| 1. |
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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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.
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| 5. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 7. |
- Fortier, A., et al.
(författare)
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CHEOPS in-flight performance: A comprehensive look at the first 3.5 yr of operations
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Context. Since the discovery of the first exoplanet almost three decades ago, the number of known exoplanets has increased dramatically. By beginning of the 2000s it was clear that dedicated facilities to advance our studies in this field were needed. The CHaracterising ExOPlanet Satellite (CHEOPS) is a space telescope specifically designed to monitor transiting exoplanets orbiting bright stars. In September 2023, CHEOPS completed its nominal mission duration of 3.5 yr and remains in excellent operational conditions. As a testament to this, the mission has been extended until the end of 2026. Aims. Scientific and instrumental data have been collected throughout in-orbit commissioning and nominal operations, enabling a comprehensive analysis of the missiona's performance. In this article, we present the results of this analysis with a twofold goal. First, we aim to inform the scientific community about the present status of the mission and what can be expected as the instrument ages. Secondly, we intend for this publication to serve as a legacy document for future missions, providing insights and lessons learned from the successful operation of CHEOPS. Methods. To evaluate the instrument performance in flight, we developed a comprehensive monitoring and characterisation (M&C) programme. It consists of dedicated observations that allow us to characterise the instrumenta's response and continuously monitor its behaviour. In addition to the standard collection of nominal science and housekeeping data, these observations provide valuable input for detecting, modelling, and correcting instrument systematics, discovering and addressing anomalies, and comparing the instrumenta's actual performance with expectations. Results. The precision of the CHEOPS measurements has enabled the mission objectives to be met and exceeded. The satellitea's performance remains stable and reliable, ensuring accurate data collection throughout its operational life. Careful modelling of the instrumental systematics allows the data quality to be significantly improved during the light curve analysis phase, resulting in more precise scientific measurements. Conclusions. CHEOPS is compliant with the driving scientific requirements of the mission. Although visible, the ageing of the instrument has not affected the missiona's performance. The satellitea's capabilities remain robust, and we are confident that we will continue to acquire high-quality data during the mission extension.
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| 8. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 9. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 10. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 11. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 12. |
- Nava, Veronica, et al.
(författare)
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Plastic debris in lakes and reservoirs
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 619:7969, s. 317-322
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Tidskriftsartikel (refereegranskat)abstract
- Plastic debris is thought to be widespread in freshwater ecosystems globally(1). However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging(2,3). Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 mu m) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris(4). Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.
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| 13. |
- Ocke, M. C., et al.
(författare)
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Energy intake and sources of energy intake in the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 3-15
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe energy intake and its macronutrient and food sources among 27 regions in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 subjects aged 35-74 years were administered a standardized 24-h dietary recall. Intakes of macronutrients (g/day) and energy (kcal/day) were estimated using standardized national nutrient databases. Mean intakes were weighted by season and day of the week and were adjusted for age, height and weight, after stratification by gender. Extreme low- and high-energy reporters were identified using Goldberg's cutoff points (ratio of energy intake and estimated basal metabolic rate <0.88 or >2.72), and their effects on macronutrient and energy intakes were studied. Results: Low-energy reporting was more prevalent in women than in men. The exclusion of extreme-energy reporters substantially lowered the EPIC-wide range in mean energy intake from 2196-2877 to 2309-2866 kcal among men. For women, these ranges were 1659-2070 and 1873-2108 kcal. There was no north-south gradient in energy intake or in the prevalence of low-energy reporting. In most centres, cereals and cereal products were the largest contributors to energy intake. The food groups meat, dairy products and fats and oils were also important energy sources. In many centres, the highest mean energy intakes were observed on Saturdays. Conclusions: These data highlight and quantify the variations and similarities in energy intake and sources of energy intake among 10 European countries. The prevalence of low-energy reporting indicates that the study of energy intake is hampered by the problem of underreporting. European Journal of Clinical Nutrition (2009) 63, S3-S15; doi: 10.1038/ejcn.2009.72
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| 14. |
- Tiegs, Scott D., et al.
(författare)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 15. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 16. |
- Costello, David M., et al.
(författare)
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Global patterns and controls of nutrient immobilization on decomposing cellulose in riverine ecosystems
- 2022
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Ingår i: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:3
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Tidskriftsartikel (refereegranskat)abstract
- Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter.
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| 17. |
- Potapov, Anton M., et al.
(författare)
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Global fine-resolution data on springtail abundance and community structure
- 2024
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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| 18. |
- Abend, Sven, et al.
(författare)
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Terrestrial very-long-baseline atom interferometry : Workshop summary
- 2024
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Ingår i: AVS Quantum Science. - : American Institute of Physics (AIP). - 2639-0213. ; 6:2
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Forskningsöversikt (refereegranskat)abstract
- This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more kilometer--scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.
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| 19. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Hladyz, Sally, et al.
(författare)
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Stream ecosystem functioning in an agricultural landscape : the importance of terrestrial-aquatic linkages
- 2011
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Ingår i: Ecosystems in a human-modified landscape. - San Diego : Academic Press. - 9780123747945 ; 44, s. 211-276
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Bokkapitel (refereegranskat)abstract
- The loss of native riparian vegetation and its replacement with non-native species or grazing land for agriculture is a worldwide phenomenon, but one that is prevalent in Europe, reflecting the heavily-modified nature of the continent's landscape. The consequences of these riparian alterations for freshwater ecosystems remain largely unknown, largely because bioassessment has traditionally focused on the impacts of organic pollution on community structure. We addressed the need for a broader perspective, which encompasses changes at the catchment scale, by comparing ecosystem processes in woodland reference sites with those with altered riparian zones. We assessed a range of riparian modifications, including clearance for pasture and replacement of woodland with a range of low diversity plantations, in 100 streams to obtain a continental-scale perspective of the major types of alterations across Europe. Subsequently, we focused on pasture streams, as an especially prevalent widespread riparian alteration, by characterising their structural (e.g. invertebrate and fish communities) and functional (e.g. litter decomposition, algal production, herbivory) attributes in a country (Ireland) dominated by this type of landscape modification, via field and laboratory experiments. We found that microbes became increasingly important as agents of decomposition relative to macrofauna (invertebrates) in impacted sites in general and in pasture streams in particular. Resource quality of grass litter (e.g., carbon : nutrient ratios, lignin and cellulose content) was a key driver of decomposition rates in pasture streams. These systems also relied more heavily on autochthonous algal production than was the case in woodland streams, which were more detrital based. These findings suggest that these pasture streams might be fundamentally different from their native, ancestral woodland state, with a shift towards greater reliance on autochthonous-based processes. This could have a destabilizing effect on the dynamics of the food web relative to the slower, detrital-based pathways that dominate in woodland streams.
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| 21. |
- Naska, A, et al.
(författare)
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Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.
- 2011
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 35:3, s. 416-426
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants. METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders. RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake. CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.
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| 22. |
- Pinto, Dalila, et al.
(författare)
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Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.
- 2014
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Ingår i: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 94:5, s. 677-694
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Tidskriftsartikel (refereegranskat)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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| 23. |
- Potapov, Anton M., et al.
(författare)
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Globally invariant metabolism but density-diversity mismatch in springtails
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.
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| 24. |
- Prusakov, Pavel, et al.
(författare)
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A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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| 25. |
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| 26. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)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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| 27. |
- Augustin, K, et al.
(författare)
-
Green tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study.
- 2009
-
Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 60:3, s. 103-108
-
Tidskriftsartikel (refereegranskat)abstract
- Green tea catechins (GTC) have been shown to inhibit the activities of enzymes involved in folate uptake. Hence, regular green tea drinkers may be at risk of impaired folate status. The present experiments aimed at studying the impact of dietary GTC on folate concentrations and metabolism. In a human pilot study (parallel design) healthy men consumed for 3 weeks 6 capsules (approximately 670 mg GTC) per day (2 capsules with each principal meal) containing aqueous extracts of the leaves of Camellia sinensis (n=17) or placebo (n=16). No differences in plasma folate concentrations were observed between treatments. We further fed groups of 10 male rats diets fortified with 0, 0.05, 0.5, 1, or 5 g GTC/kg for 6 weeks. Only at the highest intake, GTC significantly decreased serum 5-methyl-tetrahydrofolate concentrations in rats, while mRNA concentrations of reduced folate carrier, proton-coupled folate transporter/heme carrier protein 1, and dihydrofolate reductase (DHFR) remained unchanged in intestinal mucosa. Using an in vitro enzyme activity assay, we observed a time- and dose-dependent inhibition of DHFR activity by epigallocatechin gallate and a green tea extract. Our data suggest that regular green tea consumption is unlikely to impair folate status in healthy males, despite the DHFR inhibitory activity of GTC.
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| 28. |
- Boyero, Luz, et al.
(författare)
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Riparian plant litter quality increases with latitude
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to diverge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107 degrees) in litter traits (nutrient concentrations; physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce 'syndromes' resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen: phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.
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| 29. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
-
Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 30. |
- De Marco, O., et al.
(författare)
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The messy death of a multiple star system and the resulting planetary nebula as observed by JWST
- 2022
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:12, s. 1421-1432
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Tidskriftsartikel (refereegranskat)abstract
- Planetary nebulae—the ejected envelopes of red giant stars—provide us with a history of the last, mass-losing phases of 90% of stars initially more massive than the Sun. Here we analyse images of the planetary nebula NGC 3132 from the James Webb Space Telescope (JWST) Early Release Observations. A structured, extended hydrogen halo surrounding an ionized central bubble is imprinted with spiral structures, probably shaped by a low-mass companion orbiting the central star at about 40–60 au. The images also reveal a mid-infrared excess at the central star, interpreted as a dusty disk, which is indicative of an interaction with another closer companion. Including the previously known A-type visual companion, the progenitor of the NGC 3132 planetary nebula must have been at least a stellar quartet. The JWST images allow us to generate a model of the illumination, ionization and hydrodynamics of the molecular halo, demonstrating the power of JWST to investigate complex stellar outflows. Furthermore, new measurements of the A-type visual companion allow us to derive the value for the mass of the progenitor of a central star with excellent precision: 2.86 ± 0.06 M⊙. These results serve as pathfinders for future JWST observations of planetary nebulae, providing unique insight into fundamental astrophysical processes including colliding winds and binary star interactions, with implications for supernovae and gravitational-wave systems.
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| 31. |
- Fortner, Renee T., et al.
(författare)
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Ovarian Cancer Risk Factor Associations by Primary Anatomic Site : The Ovarian Cancer Cohort Consortium
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 29:10, s. 2010-2018
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.
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| 32. |
- Halbritter, Aud H., et al.
(författare)
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Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Perú
- 2024
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Ingår i: SCIENTIFIC DATA. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families.
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| 33. |
- Hoencamp, Claire, et al.
(författare)
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3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- 2021
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6545, s. 984-989
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
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| 34. |
- Jacobs, Alan M., et al.
(författare)
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The Qualitative Transparency Deliberations : Insights and Implications
- 2021
-
Ingår i: Perspectives on Politics. - 1537-5927 .- 1541-0986. ; 19:1, s. 171-208
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process-the Qualitative Transparency Deliberations (QTD)-involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups' final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency's promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports-the full versions of which can be found in the Supplementary Materials-offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate-as understood by relevant research communities-to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.(1)
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| 35. |
- Karaye, Kamilu M., et al.
(författare)
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Clinical Features and Outcomes of Peripartum Cardiomyopathy in Nigeria
- 2020
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 76:20, s. 2352-2364
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Nigeria has the highest incidence of peripartum cardiomyopathy (PPCM) in the world. However, data on PPCM-related outcomes are limited. OBJECTIVES The purpose of this study was to examine the clinical profile, myocardial remodeling, and survival of patients with PPCM in Nigeria. METHODS This study consecutively recruited 244 PPCM patients (median 7 months postpartum) at 14 sites in Nigeria and applied structured follow-up for a median of 17 months (interquartile range: 14 to 20 months). Left ventricular reverse remodeling (LVRR) was defined as the composite of left ventricular (LV) end-diastolic dimension <33 mm/m(2) and absolute increase in left ventricular ejection fraction (LVEF) >= 10%. LV full recovery was defined as LVEF >= 55%. RESULTS Overall, 45 (18.7%) patients died during follow-up. Maternal age <20 years (hazard ratio [HR]: 2.40; 95% confidence interval (CI): 1.27 to 4.54), hypotension (HR: 1.87; 95% CI: 1.02 to 3.43), tachycardia (HR: 2.38; 95% CI: 1.05 to 5.43), and LVEF <25% at baseline (HR: 2.11; 95% CI: 1.12 to 3.95) independently predicted mortality. Obesity (HR: 0.16; 95% CI: 0.04 to 0.55) and regular use of beta-blockers at 6-month follow-up (HR: 0.20; 95% CI: 0.09 to 0.41) were independently associated with reduced risk for mortality. In total, 48 patients (24.1%) achieved LVRR and 45 (22.6%) achieved LV full recovery. LVEF <25% at baseline (HR: 0.66; 95% CI: 0.47 to 0.92) and regular use of beta-blockers at 6-month follow-up (HR: 1.62; 95% CI: 1.17 to 2.25) independently determined the risk for LV full recovery. Progressive reverse remodeling of all cardiac chambers was observed. In total, 18 patients (7.4%) were hospitalized during the study. CONCLUSIONS This is the largest study of PPCM in Africa. Consistent with late presentations, the mortality rate was high, whereas frequencies of LVRR and LV full recovery were low. Several variables predicted poor outcomes, and regular use of beta-blockers correlated with late survival and LV functional recovery. (C) 2020 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.
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| 36. |
- Kodra, Yllka, et al.
(författare)
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Recommendations for Improving the Quality of Rare Disease Registries
- 2018
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 15:8
-
Forskningsöversikt (refereegranskat)abstract
- Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.
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| 37. |
- Laine, Veronika N., et al.
(författare)
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Whole-genome Analysis Reveals Contrasting Relationships Among Nuclear and Mitochondrial Genomes Between Three Sympatric Bat Species
- 2023
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding mechanisms involved in speciation can be challenging, especially when hybridization or introgression blurs species boundaries. In bats, resolving relationships of some closely related groups has proved difficult due subtle interspecific variation both in morphometrics and molecular data sets. The endemic South American Histiotus bats, currently considered a subgenus of Eptesicus, harbor unresolved phylogenetic relationships and of those is a trio consisting of two closely related species: Eptesicus (Histiotus) macrotus and Eptesicus (Histiotus) montanus, and their relationship with a third, Eptesicus (Histiotus) magellanicus. The three sympatric species bear marked resemblance to each other, but can be differentiated morphologically. Furthermore, previous studies have been unable to differentiate the species from each other at a molecular level. In order to disentangle the phylogenetic relationships of these species, we examined the differentiation patterns and evolutionary history of the three Eptesicus (H.) species at the whole-genome level. The nuclear DNA statistics between the species suggest strong gene flow and recent hybridization between E. (H.) montanus and E. (H.) macrotus, whereas E. (H.) magellanicus shows a higher degree of isolation. In contrast, mitochondrial DNA shows a closer relationship between E. (H.) magellanicus and E. (H.) montanus. Opposing patterns in mtDNA and nuclear markers are often due to differences in dispersal, and here it could be both as a result of isolation in refugia during the last glacial maximum and female philopatry and male-biased dispersal. In conclusion, this study shows the importance of both the nuclear and mitochondrial DNA in resolving phylogenetic relationships and species histories.
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| 38. |
- Markljung, Ellen, et al.
(författare)
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ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth
- 2009
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:12, s. e1000256-
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Tidskriftsartikel (refereegranskat)abstract
- A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (ChIP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth.
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| 39. |
- Mullier, G.A., et al.
(författare)
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A search for the dimuon decay of the Standard Model Higgs boson with the ATLAS detector
- 2021
-
Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 812
-
Tidskriftsartikel (refereegranskat)abstract
- A search for the dimuon decay of the Standard Model (SM) Higgs boson is performed using data corresponding to an integrated luminosity of 139 fb−1 collected with the ATLAS detector in Run 2 pp collisions at s=13 TeV at the Large Hadron Collider. The observed (expected) significance over the background-only hypothesis for a Higgs boson with a mass of 125.09 GeV is 2.0σ (1.7σ). The observed upper limit on the cross section times branching ratio for pp→H→μμ is 2.2 times the SM prediction at 95% confidence level, while the expected limit on a H→μμ signal assuming the absence (presence) of a SM signal is 1.1 (2.0). The best-fit value of the signal strength parameter, defined as the ratio of the observed signal yield to the one expected in the SM, is μ=1.2±0.6. © 2020 The Author(s)
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| 40. |
- Mullier, G.A., et al.
(författare)
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Measurement of cross sections for production of a Z boson in association with a flavor-inclusive or doubly b-tagged large-radius jet in proton-proton collisions at Formula Presented with the ATLAS experiment
- 2023
-
Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 108:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present measurements of cross sections for production of a leptonically decaying Z boson in association with a large-radius jet in 13 TeV proton-proton collisions at the LHC, using 36 fb - 1 of data from the ATLAS detector. Integrated and differential cross sections are measured at particle level in both a flavor inclusive and a doubly b -tagged fiducial phase space. The large-radius jet mass and transverse momentum, its kinematic relationship to the Z boson, and the angular separation of b -tagged small-radius track jets within the large-radius jet are measured. This measurement constitutes an important test of perturbative quantum chromodynamics in kinematic and flavor configurations relevant to several Higgs boson and beyond-Standard-Model physics analyses. The results highlight issues with modeling of additional hadronic activity in the flavor-inclusive selection, and a distinction between flavor-number schemes in the b -tagged phase space. © 2023 CERN, for the ATLAS Collaboration.
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| 41. |
- Mullier, G.A., et al.
(författare)
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Measurement of the associated production of a Higgs boson decaying into b-quarks with a vector boson at high transverse momentum in pp collisions at s=13 TeV with the ATLAS detector
- 2021
-
Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 816
-
Tidskriftsartikel (refereegranskat)abstract
- The associated production of a Higgs boson with a W or Z boson decaying into leptons and where the Higgs boson decays to a bb¯ pair is measured in the high vector-boson transverse momentum regime, above 250 GeV, with the ATLAS detector. The analysed data, corresponding to an integrated luminosity of 139 fb−1, were collected in proton–proton collisions at the Large Hadron Collider between 2015 and 2018 at a centre-of-mass energy of s=13 TeV. The measured signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model, is 0.72−0.36 +0.39 corresponding to an observed (expected) significance of 2.1 (2.7) standard deviations. Cross-sections of associated production of a Higgs boson decaying into b quark pairs with a W or Z gauge boson, decaying into leptons, are measured in two exclusive vector boson transverse momentum regions, 250–400 GeV and above 400 GeV, and interpreted as constraints on anomalous couplings in the framework of a Standard Model effective field theory. © 2021 The Author
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| 42. |
- Mullier, G.A., et al.
(författare)
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Measurement of the top-quark mass using a leptonic invariant mass in pp collisions at √s = 13 TeV with the ATLAS detector
- 2023
-
Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media Deutschland GmbH. - 1029-8479 .- 1126-6708. ; 2023:6
-
Tidskriftsartikel (refereegranskat)abstract
- A measurement of the top-quark mass (mt) in the tt¯ → lepton + jets channel is presented, with an experimental technique which exploits semileptonic decays of b-hadrons produced in the top-quark decay chain. The distribution of the invariant mass mℓμ of the lepton, ℓ (with ℓ = e, μ), from the W-boson decay and the muon, μ, originating from the b-hadron decay is reconstructed, and a binned-template profile likelihood fit is performed to extract mt. The measurement is based on data corresponding to an integrated luminosity of 36.1 fb−1 of s = 13 TeV pp collisions provided by the Large Hadron Collider and recorded by the ATLAS detector. The measured value of the top-quark mass is mt = 174.41 ± 0.39 (stat.) ± 0.66 (syst.) ± 0.25 (recoil) GeV, where the third uncertainty arises from changing the Pythia8 parton shower gluon-recoil scheme, used in top-quark decays, to a recently developed setup. [Figure not available: see fulltext.]. © 2023, The Author(s).
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| 43. |
- Mullier, G.A., et al.
(författare)
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Measurements of jet observables sensitive to b -quark fragmentation in t t ¯ events at the LHC with the ATLAS detector
- 2022
-
Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 106:3
-
Tidskriftsartikel (refereegranskat)abstract
- Several observables sensitive to the fragmentation of b quarks into b hadrons are measured using 36 fb-1 of s=13 TeV proton-proton collision data collected with the ATLAS detector at the LHC. Jets containing b hadrons are obtained from a sample of dileptonic tt¯ events, and the associated set of charged-particle tracks is separated into those from the primary pp interaction vertex and those from the displaced b-decay secondary vertex. This division is used to construct observables that characterize the longitudinal and transverse momentum distributions of the b hadron within the jet. The measurements have been corrected for detector effects and provide a test of heavy-quark-fragmentation modeling at the LHC in a system where the top-quark decay products are color connected to the proton beam remnants. The unfolded distributions are compared with the predictions of several modern Monte Carlo parton-shower generators and generator tunes, and a wide range of agreement with the data is observed, with p values varying from 5×10-4 to 0.98. These measurements complement similar measurements from e+e- collider experiments in which the b quarks originate from a color singlet Z/γ∗. © 2022 CERN.
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| 44. |
- Mullier, G.A., et al.
(författare)
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Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at √s=13 TeV
- 2021
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 81:7
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 fb - 1 of pp collision data at s=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z→ μμ and J/ ψ→ μμ decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of | η| < 2.7. © 2021, CERN for the benefit of the ATLAS collaboration.
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| 45. |
- Mullier, G.A., et al.
(författare)
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Observation of photon-induced W+W− production in pp collisions at s=13 TeV using the ATLAS detector
- 2021
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 816
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Tidskriftsartikel (refereegranskat)abstract
- This letter reports the observation of photon-induced production of W-boson pairs, γγ→WW. The analysis uses 139 fb−1 of LHC proton–proton collision data taken at s=13 TeV recorded by the ATLAS experiment during the years 2015–2018. The measurement is performed selecting one electron and one muon, corresponding to the decay of the diboson system as WW→e±νμ∓ν final state. The background-only hypothesis is rejected with a significance of well above 5 standard deviations consistent with the expectation from Monte Carlo simulation. A cross section for the γγ→WW process of 3.13±0.31(stat.)±0.28(syst.) fb is measured in a fiducial volume close to the acceptance of the detector, by requiring an electron and a muon of opposite signs with large dilepton transverse momentum and exactly zero additional charged particles. This is found to be in agreement with the Standard Model prediction. © 2021 The Author(s)
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| 46. |
- Mullier, G.A., et al.
(författare)
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Search for charged-lepton-flavour violation in Z-boson decays with the ATLAS detector
- 2021
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 17:7, s. 819-825
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Tidskriftsartikel (refereegranskat)abstract
- Leptons with essentially the same properties apart from their mass are grouped into three families (or flavours). The number of leptons of each flavour is conserved in interactions, but this is not imposed by fundamental principles. Since the formulation of the standard model of particle physics, the observation of flavour oscillations among neutrinos has shown that lepton flavour is not conserved in neutrino weak interactions. So far, there has been no experimental evidence that this also occurs in interactions between charged leptons. Such an observation would be a sign of undiscovered particles or a yet unknown type of interaction. Here the ATLAS experiment at the Large Hadron Collider at CERN reports a constraint on lepton-flavour-violating effects in weak interactions, searching for Z-boson decays into a τ lepton and another lepton of different flavour with opposite electric charge. The branching fractions for these decays are measured to be less than 8.1 × 10−6 (eτ) and 9.5 × 10−6 (μτ) at the 95% confidence level using 139 fb−1 of proton–proton collision data at a centre-of-mass energy of s=13TeV and 20.3 fb−1 at s=8TeV. These results supersede the limits from the Large Electron–Positron Collider experiments conducted more than two decades ago. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 47. |
- Mullier, G.A., et al.
(författare)
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Search for squarks and gluinos in final states with jets and missing transverse momentum using 139 fb−1 of √s = 13 TeV pp collision data with the ATLAS detector
- 2021
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Ingår i: Journal of High Energy Physics. - : Springer Nature. - 1029-8479 .- 1126-6708. ; 2021:2
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Tidskriftsartikel (refereegranskat)abstract
- A search for the supersymmetric partners of quarks and gluons (squarks and gluinos) in final states containing jets and missing transverse momentum, but no electrons or muons, is presented. The data used in this search were recorded by the ATLAS experiment in proton-proton collisions at a centre-of-mass energy of s = 13 TeV during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. The results are interpreted in the context of various R-parity-conserving models where squarks and gluinos are produced in pairs or in association and a neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 2.30 TeV for a simplified model containing only a gluino and the lightest neutralino, assuming the latter is massless. For a simplified model involving the strong production of mass-degenerate first- and second-generation squarks, squark masses below 1.85 TeV are excluded if the lightest neutralino is massless. These limits extend substantially beyond the region of supersymmetric parameter space excluded previously by similar searches with the ATLAS detector. [Figure not available: see fulltext.] © 2021, The Author(s).
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| 48. |
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| 49. |
- Ohlin, Elisabet, et al.
(författare)
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Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.
- 2011
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 134, s. 2339-2357
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease.
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| 50. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)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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