concentrations. Here, for the first time, we presented a comprehensive investigation of the temporal-spatial variations in Chl-a in 82 lakes (>50 km(2)) across the entire TP region, based on MODIS observations in the period of 2003-2017. The results showed that the 82 lakes exhibited an average long-term mean Chl-a of 3.3 +/- 4.3 mg m(-3), with high Chl-a lakes concentrated in the eastern and southern inner TP basin and northeastern parts of the TP. An interannual trend analysis revealed that lakes exhibiting (significantly) decreasing Chl-a trends and (significantly) increasing Chl-a trends were comparable in numbers but differed in distribution patterns. A correlation analysis indicated that at least 70% of the interannual variability in Chl-a values of lakes was significantly correlated with one of the four environmental factors (wind speed, ice cover duration, lake water surface temperature and surface runoff) and lake size. In addition, glacier meltwater tended to reduce lake Chl-a while salinity levels showed minor influences.
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| 6. |
- Chang, Kuang Yu, et al.
(author)
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Substantial hysteresis in emergent temperature sensitivity of global wetland CH4 emissions
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2266-2266
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Journal article (peer-reviewed)abstract
- Wetland methane (CH4) emissions ([Formula: see text]) are important in global carbon budgets and climate change assessments. Currently, [Formula: see text] projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent [Formula: see text] temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that [Formula: see text] are often controlled by factors beyond temperature. Here, we evaluate the relationship between [Formula: see text] and temperature using observations from the FLUXNET-CH4 database. Measurements collected across the globe show substantial seasonal hysteresis between [Formula: see text] and temperature, suggesting larger [Formula: see text] sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH4 production are thus needed to improve global CH4 budget assessments.
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| 7. |
- Creely, A. J., et al.
(author)
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Overview of the SPARC tokamak
- 2020
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In: Journal of Plasma Physics. - 0022-3778 .- 1469-7807. ; 86:5
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Journal article (peer-reviewed)abstract
- The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field (B-0 = 12.2 T), compact (R-0 = 1.85 m, a = 0.57 m), superconducting, D-T tokamak with the goal of producing fusion gain Q > 2 from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of Q > 2 is achievable with conservative physics assumptions (H-98,H- y2 = 0.7) and, with the nominal assumption of H-98,H- y2 = 1, SPARC is projected to attain Q approximate to 11 and P-fusion approximate to 140 MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density (< n(e)> approximate to 3 x 10(20) m(-3)), high temperature (< Te > approximate to 7 keV) and high power density (P-fusion/V-plasma approximate to 7 MWm(-3)) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
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| 8. |
- Laisk, Triin, et al.
(author)
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The genetic architecture of sporadic and multiple consecutive miscarriage.
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P=3.2 × 10-8, odds ratio (OR)=1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF=6.4%, P=1.3 × 10-8, OR=1.7; rs143445068, MAF=0.8%, P=5.2 × 10-9, OR=3.4; rs183453668, MAF=0.5%, P=2.8 × 10-8, OR=3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.
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| 9. |
- Liu, Y., et al.
(author)
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Increases in China's wind energy production from the recovery of wind speed since 2012
- 2022
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 17:11
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Journal article (peer-reviewed)abstract
- China has realized a 56-fold increase in installed wind capacity, from 5.9 GW in 2007 to 328 GW in 2021. In addition to increasing installed capacity, plans to substantially increase wind energy production for climate change mitigation also depend on future wind speeds, which strongly influences the efficiencies of installed turbines within individual wind farms. A reversal in globally decreasing wind speeds over several decades has been reported previously. However, subsequent studies using other data sources reported only a slight increase or no reversal in China. These uncertainties regarding China's wind energy production hamper estimates of wind energy production potential. Here, our analysis of quality-controlled wind speed measurements from in-situ stations shows that the wind speed decline in China reversed significantly since 2012 (P < 0.001), but with substantial spatio-temporal variability. We further estimated the capacity factor (CF) growth and the wind power gain solely associated with the changes in wind speed ranges from 31.6 to 56.5 TWh yr(-1) based on the 2019 installed capacity. This estimate explains 22.0%-39.3% of the rapid increase in wind generation CF in China during 2012-2019. The result implies that the site selection of wind farms should consider both current wind situation and future wind speed trends. Further studies are needed to understand the driving factor of wind speed recovery in support of the wind energy industry.
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| 10. |
- Liu, Y., et al.
(author)
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Inorganic carbon and alkalinity biogeochemistry and fluxes in an intertidal beach aquifer: Implications for ocean acidification
- 2021
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In: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 595
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Journal article (peer-reviewed)abstract
- While submarine groundwater discharge (SGD) is well known to release large amounts of dissolved nutrients and organic carbon into the ocean, the contribution of SGD to the marine inorganic carbon cycle is poorly understood. Here, the biogeochemistry of inorganic carbon in an intertidal aquifer and related SGD-derived fluxes into Tolo Harbor, Hong Kong was investigated over tidal and seasonal time scales. The results revealed the production of total alkalinity (TAlk) and dissolved inorganic carbon (DIC) in the intertidal aquifer over the entire salinity range. The locally produced TAlk and DIC in the intertidal aquifer contributed to >50% of the TAlk and DIC discharged with SGD to the ocean. The distributions of TAlk and DIC in the transition (mangrove) and high salinity (bare beach) zones were different due to the distinct hydrogeological and geochemical conditions. In the organic-rich mangrove zone, TAlk and DIC productions were driven by biotic processes such as aerobic respiration, denitrification, and sulfate reduction. In the organic-poor bare beach zone, TAlk and DIC productions were likely driven by abiotic processes such as precipitation/dissolution of carbonate minerals. Temperature, pH, physical mixing, and iron cycling in the intertidal aquifer also considerably influenced the carbonate biogeochemistry. TAlk inventory in the intertidal aquifer was seasonally stable but TAlk discharged with SGD was similar to 60% greater in the wet season than in the dry season (73.3 vs. 45.6 mol d(-1) per m coastline). The DIC inventory in the intertidal aquifer and DIC discharged with SGD were similar to 24% and 95% higher, respectively, in the wet season than dry season. Overall, through analyzing TAlk:DIC ratios and related fluxes, SGD was thought to reduce the CO2 buffering capacity of the receiving ocean, and act as a local driver of ocean acidification.
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