| 1. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :11
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Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 6. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 7. |
- Prieto-Díaz, Rubén, et al.
(author)
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Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists
- 2023
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:1, s. 890-912
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Journal article (peer-reviewed)abstract
- The modulation of the A2B adenosine receptor is a promising strategy in cancer (immuno) therapy, with A2BAR antagonists emerging as immune checkpoint inhibitors. Herein, we report a systematic assessment of the impact of (di- and mono-)halogenation at positions 7 and/or 8 on both A2BAR affinity and pharmacokinetic properties of a collection of A2BAR antagonists and its study with structure-based free energy perturbation simulations. Monohalogenation at position 8 produced potent A2BAR ligands irrespective of the nature of the halogen. In contrast, halogenation at position 7 and dihalogenation produced a halogen-size-dependent decay in affinity. Eight novel A2BAR ligands exhibited remarkable affinity (Ki < 10 nM), exquisite subtype selectivity, and enantioselective recognition, with some eutomers eliciting sub-nanomolar affinity. The pharmacokinetic profile of representative derivatives showed enhanced solubility and microsomal stability. Finally, two compounds showed the capacity of reversing the antiproliferative effect of adenosine in activated primary human peripheral blood mononuclear cells.
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| 8. |
- Rodriguez-Espigares, Ismael, et al.
(author)
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GPCRmd uncovers the dynamics of the 3D-GPCRome
- 2020
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In: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 17:8, s. 777-787
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Journal article (peer-reviewed)abstract
- G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
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| 9. |
- Rueda, Blanca, et al.
(author)
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Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis
- 2006
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3815-3819
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Recent findings suggest that interferon regulatory factor 5 (IRF-5) may play a crucial role in several cellular processes, including the transcription of genes for inflammatory cytokines. Two genetic variants of the IRF5 gene (rs2004640 in exon 1 and rs2280714 in the 3'-untranslated region) have been shown to exert functional modifications affecting IRF5 messenger RNA splicing and expression, and have been associated with genetic predisposition to systemic lupus erythematosus (SLE). The aim of this study was to analyze the possible contribution of the IRF5 gene to the predisposition to rheumatoid arthritis (RA). METHODS: Three case-control cohorts from Spain (724 RA patients and 542 healthy controls), Sweden (281 RA patients 474 healthy controls), and Argentina (284 RA patients and 286 healthy controls) were independently analyzed. Genotyping for IRF5 rs2004640 and rs2280714 was performed using a TaqMan 5' allele-discrimination assay. RESULTS: In the 3 cohorts studied, no statistically significant differences in allele or genotype frequencies of the rs2004640 and rs2280714 IRF5 polymorphisms were observed between RA patients and controls. Accordingly, haplotype analysis revealed that none of the IRF5 haplotypes was associated with genetic predisposition to RA. CONCLUSION: Our results suggest that the IRF5 functional polymorphisms analyzed do not seem to be implicated in genetic susceptibility to RA.
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| 10. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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