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- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 4. |
- Abrego, Nerea, et al.
(författare)
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Airborne DNA reveals predictable spatial and seasonal dynamics of fungi
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 631, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
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| 7. |
- Mizuno, T., et al.
(författare)
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High sensitivity balloon-borne hard X-ray/soft Gamma-Ray Polarimeter PoGOLite
- 2007
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Ingår i: Nuclear Science Symposium Conference Record, 2007. NSS ’07. IEEE. - : IEEE. - 9781424409228 ; , s. 2538-2544
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Konferensbidrag (refereegranskat)abstract
- The Polarized Gamma-ray Observer - Lightweight version (PoGOLite) is a new balloon experiment capable of detecting 10% polarization from a 200 mCrab source in the 25-80 keV energy range in a single 6-hour flight for the first time. Polarization measurements of hard X-rays and soft gamma-rays are expected to provide a powerful probe into high-energy emission mechanisms as well as source geometries. PoGOLite uses Compton scattering and photo-absorption to measure polarization in an array of 217 well-type phoswich detector cells made of plastic and BGO scintillators. The adoption of a well-type phoswich counter concept and a thick polyethylene neutron shield provides a narrow field-of-view (1.25 msr), a large effective area ( gt; 250 cm2 at 40-50 keV), a high modulation factor (more than 25%) and the low background ( 100 mCrab) required to conduct high-sensitivity polarization measurements. Through tests in laboratories and accelerator facilities of a scaled-down prototype with the front-end electronics of flight design and an extensive study by Monte Carlo simulation, we have demonstrated high instrument performance. PoGOLite will be ready for a first engineering flight in 2009 and a science flight in 2010, during which polarization signals from the Crab Nebula/pulsar, Cygnus X-1 and other objects will be observed.
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| 8. |
- Ovaskainen, Otso, et al.
(författare)
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Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
- 2024
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Ingår i: Scientific Data. - 2052-4463. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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| 9. |
- Savolainen, Vincent, et al.
(författare)
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Phylogeny of the eudicots : a nearly complete familial analysis based on rbcL gene sequences
- 2000
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Ingår i: Kew bulletin. - 0075-5974 .- 1874-933X. ; 55:2, s. 257-309
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Tidskriftsartikel (refereegranskat)abstract
- A phylogenetic analysis of 589 plastid rbcL gene sequences representing nearly all eudicot families (a total of 308 families; seven photosynthetic and four parasitic families are missing) was performed, and bootstrap re-sampling was used to assess support for clades. Based on these data, the ordinal classification of eudicots is revised following the previous classification of angiosperms by the Angiosperm Phylogeny Group (APG). Putative additional orders are discussed (e.g. Dilleniales, Escalloniales, Vitales), and several additional families are assigned to orders for future updates of the APG classification. The use of rbcL alone in such a large matrix was found to be practical in discovering and providing bootstrap support for most orders. Combination of these data with other matrices for the rest of the angiosperms should provide the framework for a complete phylogeny to be used in macro-evolutionary studies.
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| 10. |
- Takahashi, H., et al.
(författare)
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A thermal-neutron detector with a phoswich system of LiCaAlF6 and BGO crystal scintillators onboard PoGOLite
- 2010
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Ingår i: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference, NSS/MIC 2010 and 17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors, RTSD 2010. ; , s. 32-37
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Konferensbidrag (refereegranskat)abstract
- To measure the flux of atmospheric neutrons and study the neutron contribution to the background of the main detector of the PoGOLite (Polarized Gamma-ray Observer) balloon-borne experiment, a thermal-neutron detector with a phoswich system of LiCaAlF6 (Eu) and BGO crystal scintillators is developed. The performance to separate thermal-neutron events from those of gamma-rays and charged particles is validated with 252Cf on ground. The detector is attached to the PoGOLite instrument and is launched in 2011 from the Esrange facility in the North of Sweden. Although the emission wavelength of the LiCaAlF6 (Ce) is 300 nm and overlaps with the absorption wavelength of the BGO, the phoswich capability of the LiCaAlF6 (Ce) with the BGO is also confirmed with installing a waveform shifter.
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