| 1. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
|
|
| 2. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 3. |
- Feng, Ruizhi, et al.
(författare)
-
Mutations in TUBB8 and Human Oocyte Meiotic Arrest.
- 2016
-
Ingår i: The New England journal of medicine. - 1533-4406. ; 374:3, s. 223-232
-
Tidskriftsartikel (refereegranskat)abstract
- Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
|
|
| 4. |
- Li, Furong, et al.
(författare)
-
Towards quantification of Holocene anthropogenic land-cover change in temperate China : A review in the light of pollen-based REVEALS reconstructions of regional plant cover
- 2020
-
Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 203, s. 1-25
-
Forskningsöversikt (refereegranskat)abstract
- In an attempt to quantify Holocene anthropogenic land-cover change in temperate China, we 1) applied the REVEALS model to estimate plant-cover change using 94 pollen records and relative pollen productivity for 27 plant taxa, 2) reviewed earlier interpretation of pollen studies in terms of climate- and human-induced vegetation change, and 3) reviewed information on past land use from archaeological studies. REVEALS achieved a more realistic reconstruction of plant-cover change than pollen percentages in terms of openland versus woodland. The study suggests successive human-induced changes in vegetation cover. The first signs of human-induced land-cover change (crop cultivation, otherwise specified) are found c. 7 ka BP in the temperate deciduous forest, and S and NE Tibetan Plateau (mainly grazing, possibly crop cultivation), 6.5-6 ka BP in the temperate steppe and temperate desert (grazing, uncertain), and 5.5-5 ka BP in the coniferous-deciduous mixed forest, NE subtropical region, and NW Tibetan Plateau (grazing). Further intensification of anthropogenic land-cover change is indicated 5-4.5 ka BP in the E temperate steppe, and S and NE Tibetan Plateau (grazing, cultivation uncertain), 3.5-3 ka BP in S and NE Tibetan Plateau, W temperate steppe, temperate desert (grazing), and NW Tibetan Plateau (probably grazing), and 2.5-2 ka BP in the temperate deciduous forest, N subtropical region, and temperate desert (grazing). These changes generally agree with increased human activity as documented by archaeological studies. REVEALS reconstructions have a stronger potential than biomization to evaluate scenarios of anthropogenic land-cover change such as HYDE, given they are combined with information from archaeological studies.
|
|
| 5. |
- Li, Furong, et al.
(författare)
-
Gridded pollen-based Holocene regional plant cover in temperate and northernsubtropical China suitable for climate modelling
- 2023
-
Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 15:1, s. 95-112
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first gridded and temporally continuous quantitative pollen-based plant-cover reconstruction for temperate and northern subtropical China over the Holocene (11.7 ka to present) obtained by applying the Regional Estimates of VEgetation Abundance from Large Sites (REVEALS) model. The objective is to provide a dataset of pollen-based land cover for the last ca. 12 millennia that is suitable for palaeoclimate modelling and for the evaluation of simulated past vegetation cover from dynamic vegetation models and anthropogenic land-cover change (ALCC) scenarios. The REVEALS reconstruction was achieved using 94 selected pollen records from lakes and bogs at a 1 degrees x 1 degrees spatial scale and a temporal resolution of 500 years between 11.7 and 0.7 ka and in three recent time windows (0.7-0.35 ka, 0.35-0.1 ka, and 0.1 ka to present). The dataset includes REVEALS estimates of cover and their standard errors (SEs) for 27 plant taxa in 75 1 degrees x 1 degrees grid cells distributed within the study region. The 27 plant taxa were also grouped into 6 plant functional types and 3 land-cover types (coniferous trees CT, broadleaved trees BT, and C-3 herbs/open land (C3H/OL)), and their REVEALS estimates of cover and related SEs were calculated. We describe the protocol used for the selection of pollen records and the REVEALS application (with parameter settings) and explain the major rationales behind the protocol. As an illustration, we present, for eight selected time windows, gridded maps of the pollen-based REVEALS estimates of cover for the three land-cover types (CT, BT, and C3H/OL). We then discuss the reliability and limitations of the Chinese dataset of Holocene gridded REVEALS plant cover, and its current and potential uses. The dataset is available at the National Tibetan Plateau Data Center (TPDC; Li, 2022; ).
|
|
| 6. |
- Wang, Haibin, et al.
(författare)
-
Strain in Copper/Ceria Heterostructure Promotes Electrosynthesis of Multicarbon Products
- 2023
-
Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:1, s. 346-354
-
Tidskriftsartikel (refereegranskat)abstract
- Elastic strains in metallic catalysts induce enhanced selectivity for carbon dioxide reduction (CO2R) toward valuable multicarbon (C2+) products. However, under working conditions, the structure of catalysts inevitably undergoes reconstruction, hardly retaining the initial strain. Herein, we present a metal/metal oxide synthetic strategy to introduce and maintain the tensile strain in a copper/ceria heterostructure, enabled by the presence of a thin interface layer of Cu2O/CeO2. The tensile strain in the copper domain and deficient electron environment around interfacial Cu sites resulted in strengthened adsorption of carbonaceous intermediates and promoted*CO dimerization. The strain effect in the copper/ceria heterostructure leads to an improved C2+ selectivity with a maximum Faradaic efficiency of 76.4% and a half-cell power conversion efficiency of 49.1%. The fundamental insights gained from this system can facilitate the rational design of heterostructure catalysts for CO2R.
|
|
| 7. |
- Wang, Xi, et al.
(författare)
-
Self-Constructed Multiple Plasmonic Hotspots on an Individual Fractal to Amplify Broadband Hot Electron Generation
- 2021
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:6, s. 10553-10564
-
Tidskriftsartikel (refereegranskat)abstract
- Plasmonic nanoparticles are ideal candidates for hot-electron-assisted applications, but their narrow resonance region and limited hotspot number hindered the energy utilization of broadband solar energy. Inspired by tree branches, we designed and chemically synthesized silver fractals, which enable self-constructed hotspots and multiple plasmonic resonances, extending the broadband generation of hot electrons for better matching with the solar radiation spectrum. We directly revealed the plasmonic origin, the spatial distribution, and the decay dynamics of hot electrons on the single-particle level by using ab initio simulation, dark-field spectroscopy, pump–probe measurements, and electron energy loss spectroscopy. Our results show that fractals with acute tips and narrow gaps can support broadband resonances (400–1100 nm) and a large number of randomly distributed hotspots, which can provide unpolarized enhanced near field and promote hot electron generation. As a proof-of-concept, hot-electron-triggered dimerization of p-nitropthiophenol and hydrogen production are investigated under various irradiations, and the promoted hot electron generation on fractals was confirmed with significantly improved efficiency.
|
|
| 8. |
- Wu, Xiuchen, et al.
(författare)
-
Exposures to temperature beyond threshold disproportionately reduce vegetation growth in the northern hemisphere
- 2019
-
Ingår i: National Science Review. - : Oxford University Press (OUP). - 2095-5138 .- 2053-714X. ; 6:4
-
Tidskriftsartikel (refereegranskat)abstract
- In recent decades, terrestrial vegetation in the northern hemisphere (NH) has been exposed to warming and more extremely high temperatures. However, the consequences of these changes for terrestrial vegetation growth remain poorly quantified and understood. By examining a satellite-based vegetation index, tree-ring measurements and land-surface model simulations, we discovered a consistent convex pattern in the responses of vegetation growth to temperature exposure (TE) for forest, shrub and grass in both the temperate (30°−50° N) and boreal (50°−70° N) NH during the period of 1982−2012. The response of vegetation growth to TE for the three vegetation types in both the temperate and boreal NH increased convergently with increasing temperature, until vegetation type-dependent temperature thresholds were reached. A TE beyond these temperature thresholds resulted in disproportionately weak positive or even strong negative responses. Vegetation growth in the boreal NH was more vulnerable to extremely high-temperature events than vegetation growth in the temporal NH. The non-linear responses discovered here provide new insights into the dynamics of northern terrestrial ecosystems in a warmer world.
|
|
| 9. |
- Yang, Huiqing, et al.
(författare)
-
Protic Quaternary Ammonium Ionic Liquids for Catalytic Conversion of CO2 into Cyclic Carbonates : A Combined Ab Initio and MD Study
- 2018
-
Ingår i: Industrial & Engineering Chemistry Research. - : AMER CHEMICAL SOC. - 0888-5885 .- 1520-5045. ; 57:21, s. 7121-7129
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanism of CO2 fixation catalyzed by protic hydroxyl-functionalized quaternary ammonium ionic liquids (ILs) is investigated by two different models, the Single-IL model and the Double-IL model. The relative sequence of catalytic activity calculated by the Single-IL model is contradictory with the experimental result. The situation is totally varied when the Double-IL model is utilized. In this system, ILs are not limited to the catalyst but solvent. The ILs are incorporated into the catalytic system to consider the solvent effect rather than by the existing solvent model. When the solvent effect is included, it is better to distinguish the catalytic activity of three ILs. According to the noncovalent interaction and the atoms in molecules analysis, the highest catalytic activity of tris(2-hydroxyethyl)ammonium bromide ([HTEA]Br) is attributed to its strongest nucleophilic attack and moderate hydrogen bond interaction between IL and reactant. It is necessary to consider the interaction between ILs to get a reliable result. Moreover, the solvent effect aroused by ILs should be carefully considered.
|
|
| 10. |
- Abelev, Betty, et al.
(författare)
-
Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
|
|
