| 1. |
- Niemi, MEK, et al.
(author)
-
- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
-
Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 4. |
- Thomas, HS, et al.
(author)
-
- 2019
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swepub:Mat__t
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| 5. |
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| 6. |
- Dornelas, M., et al.
(author)
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BioTIME: A database of biodiversity time series for the Anthropocene
- 2018
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:7, s. 760-786
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Journal article (peer-reviewed)abstract
- Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)). Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
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| 7. |
- Weiner, D. J., et al.
(author)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
-
Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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| 8. |
- Anney, R. J. L., et al.
(author)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
-
In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Journal article (peer-reviewed)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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| 9. |
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| 10. |
- van Rheenen, W, et al.
(author)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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| 11. |
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| 12. |
- Jakosky, B. M., et al.
(author)
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MAVEN observations of the response of Mars to an interplanetary coronal mass ejection
- 2015
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
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Journal article (peer-reviewed)abstract
- Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.
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| 13. |
- Jakosky, B. M., et al.
(author)
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The Mars Atmosphere and Volatile Evolution (MAVEN) Mission
- 2015
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 195:1-4, s. 3-48
-
Research review (peer-reviewed)abstract
- The MAVEN spacecraft launched in November 2013, arrived at Mars in September 2014, and completed commissioning and began its one-Earth-year primary science mission in November 2014. The orbiter's science objectives are to explore the interactions of the Sun and the solar wind with the Mars magnetosphere and upper atmosphere, to determine the structure of the upper atmosphere and ionosphere and the processes controlling it, to determine the escape rates from the upper atmosphere to space at the present epoch, and to measure properties that allow us to extrapolate these escape rates into the past to determine the total loss of atmospheric gas to space through time. These results will allow us to determine the importance of loss to space in changing the Mars climate and atmosphere through time, thereby providing important boundary conditions on the history of the habitability of Mars. The MAVEN spacecraft contains eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space. In addition, it contains an Electra relay that will allow it to relay commands and data between spacecraft on the surface and Earth.
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| 14. |
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| 15. |
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| 16. |
- Behm, K. T., et al.
(author)
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A spectrometer for ultrashort gamma-ray pulses with photon energies greater than 10 MeV
- 2018
-
In: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 89:11
-
Journal article (peer-reviewed)abstract
- © 2018 Author(s). We present a design for a pixelated scintillator based gamma-ray spectrometer for non-linear inverse Compton scattering experiments. By colliding a laser wakefield accelerated electron beam with a tightly focused, intense laser pulse, gamma-ray photons up to 100 MeV energies and with few femtosecond duration may be produced. To measure the energy spectrum and angular distribution, a 33 × 47 array of cesium-iodide crystals was oriented such that the 47 crystal length axis was parallel to the gamma-ray beam and the 33 crystal length axis was oriented in the vertical direction. Using an iterative deconvolution method similar to the YOGI code, modeling of the scintillator response using GEANT4 and fitting to a quantum Monte Carlo calculated photon spectrum, we are able to extract the gamma ray spectra generated by the inverse Compton interaction.
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| 17. |
- Cole, J. M., et al.
(author)
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Experimental Evidence of Radiation Reaction in the Collision of a High-Intensity Laser Pulse with a Laser-Wakefield Accelerated Electron Beam
- 2018
-
In: Physical Review X. - 2160-3308. ; 8:1
-
Journal article (peer-reviewed)abstract
- The dynamics of energetic particles in strong electromagnetic fields can be heavily influenced by the energy loss arising from the emission of radiation during acceleration, known as radiation reaction. When interacting with a high-energy electron beam, today's lasers are sufficiently intense to explore the transition between the classical and quantum radiation reaction regimes. We present evidence of radiation reaction in the collision of an ultrarelativistic electron beam generated by laser-wakefield acceleration (μ 500 MeV) with an intense laser pulse (a0 > 10). We measure an energy loss in the postcollision electron spectrum that is correlated with the detected signal of hard photons (γ rays), consistent with a quantum description of radiation reaction. The generated γ rays have the highest energies yet reported from an all-optical inverse Compton scattering scheme, with critical energy > 30 MeV.
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| 18. |
- Ridgers, C. P., et al.
(author)
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Signatures of quantum effects on radiation reaction in laser-electron-beam collisions
- 2017
-
In: Journal of Plasma Physics. - : Cambridge University Press (CUP). - 0022-3778 .- 1469-7807. ; 83:5
-
Journal article (peer-reviewed)abstract
- Two signatures of quantum effects on radiation reaction in the collision of a similar to GeV electron beam with a high intensity (>3 x 10(20) W cm(-2)) laser pulse have been considered. We show that the decrease in the average energy of the electron beam may be used to measure the Gaunt factor g for synchrotron emission. We derive an equation for the evolution of the variance in the energy of the electron beam in the quantum regime, i.e. quantum efficiency parameter eta (sic) 1. We show that the evolution of the variance may be used as a direct measure of the quantum stochasticity of the radiation reaction and determine the parameter regime where this is observable. For example, stochastic emission results in a 25 % increase in the standard deviation of the energy spectrum of a GeV electron beam, 1 fs after it collides with a laser pulse of intensity 10(21) W cm(-2). This effect should therefore be measurable using current high-intensity laser systems.
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| 19. |
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| 20. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
-
Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 21. |
- Zheng, J., et al.
(author)
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Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures
- 2019
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:10, s. 1824-1836
-
Journal article (peer-reviewed)abstract
- In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (beta = 0.20, p = 4.6 x 10(-49)) and GALNT1 (beta = 0.11 per G allele, p = 4.4 x 10(-11)). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (beta = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (beta = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (beta = 0.11, 95% CI 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis. (c) 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
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| 22. |
- Abbott, R., et al.
(author)
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Hybridization and speciation
- 2013
-
In: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 26:2, s. 229-246
-
Research review (peer-reviewed)abstract
- Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.
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| 23. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
-
Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 24. |
- Baird, C. D., et al.
(author)
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Realising single-shot measurements of quantum radiation reaction in high-intensity lasers
- 2019
-
In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 21:5
-
Journal article (peer-reviewed)abstract
- Modern laser technology is now sufficiently advanced that collisions between high-intensity laser pulses and laser-wakefield-accelerated (LWFA) electron beams can reach the strong-field regime, so that it is possible to measure the transition between the classical and quantum regimes of light-matter interactions. However, the energy spectrum of LWFA electron beams can fluctuate significantly from shot to shot, making it difficult to clearly discern quantum effects in radiation reaction (RR), for example. Here we show how this can be accomplished in only a single laser shot. A millimetre-scale pre-collision drift allows the electron beam to expand to a size larger than the laser focal spot and develop a correlation between transverse position and angular divergence. In contrast to previous studies, this means that a measurement of the beam's energy-divergence spectrum automatically distinguishes components of the beam that hit or miss the laser focal spot and therefore do and do not experience RR.
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| 25. |
- Hop, Paul J., et al.
(author)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
-
In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 26. |
- Maasri, Alain, et al.
(author)
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A global agenda for advancing freshwater biodiversity research
- 2022
-
In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 255-263
-
Journal article (peer-reviewed)abstract
- Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.
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| 27. |
- Anney, Richard, et al.
(author)
-
Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
-
Journal article (peer-reviewed)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 28. |
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| 29. |
- Foote, Andrew D., et al.
(author)
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Genome-culture coevolution promotes rapid divergence of killer whale ecotypes
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.
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| 30. |
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| 31. |
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| 32. |
- Tamborero, D, et al.
(author)
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The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology
- 2022
-
In: Nature cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 251-
-
Journal article (peer-reviewed)abstract
- There is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and technological platform to share and harness next-generation sequencing data. Automating the interpretation and reporting of sequencing results decrease the need for time-consuming manual procedures that are prone to errors. The adoption of an expert-agreed process to systematically link tumor molecular profiles with clinical actions promotes consistent decision-making and structured data capture across the connected centers. The use of information-rich patient reports with interactive content facilitates collaborative discussion of complex cases during virtual molecular tumor board meetings. Overall, streamlined digital systems like the MTBP are crucial to better address the challenges brought by precision oncology and accelerate the use of emerging biomarkers.
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| 33. |
- Westwood, S., et al.
(author)
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Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and F-18 -Flutemetamol PET Scan Result
- 2018
-
In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 10
-
Journal article (peer-reviewed)abstract
- Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer's disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) A beta and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/A beta(42) (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [F-18]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF A beta(42) measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/A beta(42) (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C -IV and fibrinogen f, chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/A beta(42). There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF A beta(42) (P approximate to 0.05), while both Al AT and clusterin were nominally significantly associated with CSF A beta(42) (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important.
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| 34. |
- Casey, Jillian P, et al.
(author)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
-
In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 35. |
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| 36. |
- Pinto, Dalila, et al.
(author)
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Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.
- 2014
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In: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 94:5, s. 677-694
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Journal article (peer-reviewed)abstract
- Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0× 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7× 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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| 37. |
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| 38. |
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| 39. |
- Chaplin-Kramer, R., et al.
(author)
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Transformation for inclusive conservation : Evidence on values, decisions, and impacts in protected areas
- 2023
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In: Current Opinion in Environmental Sustainability. - : Elsevier. - 1877-3435 .- 1877-3443. ; 64
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Journal article (peer-reviewed)abstract
- As countries consider new area-based conservation targets under the Convention on Biological Diversity, protected areas (PAs) and their impacts on people and nature are coming under increasing scrutiny. We review the evidence base on PA impacts, combining the findings from existing rigorous impact evaluations with local case studies developed for this study. We identify characteristics of PA establishment and management that improve the sustainability of biodiversity conservation and justice for local communities. We find that recognizing and respecting local values and knowledge about natural resource stewardship, colearning, and comanagement are key to achieving positive impacts for nature and people. Transforming PA governance toward more inclusive conservation depends upon the ability of PAs to be designed and implemented around the values and needs of local people.
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| 40. |
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| 41. |
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| 42. |
- Dominoni, Davide M., et al.
(author)
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Why conservation biology can benefit from sensory ecology
- 2020
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In: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 4:4, s. 502-511
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Journal article (peer-reviewed)abstract
- Anthropogenic sensory pollutants, such as noise, light and chemicals, are affecting biodiversity. This Perspective uses an understanding of animal sensory ecology to explore how these impacts can be mitigated. Global expansion of human activities is associated with the introduction of novel stimuli, such as anthropogenic noise, artificial lights and chemical agents. Progress in documenting the ecological effects of sensory pollutants is weakened by sparse knowledge of the mechanisms underlying these effects. This severely limits our capacity to devise mitigation measures. Here, we integrate knowledge of animal sensory ecology, physiology and life history to articulate three perceptual mechanisms-masking, distracting and misleading-that clearly explain how and why anthropogenic sensory pollutants impact organisms. We then link these three mechanisms to ecological consequences and discuss their implications for conservation. We argue that this framework can reveal the presence of 'sensory danger zones', hotspots of conservation concern where sensory pollutants overlap in space and time with an organism's activity, and foster development of strategic interventions to mitigate the impact of sensory pollutants. Future research that applies this framework will provide critical insight to preserve the natural sensory world.
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| 43. |
- Hooper, Rebecca, et al.
(author)
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Host-derived population genomics data provides insights into bacterial and diatom composition of the killer whale skin
- 2019
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In: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 28:2, s. 484-502
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Journal article (peer-reviewed)abstract
- Recent exploration into the interactions and relationship between hosts and their microbiota has revealed a connection between many aspects of the host's biology, health and associated micro-organisms. Whereas amplicon sequencing has traditionally been used to characterize the microbiome, the increasing number of published population genomics data sets offers an underexploited opportunity to study microbial profiles from the host shotgun sequencing data. Here, we use sequence data originally generated from killer whale Orcinus orca skin biopsies for population genomics, to characterize the skin microbiome and investigate how host social and geographical factors influence the microbial community composition. Having identified 845 microbial taxa from 2.4 million reads that did not map to the killer whale reference genome, we found that both ecotypic and geographical factors influence community composition of killer whale skin microbiomes. Furthermore, we uncovered key taxa that drive the microbiome community composition and showed that they are embedded in unique networks, one of which is tentatively linked to diatom presence and poor skin condition. Community composition differed between Antarctic killer whales with and without diatom coverage, suggesting that the previously reported episodic migrations of Antarctic killer whales to warmer waters associated with skin turnover may control the effects of potentially pathogenic bacteria such as Tenacibaculum dicentrarchi. Our work demonstrates the feasibility of microbiome studies from host shotgun sequencing data and highlights the importance of metagenomics in understanding the relationship between host and microbial ecology.
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| 44. |
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| 45. |
- Rayner, Matt J., et al.
(author)
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Using miniaturized radiotelemetry to discover the breeding grounds of the endangered New Zealand Storm Petrel Fregetta maoriana
- 2015
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In: Ibis. - : Wiley. - 0019-1019. ; 157:4, s. 754-766
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Journal article (peer-reviewed)abstract
- Identification of breeding sites remains a critical step in species conservation, particularly in procellariiform seabirds whose threat status is of global concern. We designed and conducted an integrative radiotelemetry approach to uncover the breeding grounds of the critically endangered New Zealand Storm Petrel Fregetta maoriana (NZSP), a species considered extinct before its rediscovery in 2003. Solar-powered automated radio receivers and hand-held telemetry were used to detect the presence of birds on three island groups in the Hauraki Gulf near Auckland, New Zealand. At least 11 NZSP captured and radiotagged at sea were detected at night near Te Hauturu-o-Toi/Little Barrier Island with the detection of an incubating bird leading to the discovery of the first known breeding site for this species. In total, four NZSP breeding burrows were detected under mature forest canopy and three adult NZSP and two NZSP chicks were ringed. Telemetry data indicated NZSP showed strong moonlight avoidance behaviour over the breeding site, had incubation shifts of approximately 5days and had a breeding season extending from February to June/July, a different season from other Procellariiformes in the region. Radiotelemetry, in combination with rigorously collected field data on species distribution, offers a valuable technique for locating breeding grounds of procellariiform seabirds and gaining insights into breeding biology while minimizing disturbance to sensitive species or damage to fragile habitat. Our study suggests an avenue for other breeding ground searches in one of the most threatened avian Orders, and highlights the general need for information on the location of breeding sites and understanding the breeding biology in data-deficient birds.
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| 46. |
- Sim, Thomas G., et al.
(author)
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Regional variability in peatland burning at mid-to high-latitudes during the Holocene
- 2023
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In: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 305
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Journal article (peer-reviewed)abstract
- Northern peatlands store globally-important amounts of carbon in the form of partly decomposed plant detritus. Drying associated with climate and land-use change may lead to increased fire frequency and severity in peatlands and the rapid loss of carbon to the atmosphere. However, our understanding of the patterns and drivers of peatland burning on an appropriate decadal to millennial timescale relies heavily on individual site-based reconstructions. For the first time, we synthesise peatland macrocharcoal re-cords from across North America, Europe, and Patagonia to reveal regional variation in peatland burning during the Holocene. We used an existing database of proximal sedimentary charcoal to represent regional burning trends in the wider landscape for each region. Long-term trends in peatland burning appear to be largely climate driven, with human activities likely having an increasing influence in the late Holocene. Warmer conditions during the Holocene Thermal Maximum (similar to 9e6 cal. ka BP) were associated with greater peatland burning in North America's Atlantic coast, southern Scandinavia and the Baltics, and Patagonia. Since the Little Ice Age, peatland burning has declined across North America and in some areas of Europe. This decline is mirrored by a decrease in wider landscape burning in some, but not all sub-regions, linked to fire-suppression policies, and landscape fragmentation caused by agricultural expansion. Peatlands demonstrate lower susceptibility to burning than the wider landscape in several instances, probably because of autogenic processes that maintain high levels of near-surface wetness even during drought. Nonetheless, widespread drying and degradation of peatlands, particularly in Europe, has likely increased their vulnerability to burning in recent centuries. Consequently, peatland restoration efforts are important to mitigate the risk of peatland fire under a changing climate. Finally, we make recommendations for future research to improve our understanding of the controls on peatland fires.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 47. |
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| 48. |
- Yaka, Reyhan, et al.
(author)
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Variable kinship patterns in Neolithic Anatolia revealed by ancient genomes
- 2021
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In: Current Biology. - : Cell Press. - 0960-9822 .- 1879-0445. ; 31:11, s. 2455-2468.e18
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Journal article (peer-reviewed)abstract
- The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,(1) mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,(2) household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Asxikli Hoyuk and Catalhoyuk. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Asxikli Hoyuk and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Catalhoyuk and Barcin, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Catalhoyuk,(3-5) and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.
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