| 1. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 2. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 3. |
- Rasmussen, Simon, et al.
(författare)
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Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago
- 2015
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Ingår i: Cell. - : Elsevier. - 0092-8674. ; 163:3, s. 571-582
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Tidskriftsartikel (refereegranskat)abstract
- The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence ofgenetic changes that lead to increased virulenceand the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.
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| 4. |
- Björkman, Anne, 1981, et al.
(författare)
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Plant functional trait change across a warming tundra biome
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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| 5. |
- Björkman, Anne, 1981, et al.
(författare)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 6. |
- Irving-Pease, Evan K., et al.
(författare)
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The selection landscape and genetic legacy of ancient Eurasians
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 312-320
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Tidskriftsartikel (refereegranskat)abstract
- The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes 1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.
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| 7. |
- Nielsen, Simon D., et al.
(författare)
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A highly selective agonist for the metabotropic glutamate receptor mGluR2
- 2011
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Ingår i: MedChemComm. ; 2:1, s. 1120-1124
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Tidskriftsartikel (refereegranskat)abstract
- The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H2O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.
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| 8. |
- Rypdal, Veronika, et al.
(författare)
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Uveitis in Juvenile Idiopathic Arthritis : 18-Year Outcome in the Population-based Nordic Cohort Study
- 2021
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Ingår i: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 128:4, s. 598-608
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA).Design: Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA.Participants: A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden.Methods: Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data.Main Outcome Measures: Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications.Results: Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1 %]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12.Conclusions: Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.
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| 9. |
- Barrie, William, et al.
(författare)
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Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 625:7994
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment. Analysis of a large ancient genome dataset shows that genetic risk for multiple sclerosis rose in steppe pastoralists, providing insight into how genetic ancestry from the Neolithic and Bronze Age has shaped modern immune responses.
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| 10. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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