| 261. |
- Mascalzoni, Deborah, et al.
(författare)
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Comparison of participant information and informed consent forms of five European studies in genetic isolated populations
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:3, s. 296-302
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Tidskriftsartikel (refereegranskat)abstract
- Family-based research in genetically isolated populations is an effective approach for identifying loci influencing variation in disease traits. In common with all studies in humans, those in genetically isolated populations need ethical approval; however, existing ethical frameworks may be inadequate to protect participant privacy and confidentiality and to address participants' information needs in such populations. Using the ethical-legal guidelines of the Council for International Organizations of Medical Sciences (CIOMS) as a template, we compared the participant information leaflets and consent forms of studies in five European genetically isolated populations to identify additional information that should be incorporated into information leaflets and consent forms to guarantee satisfactorily informed consent. We highlight the additional information that participants require on the research purpose and the reasons why their population was chosen; on the potential risks and benefits of participation; on the opportunities for benefit sharing; on privacy; on the withdrawal of consent and on the disclosure of genetic data. This research raises some important issues that should be addressed properly and identifies relevant types of information that should be incorporated into information leaflets for this type of study.
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| 262. |
- Orgel, Csilla, et al.
(författare)
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Gridmapping the Northern Plains of Mars: A New Overview of Recent Water‐ and Ice‐Related Landforms in Acidalia Planitia.
- 2019
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9100. ; 124:2, s. 454-82
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Tidskriftsartikel (refereegranskat)abstract
- We used a grid‐mapping technique to analyze the distribution of 13 water‐ and ice‐related landforms in Acidalia Planitia as part of a joint effort to study the three main basins in the northern lowlands of Mars, that is, Acidalia, Utopia, and Arcadia Planitiae. The landforms were mapped at full Context Camera resolution along a 300‐km‐wide strip from 20°N to 84°N. We identified four landform assemblages: (1) Geologically recent polar cap (massive ice), which superposes the latitude‐dependent mantle (LDM) (LA1); (2) ice‐related landforms, such as LDM, textured terrain, small‐scale polygons, scalloped terrain, large‐scale viscous flow features, and gullies, which have an overlapping distribution (LA2); (3) surface features possibly related to water and subsurface sediment mobilization (LA3; kilometer‐scale polygons, large pitted mounds, small pitted mounds, thumbprint terrain); and (4) irregularly shaped pits with raised rims on equator‐facing slopes. Pits are likely the result of an energetic release of volatiles (H2O, CO2, and CH4), rather than impact‐, volcanism‐, or wind‐related processes. LDM occurs ubiquitously from 44°N to 78°N in Acidalia Planitia. Various observations suggest an origin of air fall deposition of LDM, which contains less ice in the uppermost tens of meters in Acidalia Planitia than in Arcadia and Utopia Planitiae. However, LDM may be thicker and more extended in the past in Acidalia Planitia. The transition between LDM‐free terrain and LDM is situated further north than in Utopia and Arcadia Planitiae, suggesting different past and/or present climatic conditions among the main basins in the northern lowlands.
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| 263. |
- O’Sullivan, John F., et al.
(författare)
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Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes
- 2017
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 127:12, s. 4394-4402
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Tidskriftsartikel (refereegranskat)abstract
- Unbiased, “nontargeted” metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CT-defined nonalcoholic fatty liver disease (NAFLD) in the offspring cohort of the Framingham Heart Study (FHS) participants. We verified the relationship between DMGV and early hepatic pathology. Specifically, plasma DMGV levels were correlated with biopsy-proven nonalcoholic steatohepatitis (NASH) in a hospital cohort of individuals undergoing gastric bypass surgery, and DMGV levels fell in parallel with improvements in post-procedure cardiometabolic parameters. Further, baseline DMGV levels independently predicted future diabetes up to 12 years before disease onset in 3 distinct human cohorts. Finally, we provide all metabolite peak data consisting of known and unidentified peaks, genetics, and key metabolic parameters as a publicly available resource for investigations in cardiometabolic diseases.
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| 264. |
- Rossi, Matteo, et al.
(författare)
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Resonant inelastic X-ray scattering of magnetic excitations under pressure
- 2019
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 26, s. 1725-1732
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Tidskriftsartikel (refereegranskat)abstract
- Resonant inelastic X-ray scattering (RIXS) is an extremely valuable tool for the study of elementary, including magnetic, excitations in matter. The latest developments of this technique have mostly been aimed at improving the energy resolution and performing polarization analysis of the scattered radiation, with a great impact on the interpretation and applicability of RIXS. Instead, this article focuses on the sample environment and presents a setup for high-pressure low-temperature RIXS measurements of low-energy excitations. The feasibility of these experiments is proved by probing the magnetic excitations of the bilayer iridate Sr 3 Ir 2 O 7 at pressures up to 12 GPa.
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| 265. |
- Sánchez-Cano, Beatriz, et al.
(författare)
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Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
- 2023
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8
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Tidskriftsartikel (refereegranskat)abstract
- Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
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| 266. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 267. |
- Smedby, Karin E., et al.
(författare)
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GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:4, s. e1001378-
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, P-combined= 2x10(-21)) located 962 bp away from rs10484561 (r(2)< 0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012: ORadjusted = 0.70, P-adjusted= 4x10(-12); rs10484561: ORadjusted = 1.64, P-adjusted= 5x10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, P-combined = 1.4x10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
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| 268. |
- Štambuk, Jerko, et al.
(författare)
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Global variability of the human IgG glycome
- 2020
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589. ; 12:15, s. 15222-15259
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.
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| 269. |
- Surakka, Ida, et al.
(författare)
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A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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| 270. |
- Testor, Pierre, et al.
(författare)
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OceanGliders: A component of the integrated GOOS
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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