| 1. |
- Scepanovic, Petar, et al.
(författare)
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Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines
- 2018
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Humoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that human genetic variation influences (i) serum immunoglobulin levels, (ii) seroconversion rates, and (iii) intensity of antigen-specific immune responses. Here, we evaluated the impact of intrinsic (age and sex), environmental, and genetic factors on the variability of humoral response to common pathogens and vaccines. Methods: We characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age- and sex-stratified cohort of 1000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG, and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~5 million genetic variants and antibody responses using single marker and gene burden tests. Results: We identified age and sex as important determinants of humoral immunity, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leukocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations. Conclusions: Using extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrated that age, sex, and specific human genetic variants contribute to inter-individual variability in humoral immunity. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis.
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| 2. |
- Balkenius, Christian, et al.
(författare)
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Elements of cognition for general intelligence
- 2023
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Ingår i: Artificial General Intelligence : 16th International Conference, AGI 2023, Stockholm, Sweden, June 16–19, 2023, Proceedings - 16th International Conference, AGI 2023, Stockholm, Sweden, June 16–19, 2023, Proceedings. - 0302-9743 .- 2945-9141 .- 1611-3349 .- 2945-9133. - 9783031334689 - 9783031334696 ; 13921, s. 11-20
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Konferensbidrag (refereegranskat)abstract
- What can artificial intelligence learn from the cognitive sciences? We review some fundamental aspects of how human cognition works and relate it to different brain structures and their function. A central theme is that cognition is very different from how it is envisioned in classical artificial intelligence which offers a novel path toward intelligent systems that in many ways is both simpler and more attainable. We also argue that artificial intelligent systems takes more than a single silver bullet. It requires a large number of interacting subsystem that are coupled to both the body and to the environment. We argue for an approach to artificial general intelligence based on a faithful reproduction of known brain processes in a system-level model that incorporates a large number of components modelled after the human brain.
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| 3. |
- Bergamaschi, Peter, et al.
(författare)
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European Obspack compilation of atmospheric carbon dioxide data from ICOS and non-ICOS European stations for the period 1972-2023; : obspack_co2_466_GLOBALVIEWplus_v8.0_2023-04-26
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This data package contains high accuracy CO2 dry air mole fractions from 58 ICOS and non-ICOS European observatories at in total 132 observation levels, collected by the ICOS Atmosphere Thematic Centre (ATC) and provided by the station contributors. The package is part of the Globalviewplus v8.0 data product, released in 2022 and is intended for use in carbon cycle inverse modeling, model evaluation, and satellite validation studies. Please report errors and send comments regarding this product to the ObsPack originators. Please read carefully the ObsPack Fair Use statement and cite appropriately. This is the sixth release of the GLOBALVIEWplus (GV+) cooperative data product. Please review the release notes for this product at www.esrl.noaa.gov/gmd/ccgg/obspack/release_notes.html. Metadata for this product are available at https://commons.datacite.org/doi.org/10.18160/CEC4-CAGK. Please visit http://www.gml.noaa.gov/ccgg/obspack/ for more information.
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| 4. |
- Heiskanen, Jouni, et al.
(författare)
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The Integrated Carbon Observation System in Europe
- 2022
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 103:3, s. 855-872
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Tidskriftsartikel (refereegranskat)abstract
- Since 1750, land-use change and fossil fuel combustion has led to a 46% increase in the atmospheric carbon dioxide (CO2) concentrations, causing global warming with substantial societal consequences. The Paris Agreement aims to limit global temperature increases to well below 2C above preindustrial levels. Increasing levels of CO2 and other greenhouse gases (GHGs), such as methane (CH4) and nitrous oxide (N2O), in the atmosphere are the primary cause of climate change. Approximately half of the carbon emissions to the atmosphere are sequestered by ocean and land sinks, leading to ocean acidification but also slowing the rate of global warming. However, there are significant uncertainties in the future global warming scenarios due to uncertainties in the size, nature, and stability of these sinks. Quantifying and monitoring the size and timing of natural sinks and the impact of climate change on ecosystems are important information to guide policy-makers' decisions and strategies on reductions in emissions. Continuous, long-term observations are required to quantify GHG emissions, sinks, and their impacts on Earth systems. The Integrated Carbon Observation System (ICOS) was designed as the European in situ observation and information system to support science and society in their efforts to mitigate climate change. It provides standardized and open data currently from over 140 measurement stations across 12 European countries. The stations observe GHG concentrations in the atmosphere and carbon and GHG fluxes between the atmosphere, land surface, and the oceans. This article describes how ICOS fulfills its mission to harmonize these observations, ensure the related long-term financial commitments, provide easy access to well-documented and reproducible high-quality data and related protocols and tools for scientific studies, and deliver information and GHG-related products to stakeholders in society and policy.
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| 5. |
- Papale, Dario, et al.
(författare)
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Standards and Open Access are the ICOS Pillars Reply to "Comments on 'The Integrated Carbon Observation System in Europe'"
- 2023
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 104:12, s. 953-955
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Tidskriftsartikel (refereegranskat)abstract
- In his comment (Kowalski 2023) on our recent publication (Heiskanen et al. 2022) where we present the Integrated Carbon Observation System (ICOS) research infrastructure, Andrew Kowalski introduces three important and, in our opinion, different potential issues in the definition, collection, and availability of field measurements made by the ICOS network, and he proposes possible solutions to these issues.
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| 6. |
- Patin, Etienne, et al.
(författare)
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Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
- 2018
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 19, s. 302-314
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Tidskriftsartikel (refereegranskat)abstract
- The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.
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| 7. |
- Scepanovic, Petar, et al.
(författare)
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A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals
- 2019
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. RESULTS: Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. CONCLUSION: In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01699893.
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