| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Asselbergs, Folkert W., et al.
(author)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 4. |
- Johnson, Toby, et al.
(author)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Journal article (peer-reviewed)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 5. |
- Ma, Li-Jun, et al.
(author)
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Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
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Journal article (peer-reviewed)abstract
- Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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| 6. |
- Newton-Cheh, Christopher, et al.
(author)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Journal article (peer-reviewed)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 7. |
- Acero, F., et al.
(author)
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Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
- 2017
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 840:2
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Journal article (peer-reviewed)abstract
- We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Bashitialshaaer, Raed, et al.
(author)
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New Criteria for Brine Discharge Outfalls from Desalination Plants
- 2015
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In: Intakes and Outfalls for Seawater Reverse-Osmosis Desalination Facilities. - 9783319132020 ; , s. 451-467
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Book chapter (pop. science, debate, etc.)abstract
- An efficient method for increasing the dilution rate of brine water discharged into the sea is an inclined negatively buoyant jet from a single port or a multi-diffuser system. Such jets typically arise when brine is discharged from desalination plants. Two small-scale experimental studies were conducted to investigate the behaviour of a dense jet discharged into lighter ambient water. The first experiment concerned the importance of the initial angle of inclined dense jets, where the slope of the flow increased for the maximum levels as a function of this angle. An angle of 60° produced better results than 30° or 45°. An empirical predictive equation was developed based on five geometric quantities to be considered in the design of plants.The second experiment studied the near and intermediate fields of negatively buoyant jets. Dilution in the flow direction was increased by about 10 % and 40 % with bottom slope, and bottom slope together with a 30° jet inclination, respectively. An over 16 % bottom slope experiment and more field work in the future are needed to compare with this result. It was found that an inclination of 30° with a 16 % bottom slope were optimal for the design of brine discharge outfall.
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| 12. |
- Chen, Cheng, et al.
(author)
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Combining camera trap surveys and IUCN range maps to improve knowledge of species distributions
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In: Conservation Biology. - 0888-8892.
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Journal article (peer-reviewed)abstract
- Reliable maps of species distributions are fundamental for biodiversity research and conservation. The International Union for Conservation of Nature (IUCN) range maps are widely recognized as authoritative representations of species’ geographic limits, yet they might not always align with actual occurrence data. In recent area of habitat (AOH) maps, areas that are not habitat have been removed from IUCN ranges to reduce commission errors, but their concordance with actual species occurrence also remains untested. We tested concordance between occurrences recorded in camera trap surveys and predicted occurrences from the IUCN and AOH maps for 510 medium- to large-bodied mammalian species in 80 camera trap sampling areas. Across all areas, cameras detected only 39% of species expected to occur based on IUCN ranges and AOH maps; 85% of the IUCN only mismatches occurred within 200 km of range edges. Only 4% of species occurrences were detected by cameras outside IUCN ranges. The probability of mismatches between cameras and the IUCN range was significantly higher for smaller-bodied mammals and habitat specialists in the Neotropics and Indomalaya and in areas with shorter canopy forests. Our findings suggest that range and AOH maps rarely underrepresent areas where species occur, but they may more often overrepresent ranges by including areas where a species may be absent, particularly at range edges. We suggest that combining range maps with data from ground-based biodiversity sensors, such as camera traps, provides a richer knowledge base for conservation mapping and planning.
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| 13. |
- Chen, Cheng, et al.
(author)
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Global camera trap synthesis highlights the importance of protected areas in maintaining mammal diversity
- 2022
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In: Conservation Letters. - : Wiley. - 1755-263X. ; 15:2
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Journal article (peer-reviewed)abstract
- The establishment of protected areas (PAs) is a central strategy for global biodiversity conservation. While the role of PAs in protecting habitat has been highlighted, their effectiveness at protecting mammal communities remains unclear. We analyzed a global dataset from over 8671 camera traps in 23 countries on four continents that detected 321 medium- to large-bodied mammal species. We found a strong positive correlation between mammal taxonomic diversity and the proportion of a surveyed area covered by PAs at a global scale (β = 0.39, 95% confidence interval [CI] = 0.19–0.60) and in Indomalaya (β = 0.69, 95% CI = 0.19–1.2), as well as between functional diversity and PA coverage in the Nearctic (β = 0.47, 95% CI = 0.09–0.85), after controlling for human disturbances and environmental variation. Functional diversity was only weakly (and insignificantly) correlated with PA coverage at the global scale (β = 0.22, 95% CI = −0.02–0.46), pointing to a need to better understand the functional response of mammal communities to protection. Our study provides important evidence of the global effectiveness of PAs in conserving terrestrial mammals and emphasizes the critical role of area-based conservation in a post-2020 biodiversity framework.
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| 14. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 15. |
- Moore, Casey A., et al.
(author)
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A Full Martian Year of Line-of-Sight Extinction within Gale Crater, Mars as Acquired by the MSL Navcam through sol 900
- 2016
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In: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 264, s. 102-108
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Journal article (peer-reviewed)abstract
- We report on line-of-sight extinction in northern Gale Crater, Mars as seen by the Mars Science Laboratory (MSL) rover, Curiosity from sol 100 to sol 900; a little more than an entire martian year. Navcam images oriented due north, which show the distant crater rim, the near ground and the sky allow the extinction due to dust within the crater to be determined. This line-of sight extinction is compared to a complementary dataset of column extinctions derived from Mastcam. The line-of-sight extinction within the crater is less than the column extinction for the majority of the martian year. This implies that the relatively low mixing ratio of dust within the crater as compared to the atmosphere above the crater rim persists through most of the year. This suggests relatively little mixing between the atmosphere above the crater and the atmosphere inside the crater and suggests that northern Gale Crater is a net sink of dust in the current era. The data does however show a yearly convergence of the line-of-sight extinction and the column-averaged extinction around Ls = 270° – 290°. This suggests that air above the crater mixes with air in the crater at this time, as predicted by mesoscale models. Matching line-of-sight and column extinction values are also seen around Ls ≈ 135°, a season that has only been observed once in this dataset, this is particularly interesting as the Rover Environmental Monitoring Station onboard Curiosity reports increased convective boundary layer heights in the same season.
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| 16. |
- Pellegrini, Adam F.A., et al.
(author)
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Soil carbon storage capacity of drylands under altered fire regimes
- 2023
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In: Nature Climate Change. - 1758-678X. ; 13:10, s. 1089-1094
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Journal article (peer-reviewed)abstract
- The determinants of fire-driven changes in soil organic carbon (SOC) across broad environmental gradients remains unclear, especially in global drylands. Here we combined datasets and field sampling of fire-manipulation experiments to evaluate where and why fire changes SOC and compared our statistical model to simulations from ecosystem models. Drier ecosystems experienced larger relative changes in SOC than humid ecosystems—in some cases exceeding losses from plant biomass pools—primarily explained by high fire-driven declines in tree biomass inputs in dry ecosystems. Many ecosystem models underestimated the SOC changes in drier ecosystems. Upscaling our statistical model predicted that soils in savannah–grassland regions may have gained 0.64 PgC due to net-declines in burned area over the past approximately two decades. Consequently, ongoing declines in fire frequencies have probably created an extensive carbon sink in the soils of global drylands that may have been underestimated by ecosystem models.
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| 17. |
- Pfeffer, M. A., et al.
(author)
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Ground-Based measurements of the 2014-2015 holuhraun volcanic cloud (Iceland)
- 2018
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In: Geosciences (Switzerland). - : MDPI AG. - 2076-3263. ; 8:1
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Journal article (peer-reviewed)abstract
- The 2014-2015 Bárðarbunga fissure eruption at Holuhraun in central Iceland was distinguished by the high emission of gases, in total 9.6 Mt SO 2 , with almost no tephra. This work collates all ground-based measurements of this extraordinary eruption cloud made under particularly challenging conditions: remote location, optically dense cloud with high SO 2 column amounts, low UV intensity, frequent clouds and precipitation, an extensive and hot lava field, developing ramparts, and high-latitude winter conditions. Semi-continuous measurements of SO 2 flux with three scanning DOAS instruments were augmented by car traverses along the ring-road and along the lava. The ratios of other gases/SO 2 were measured by OP-FTIR, MultiGAS, and filter packs. Ratios of SO 2 /HCl = 30-110 and SO 2 /HF = 30-130 show a halogen-poor eruption cloud. Scientists on-site reported extremely minor tephra production during the eruption. OPC and filter packs showed low particle concentrations similar to non-eruption cloud conditions. Three weather radars detected a droplet-rich eruption cloud. Top of eruption cloud heights of 0.3-5.5 km agl were measured with ground-and aircraft-based visual observations, web camera and NicAIR II infrared images, triangulation of scanning DOAS instruments, and the location of SO 2 peaks measured by DOAS traverses. Cloud height and emission rate measurements were critical for initializing gas dispersal simulations for hazard forecasting.
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| 18. |
- Selck, H., et al.
(author)
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Assessing and managing multiple risks in a changing worldThe Roskilde recommendations
- 2017
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In: Environmental Toxicology and Chemistry. - Hoboken, NJ : Wiley. - 0730-7268 .- 1552-8618. ; 36:1, s. 7-16
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Journal article (peer-reviewed)abstract
- Roskilde University (Denmark) hosted a November 2015 workshop, Environmental RiskAssessing and Managing Multiple Risks in a Changing World. This Focus article presents the consensus recommendations of 30 attendees from 9 countries regarding implementation of a common currency (ecosystem services) for holistic environmental risk assessment and management; improvements to risk assessment and management in a complex, human-modified, and changing world; appropriate development of protection goals in a 2-stage process; dealing with societal issues; risk-management information needs; conducting risk assessment of risk management; and development of adaptive and flexible regulatory systems. The authors encourage both cross-disciplinary and interdisciplinary approaches to address their 10 recommendations: 1) adopt ecosystem services as a common currency for risk assessment and management; 2) consider cumulative stressors (chemical and nonchemical) and determine which dominate to best manage and restore ecosystem services; 3) fully integrate risk managers and communities of interest into the risk-assessment process; 4) fully integrate risk assessors and communities of interest into the risk-management process; 5) consider socioeconomics and increased transparency in both risk assessment and risk management; 6) recognize the ethical rights of humans and ecosystems to an adequate level of protection; 7) determine relevant reference conditions and the proper ecological context for assessments in human-modified systems; 8) assess risks and benefits to humans and the ecosystem and consider unintended consequences of management actions; 9) avoid excessive conservatism or possible underprotection resulting from sole reliance on binary, numerical benchmarks; and 10) develop adaptive risk-management and regulatory goals based on ranges of uncertainty. Environ Toxicol Chem 2017;36:7-16. (c) 2016 SETAC
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| 19. |
- Soscia, Stephanie J., et al.
(author)
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The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide
- 2010
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9505-
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Journal article (peer-reviewed)abstract
- Background: The amyloid beta-protein (A beta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. A beta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, A beta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A beta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of A beta and LL-37, an archetypical human AMP. Findings reveal that A beta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A beta levels. Consistent with A beta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A beta antibodies. Conclusions/Significance: Our findings suggest A beta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of A beta-mediated pathology and has important implications for ongoing and future AD treatment strategies.
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