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- 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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- Lillethorup, Thea Pinholt, et al.
(författare)
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In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
- 2018
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Ingår i: Synapse. - : Wiley. - 0887-4476. ; 72:12
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
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- Steele, G., et al.
(författare)
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Absorption of blocking activity from human tumor‐bearer sera by staphylococcus aureus, cowan I
- 1975
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 15:2, s. 180-189
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus, strain Cowan I, contains a cell‐wall substance, protein A, which combines with the Fc part of IgG in most mammalian species. It can therefore be used as a solid‐phase immunoabsorbant for elimination of the reacting immunoglobulins. Since it has been shown that Cowan I could absorb out the blocking activity of sera from rats bearing isografts of polyoma‐virus‐induced sarcomas or chemically induced colon carcinomas, we investigated what effects Cowan I absorption of human tumor‐bearer sera might have. In all tumor‐bearer sera tested, from patients with melanomas or colon carcinomas, treatment with protein‐A‐containing staphylococci decreased the sera's ability to inhibit lymphocyte‐mediated cytotoxicity in vitro. Cowan‐I‐treated sera from healthy controls had no effect on lymphocyte cytotoxicity. Nor did Cowan‐I‐treated tumor‐bearer sera potentiate or „arm” normal lymphocytes against tumor target cells. There was no evidence of complement‐dependent cytotoxicity with added human complement in sera from melanoma and colon carcinoma bearing patients either before or after absorption with Staphylococcus aureus, Cowan I. The concentrations of IgA, IgG and IgM were determined in sera used for in vitro tests of blocking activity and complement‐dependent cytotoxicity before and after absorption. No reduction of IgA, reduction to undetectable levels of IgG and 20–30% reduction of IgM immunoglobulins as compared to unabsorbed sera were demonstrated.
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- 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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