| 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. |
- Ammanath, Aparna Viswanathan, et al.
(författare)
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From an Hsp90 - binding protein to a peptide drug.
- 2022
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Ingår i: microLife. - : Oxford University Press (OUP). - 2633-6693. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The Lpl proteins represent a class of lipoproteins that was first described in the opportunistic bacterial pathogen Staphylococcus aureus, where they contribute to pathogenicity by enhancing F-actin levels of host epithelial cells and thereby increasing S. aureus internalization. The model Lpl protein, Lpl1 was shown to interact with the human heat shock proteins Hsp90α and Hsp90ß, suggesting that this interaction may trigger all observed activities. Here we synthesized Lpl1-derived peptides of different lengths and identified two overlapping peptides, namely, L13 and L15, which interacted with Hsp90α. Unlike Lpl1, the two peptides not only decreased F-actin levels and S. aureus internalization in epithelial cells but they also decreased phagocytosis by human CD14+ monocytes. The well-known Hsp90 inhibitor, geldanamycin, showed a similar effect. The peptides not only interacted directly with Hsp90α, but also with the mother protein Lpl1. While L15 and L13 significantly decreased lethality of S. aureus bacteremia in an insect model, geldanamycin did not. In a mouse bacteremia model L15 was found to significantly decreased weight loss and lethality. Although the molecular bases of the L15 effect is still elusive, in vitro data indicate that simultaneous treatment of host immune cells with L15 or L13 and S. aureus significantly increase IL-6 production. L15 and L13 represent not antibiotics but they cause a significant reduction in virulence of multidrug-resistant S. aureus strains in in vivo models. In this capacity, they can be an important drug alone or additive with other agents.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Elhag, Sara, et al.
(författare)
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Differences in Cell-Intrinsic Inflammatory Programs of Yolk Sac and Bone Marrow Macrophages
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue-resident macrophages have mixed developmental origins. They derive in variable extent from yolk sac (YS) hematopoiesis during embryonic development. Bone marrow (BM) hematopoietic progenitors give rise to tissue macrophages in postnatal life, and their contribution increases upon organ injury. Since the phenotype and functions of macrophages are modulated by the tissue of residence, the impact of their origin and developmental paths has remained incompletely understood. Methods: In order to decipher cell-intrinsic macrophage programs, we immortalized hematopoietic progenitors from YS and BM using conditional HoxB8, and carried out an in-depth functional and molecular analysis of differentiated macrophages. Results: While YS and BM macrophages demonstrate close similarities in terms of cellular growth, differentiation, cell death susceptibility and phagocytic properties, they display differences in cell metabolism, expression of inflammatory markers and inflammasome activation. Reduced abundance of PYCARD (ASC) and CASPASE-1 proteins in YS macrophages abrogated interleukin-1 beta production in response to canonical and non-canonical inflammasome activation. Conclusions: Macrophage ontogeny is associated with distinct cellular programs and immune response. Our findings contribute to the understanding of the regulation and programming of macrophage functions.
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| 6. |
- 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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| 7. |
- Karmin, Monika, et al.
(författare)
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A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Pertold, Cino, et al.
(författare)
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Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014
- 2018
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Ingår i: Mammal Research. - : Springer Science and Business Media LLC. - 2199-2401 .- 2199-241X. ; 63:1
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Tidskriftsartikel (refereegranskat)abstract
- Harbor seals (Phoca vitulina) inhabit the seas surrounding Denmark and are an important top predator in the marine food chain. This trophic position exposes them to environmental contaminants with disease epi- demics and hunting being additional threats to this popu- lation. It is therefore important to study how environmen- tal pollution at the current order of magnitude affects the health of the population. Earlier studies have shown that occurrence of periodontitis could be linked to the amount of pollution the seals were subjected to. In order to inves- tigate this further, 380 skulls and 141 mandibles of harbor seals (Phoca vitulina) from the Wadden Sea, the Limfjord, and Kattegat collected during the period 1970–2014 were examined. The skulls were examined for pathological le- sions. The Hounsfield Units (HU) which are correlated to the bone mineral density (BMD) were measured in a sub- sample (n= 34) using CT scans. The macroscopic examination revealed (with the exception of the Swedish part of Kattegat) a significant increase of pathological lesions over the study period of 1981–2014. The exami- nation of HU showed that median HU measured at mul- tiple sites was highest in the healthy skulls compared to the skulls with one or more of the lesions. A discriminant analysis allowed high discriminatory capacity to separate healthy skulls from the skulls with pathologies, simply by the utilization of the HU data. Former studies of BMD in marine mammals have shown that exposure to environ- mental chemicals alter BMD and cause periodontitis. The present study, based on temporal and spatial trends in BMD, confirms the results of previous studies Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014 (PDF Download Available). Available from: https://www.researchgate.net/publication/320586176_Prevalence_of_skull_pathologies_in_European_harbor_seals_Phoca_vitulina_during_1981-2014 [accessed Dec 15 2017].
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