| 1. |
- 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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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 4. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 5. |
- Liu, Daizhong, et al.
(författare)
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PHANGS–JWST First Results : Stellar-feedback-driven Excitation and Dissociation of Molecular Gas in the Starburst Ring of NGC 1365?
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- We compare embedded young massive star clusters (YMCs) to (sub-)millimeter line observations tracing the excitation and dissociation of molecular gas in the starburst ring of NGC 1365. This galaxy hosts one of the strongest nuclear starbursts and richest populations of YMCs within 20 Mpc. Here we combine near-/mid-IR PHANGS–JWST imaging with new Atacama Large Millimeter/submillimeter Array multi-J CO (1–0, 2–1 and 4–3) and [C ı] (1–0) mapping, which we use to trace CO excitation via R42 = ICO(4−3)/ICO(2−1) and R21 = ICO(2−1)/ICO(1−0) and dissociation via RCICO = I[CI](1−0)/ICO(2−1) at 330 pc resolution. We find that the gas flowing into the starburst ring from northeast to southwest appears strongly affected by stellar feedback, showing decreased excitation (lower R42) and increased signatures of dissociation (higher RCICO) in the downstream regions. There, radiative-transfer modeling suggests that the molecular gas density decreases and temperature and [CI/CO] abundance ratio increase. We compare R42 and RCICO with local conditions across the regions and find that both correlate with near-IR 2 μm emission tracing the YMCs and with both polycyclic aromatic hydrocarbon (11.3 μm) and dust continuum (21 μm) emission. In general, RCICO exhibits ∼0.1 dex tighter correlations than R42, suggesting C ı to be a more sensitive tracer of changing physical conditions in the NGC 1365 starburst than CO (4–3). Our results are consistent with a scenario where gas flows into the two arm regions along the bar, becomes condensed/shocked, forms YMCs, and then these YMCs heat and dissociate the gas.
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| 6. |
- Malbet, F., et al.
(författare)
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Faint objects in motion: the new frontier of high precision astrometry
- 2021
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:3, s. 845-886
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Tidskriftsartikel (refereegranskat)abstract
- Sky survey telescopes and powerful targeted telescopes play complementary roles in astronomy. In order to investigate the nature and characteristics of the motions of very faint objects, a flexibly-pointed instrument capable of high astrometric accuracy is an ideal complement to current astrometric surveys and a unique tool for precision astrophysics. Such a space-based mission will push the frontier of precision astrometry from evidence of Earth-mass habitable worlds around the nearest stars, to distant Milky Way objects, and out to the Local Group of galaxies. As we enter the era of the James Webb Space Telescope and the new ground-based, adaptive-optics-enabled giant telescopes, by obtaining these high precision measurements on key objects that Gaia could not reach, a mission that focuses on high precision astrometry science can consolidate our theoretical understanding of the local Universe, enable extrapolation of physical processes to remote redshifts, and derive a much more consistent picture of cosmological evolution and the likely fate of our cosmos. Already several missions have been proposed to address the science case of faint objects in motion using high precision astrometry missions: NEAT proposed for the ESA M3 opportunity, micro-NEAT for the S1 opportunity, and Theia for the M4 and M5 opportunities. Additional new mission configurations adapted with technological innovations could be envisioned to pursue accurate measurements of these extremely small motions. The goal of this White Paper is to address the fundamental science questions that are at stake when we focus on the motions of faint sky objects and to briefly review instrumentation and mission profiles.
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| 7. |
- Scheuermann, Fabian, et al.
(författare)
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Stellar associations powering H ii regions - I. Defining an evolutionary sequence
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 522:2, s. 2369-2383
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Tidskriftsartikel (refereegranskat)abstract
- Connecting the gas in H II regions to the underlying source of the ionizing radiation can help us constrain the physical processes of stellar feedback and how H II regions evolve over time. With PHANGS-MUSE, we detect nearly 24 000 H II regions across 19 galaxies and measure the physical properties of the ionized gas (e.g. metallicity, ionization parameter, and density). We use catalogues of multiscale stellar associations from PHANGS-HST to obtain constraints on the age of the ionizing sources. We construct a matched catalogue of 4177 H II regions that are clearly linked to a single ionizing association. A weak anticorrelation is observed between the association ages and the H a equi v alent width EW (H a), the H a/ FUV flux ratio, and the ionization parameter, log q . As all three are expected to decrease as the stellar population ages, this could indicate that we observe an evolutionary sequence. This interpretation is further supported by correlations between all three properties. Interpreting these as evolutionary tracers, we find younger nebulae to be more attenuated by dust and closer to giant molecular clouds, in line with recent models of feedback-regulated star formation. We also observe strong correlations with the local metallicity variations and all three proposed age tracers, suggestive of star formation preferentially occurring in locations of locally enhanced metallicity. Overall, EW (H a) and log q show the most consistent trends and appear to be most reliable tracers for the age of an H II region.
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| 8. |
- Thyssen, Jacob P., et al.
(författare)
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Effect of abrocitinib vs. dupilumab on skin pain : an analysis of the phase 3 JADE COMPARE and JADE DARE trials
- 2023
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Ingår i: British Journal of Dermatology. - : Oxford University Press. - 0007-0963 .- 1365-2133. ; 188:Suppl. 3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Skin pain is a common and bothersome symptom of atopic dermatitis (AD) that is associated with a substantial burden. To assess the efficacy of abrocitinib vs. dupilumab on skin pain in patients with moderate-to-severe AD. Data from patients aged ≥18 years who received oral abrocitinib 200 mg once daily (QD) or subcutaneous dupilumab 300 mg once every 2 weeks in combination with topical therapy in the phase 3 trials JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367) were analysed. Data from patients who received abrocitinib 100 mg QD or placebo in the JADE COMPARE trial were also included in this analysis. Patients rated their skin pain using the Skin Pain Numerical Rating Scale (NRS) item of the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) instrument [‘How painful was your skin over the past 24 h?’ on a scale from 0 (not painful) to 10 (extremely painful) ] in JADE COMPARE or the Skin Pain Numerical Rating Scale [SP-NRS, which queried patients for the severity of their ‘worst skin pain’ in the past 24 h on a scale from 0 (no skin pain) to 10 (worst skin pain imaginable)] in JADE DARE. Least squares mean (LSM) changes from baseline and proportions of patients who achieved a ≥4-point improvement from baseline in PSAAD skin pain score or SP-NRS were assessed through Week 16 (JADE COMPARE) or Week 26 (JADE DARE). The JADE COMPARE analysis (Skin Pain NRS item of the PSAAD) was performed post hoc, whereas the JADE DARE analysis (SP-NRS) was prespecified. At Week 2 of JADE COMPARE, LSM change from baseline in PSAAD skin pain score was greater with abrocitinib 200 mg [−2.8 (95% CI, −3.1, −2.5)] than with abrocitinib 100 mg [−2.1 (−2.3, −1.8)], dupilumab [−2.0 (−2.3, −1.8)], or placebo [−1.3 (−1.6, −0,9)]; improvements were sustained through Week 16 of treatment with abrocitinib 200 mg [−4.1 (−4.4, −3.8)], abrocitinib 100 mg [−3.3 (−3.6, −3.0)] and dupilumab [−4.0 (−4.2, −3.7)] compared with placebo [−1.8 (−2.2, −1.4)]. In JADE DARE, LSM change from baseline in SP-NRS was significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 [−3.7 (−3.9, −3.4) vs. −2.6 (−2.8, −2.3); P < 0.0001] and week 12 [−4.5 (−4.7, −4.2) vs. −4.0 (−4.3, −3.8); P = 0.0116]; no significant differences were observed between the treatment arms at Week 16 [−4.4 (−4.7, −4.2) vs. −4.2 (−4.4, −4.0); P = 0.16], Week 20 [−4.8 (−5.0, −4.5) vs. −4.5 (−4.7 vs. −4.2); P = 0.06] or Week 26 [−4.5 (−4.8, −4.3)] vs. −4.3 (−4.6, −4.1); P = 0.27]. The proportions of patients who achieved a ≥4-point improvement in PSAAD skin pain score at week 2 of JADE COMPARE were greater with abrocitinib 200 mg (43%) than with abrocitinib 100 mg (23%), dupilumab (24%) or placebo (14%). At Week 16, these proportions increased to 76% (abrocitinib 200 mg), 57% (abrocitinib 100 mg) and 70% (dupilumab) compared with placebo (29%). In JADE DARE, the proportions of patients who achieved a ≥4-point improvement in SP-NRS were significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 (58% vs. 36%; P < 0.0001) and Week 12 (71% vs. 61%; P = 0.0098) but not at subsequent timepoints. Similar to previous findings on the effect of abrocitinib on itch, these results suggest that abrocitinib 200 mg provides greater early skin pain relief in patients with moderate-to-severe AD compared with dupilumab, but the difference between the treatments diminishes with time. At earlier time points, skin pain improvement with abrocitinib 100 mg was similar to that with dupilumab.
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| 9. |
- Wec, Anna Z., et al.
(författare)
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Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington : National Academy of Science. - 0027-8424 .- 1091-6490. ; 117:12, s. 6675-6685
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive understanding of the development and evolution of human B cell responses duced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a gh-throughput single B cell cloning technology to longitudinally track the human B cell response to the llow fever virus 17D (YFV-17D) vaccine. The earlymemory B cell (MBC) response was mediated by both assical immunoglobulin M (IgM) (IgM(+)CD27(+)) and switched immunoglobulin (swIg(+)) MBC pulations; however, classical IgM MBCs waned rapidly, whereas swIg(+) and atypical IgM(+) and IgD(+) MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.
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