| 1. |
- 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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| 2. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 3. |
- Artaxo, Paulo, et al.
(författare)
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Tropical and Boreal Forest – Atmosphere Interactions : A Review
- 2022
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 74:1, s. 24-163
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Forskningsöversikt (refereegranskat)abstract
- This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiäla in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.
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| 4. |
- Binder, Zev A., et al.
(författare)
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Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
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Tidskriftsartikel (refereegranskat)abstract
- We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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| 5. |
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| 6. |
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| 7. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 8. |
- Divé, Iris, et al.
(författare)
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Tick-borne encephalitis virus (TBEV) infection in pregnancy: Absence of virus transmission to the fetuses despite severe maternal disease - A case study.
- 2020
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Ingår i: Ticks and tick-borne diseases. - : Elsevier BV. - 1877-9603 .- 1877-959X. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is an emerging infectious disease in large parts of Europe and Asia. Whereas other members of the Flaviviridae family can harm fetal development, there are only very few reports on TBE virus (TBEV) infections during pregnancy. Thus, the implications for fetal health remain largely unknown. In this study, we present detailed pre- and postnatal health assessment of three children in the context of severe maternal TBEV infection during pregnancy. Following acute TBEV infection of the mothers, intrauterine growth and development of all children were assessed by repetitive prenatal ultrasound. Postnatal examinations included clinical and virological analyses over a follow-up period of 18 months. Prenatally, no signs of intrauterine growth restrictions were observed. All neonates were delivered at term. Umbilical cord blood of the newborns tested negative for TBEV RNA. Virus-specific IgG antibodies were positive at birth but negative at 9 and 11 months of age. Importantly, IgM antibodies remained negative throughout the period of observation. Taken together, these clinical and virological data strongly suggest that fetal TBEV infection did not occur, despite severe manifestations in the mothers.
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| 9. |
- Kaidar-Person, Orit, et al.
(författare)
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The Lucerne Toolbox 2 to optimise axillary management for early breast cancer : a multidisciplinary expert consensus
- 2023
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Ingår i: EClinicalMedicine. - 2589-5370. ; 61
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Forskningsöversikt (refereegranskat)abstract
- Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the “Lucerne Toolbox”, a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients’ journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%–74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.
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| 10. |
- Mahler, Jasmin, et al.
(författare)
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Endogenous murine A beta increases amyloid deposition in APP23 but not in APPPS1 transgenic mice
- 2015
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 36:7, s. 2241-2247
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous murine amyloid-beta peptide (A beta) is expressed in most A beta precursor protein (APP) transgenic mouse models of Alzheimers disease but its contribution to beta-amyloidosis remains unclear. We demonstrate similar to 35% increased cerebral A beta load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster A beta-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine A beta, and immunoelectron microscopy revealed a tight association of murine A beta with human A beta fibrils. Deposition of murine A beta was considerably less efficient compared with the deposition of human A beta indicating a lower amyloidogenic potential of murine A beta in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human A beta and deposits of mixed human-murine A beta. Our data demonstrate a differential effect of murine A beta on human A beta deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse A beta may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.
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| 11. |
- Marton, Janos, et al.
(författare)
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NMR Analysis of a Series of 6,14-Ethenomorphinan Derivatives as PET Precursors and Reference Substances**
- 2021
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Ingår i: ChemistrySelect. - : Wiley. - 2365-6549. ; 6:24, s. 5994-6005
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Tidskriftsartikel (refereegranskat)abstract
- The new semisynthetic oripavine derivative 3-O-trityl-6-O-desmethyl-dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six-step procedure. This compound can be applied as precursor for the radiosynthesis of [6-O-methyl-C-11]-dihydroetorphine ([C-11]DHE). We present a detailed description of H-1 and C-13 NMR data of reference standards and precursors for [6-O-methyl-C-11]- and [6-O-(2-[F-18]fluoroethyl]orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3-O-trityl-6-O-desmethyl-phenethyl-orvinol (TDPEO) using computational methods.
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| 12. |
- Milisavljevic, Dan, et al.
(författare)
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A JWST Survey of the Supernova Remnant Cassiopeia A
- 2024
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 965:2
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Tidskriftsartikel (refereegranskat)abstract
- We present initial results from a James Webb Space Telescope (JWST) survey of the youngest Galactic core-collapse supernova remnant, Cassiopeia A (Cas A), made up of NIRCam and MIRI imaging mosaics that map emission from the main shell, interior, and surrounding circumstellar/interstellar material (CSM/ISM). We also present four exploratory positions of MIRI Medium Resolution Spectrograph integral field unit spectroscopy that sample ejecta, CSM, and associated dust from representative shocked and unshocked regions. Surprising discoveries include (1) a weblike network of unshocked ejecta filaments resolved to ∼0.01 pc scales exhibiting an overall morphology consistent with turbulent mixing of cool, low-entropy matter from the progenitor's oxygen layer with hot, high-entropy matter heated by neutrino interactions and radioactivity; (2) a thick sheet of dust-dominated emission from shocked CSM seen in projection toward the remnant's interior pockmarked with small (∼1'') round holes formed by ≲01 knots of high-velocity ejecta that have pierced through the CSM and driven expanding tangential shocks; and (3) dozens of light echoes with angular sizes between ∼01 and 1' reflecting previously unseen fine-scale structure in the ISM. NIRCam observations place new upper limits on infrared emission (≲20 nJy at 3 μm) from the neutron star in Cas A's center and tightly constrain scenarios involving a possible fallback disk. These JWST survey data and initial findings help address unresolved questions about massive star explosions that have broad implications for the formation and evolution of stellar populations, the metal and dust enrichment of galaxies, and the origin of compact remnant objects.
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| 13. |
- Nevens, Frederik, et al.
(författare)
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A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 375:7, s. 631-43
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Tidskriftsartikel (refereegranskat)abstract
- Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.
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| 14. |
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| 15. |
- Patade, Sachin, et al.
(författare)
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Empirical formulation for multiple groups of primary biological ice nucleating particles from field observations over Amazonia
- 2021
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Ingår i: Journal of the Atmospheric Sciences. - 1520-0469. ; 78, s. 2195-2220
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Tidskriftsartikel (refereegranskat)abstract
- To resolve the various types of biological ice nuclei (IN) with atmospheric models, an extension of the empirical parameterization (EP) is proposed to predict the active IN from multiple groups of primary biological aerosol particles (PBAPs). Our approach is to utilize coincident observations of PBAP sizes, concentrations, biological composition, and ice nucleating ability. The parameterization organizes PBAPs into five basic groups: 1) fungal spores, 2) bacteria, 3) pollen, 4) viral particles, plant/animal detritus, 5) algae, and their respective fragments. This new biological component of the EP was constructed by fitting predicted concentrations of PBAP IN to those observed at the Amazon Tall Tower Observatory (ATTO) site located in the central Amazon. The fitting parameters for pollen and viral particles and plant/animal detritus, which are much less active as IN than fungal and bacterial groups, are constrained based on their ice nucleation activity from the literature. The parameterization has empirically derived dependencies on the surface area of each group (except algae), and the effects of variability in their mean sizes and number concentrations are represented via their influences on surface area. The concentration of active algal IN is estimated from literature-based measurements. Predictions of this new biological component of the EP are consistent with previous laboratory and field observations not used in its construction. The EP scheme was implemented in a 0D parcel model. It confirms that biological IN account for most of the total IN activation at temperatures warmer than −20°C and at colder temperatures dust and soot become increasingly more important to ice nucleation.
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| 16. |
- Persson, Roger, et al.
(författare)
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Synthesis, Characterization, and Novel Fluxional Mechanisms of Triosmium Clusters Containing the Highly Flexible Ligand Ph2PC2H4SC2H4SC2H4PPh2 (PSSP)
- 2010
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 1520-6041 .- 0276-7333. ; 29:10, s. 2223-2233
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of Ph2PC2H4SC2H4SC2H4PPh2 (PSSP) with [Os-3(CO)(11)(NCMe)] under mild conditions yields [{Os-3(CO)(11)}(2)(mu-PSSP)], 1, and [Os-3(CO)(11)(PSSP)], 2. In cluster 1 the ligand links two trinuelear cluster subunits, coordinating via its phosphine moieties. In cluster 2, the ligand is coordinated through one of the phosphine groups, while the remaining part of the PSSP ligand is oriented in a dangling mode. Treatment of [Os-3(CO)(11)(NCMe)(2)] with PSSP yields 1,2-[Os-3(CO)(10)(PSSP)], 3. NMR data presented in this paper indicate that a concerted cis/trans isomerism with respect to the phosphines operates in the cluster. This type of process has not been observed previously for a bridging ligand, but has been detected in the case of corresponding triosmium clusters with bis-monodentate phosphine ligands. Oxidative decarbonylation of [{Os-3(CO)(11)}(2)(mu-PSSP)], 1, with Me3NO yields cluster [{Os-3(CO)(10)}(2)(mu-PSSP)], 4. This cluster consists of two P,S-bridged cluster units. In solution at room temperature, 4 undergoes a slow rearrangement from a 1,2-bridging to a 1,1-chelating coordination mode. The crystal structures of clusters 1, 3, and 4 are reported.
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| 17. |
- Ruggeri, Kai, et al.
(författare)
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The general fault in our fault lines
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 5:10, s. 1369-1380
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Tidskriftsartikel (refereegranskat)abstract
- Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.
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| 18. |
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| 19. |
- San-Jose, Luis M., et al.
(författare)
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Differential fitness effects of moonlight on plumage colour morphs in barn owls
- 2019
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Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 3:9, s. 1331-1340
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Tidskriftsartikel (refereegranskat)abstract
- The Moon cycle exposes nocturnal life to variation in environmental light. However, whether moonlight shapes the fitness of nocturnal species with distinct colour variants remains unknown. Combining data from long-term monitoring, high-resolution global positioning system tracking and experiments using prey, we show that barn owls (Tyto alba) with distinct plumage colourations are differently affected by moonlight. The reddest owls are less successful at hunting and providing food to their offspring during moonlit nights, which associates with lower body mass and lower survival of the youngest nestlings and with female mates starting to lay eggs at low moonlight levels. Although moonlight should make white owls more conspicuous to prey, it either positively affects or does not affect the hunting and fitness of the whitest owls. We experimentally show that, under full-moon conditions, white plumage triggers longer freezing times in prey, which should facilitate prey catchability. We propose that the barn owl’s white plumage, a rare trait among nocturnal predators, exploits the known aversion of rodents to bright light, explaining why, counterintuitively, moonlight has a lesser impact on the whitest owls. Our study provides evidence for the long-suspected influence of the Moon on the evolution of colouration in nocturnal species, highlighting the importance of colour in nocturnal ecosystems.
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| 20. |
- Sanchez, Sophie, et al.
(författare)
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3D Microstructural Architecture of Muscle Attachments in Extant and Fossil Vertebrates Revealed by Synchrotron Microtomography
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e56992-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Firm attachments binding muscles to skeleton are crucial mechanical components of the vertebrate body. These attachments (entheses) are complex three-dimensional structures, containing distinctive arrangements of cells and fibre systems embedded in the bone, which can be modified during ontogeny. Until recently it has only been possible to obtain 2D surface and thin section images of entheses, leaving their 3D histology largely unstudied except by extrapolation from 2D data. Entheses are frequently preserved in fossil bones, but sectioning is inappropriate for rare or unique fossil material.Methodology/Principal Findings: Here we present the first non-destructive 3D investigation, by propagation phase contrast synchrotron microtomography (PPC-SR mu CT), of enthesis histology in extant and fossil vertebrates. We are able to identify entheses in the humerus of the salamander Desmognathus from the organization of bone-cell lacunae and extrinsic fibres. Statistical analysis of the lacunae differentiates types of attachments, and the orientation of the fibres, reflect the approximate alignment of the muscle. Similar histological structures, including ontogenetically related pattern changes, are perfectly preserved in two 380 million year old fossil vertebrates, the placoderm Compagopiscis croucheri and the sarcopterygian fish Eusthenopteron foordi.Conclusions/Significance: We are able to determine the position of entheses in fossil vertebrates, the approximate orientation of the attached muscles, and aspects of their ontogenetic histories, from PPC-SRmCT data. Sub-micron microtomography thus provides a powerful tool for studying the structure, development, evolution and palaeobiology of muscle attachments.
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| 21. |
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| 22. |
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| 23. |
- Schmidt, Peter Paul, et al.
(författare)
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Kinetic evidence that a radical transfer pathway in protein R2 of mouse ribonucleotide reductase is involved in generation of the tyrosyl free radical
- 1998
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 273:34, s. 21463-21472
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Tidskriftsartikel (refereegranskat)abstract
- Class I ribonucleotide reductases consist of two subunits, R1 and R2. The active site is located in R1; active R2 contains a diferric center and a tyrosyl free radical (Tyr()), both essential for enzymatic activity. The proposed mechanism for the enzymatic reaction includes the transport of a reducing equivalent, i.e. electron or hydrogen radical, across a 35-Å distance between Tyr() in R2 and the active site in R1, which are connected by a hydrogen-bonded chain of conserved, catalytically essential amino acid residues. Asp266 and Trp103 in mouse R2 are part of this radical transfer pathway. The diferric/Tyr() site in R2 is reconstituted spontaneously by mixing iron-free apoR2 with Fe(II) and O2. The reconstitution reaction requires the delivery of an external reducing equivalent to form the diferric/Tyr() site. Reconstitution kinetics were investigated in mouse apo-wild type R2 and the three mutants D266A, W103Y, and W103F by rapid freeze-quench electron paramagnetic resonance with ≤4 Fe(II)/R2 at various reaction temperatures. The kinetics of Tyr() formation in D266A and W103Y is on average 20 times slower than in wild type R2. More strikingly, Tyr() formation is completely suppressed in W103F. No change in the reconstitution kinetics was found starting from Fe(II)-preloaded proteins, which shows that the mutations do not affect the rate of iron binding. Our results are consistent with a reaction mechanism using Asp266 and Trp103 for delivery of the external reducing equivalent. Further, the results with W103F suggest that an intact hydrogen-bonded chain is crucial for the reaction, indicating that the external reducing equivalent is a H(). Finally, the formation of Tyr() is not the slowest step of the reaction as it is in Escherichia coli R2, consistent with a stronger interaction between Tyr() and the iron center in mouse R2. A new electron paramagnetic resonance visible intermediate named mouse X, strikingly similar to species X found in E. coli R2, was detected only in small amounts under certain conditions. We propose that it may be an intermediate in a side reaction leading to a diferric center without forming the neighboring Tyr().
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| 24. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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