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Western Eurasia witnessed several large-scale human migrations during the Holocene 1-5 . 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., (© 2024. The Author(s).)

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales 1-4 . However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution 5-7 . 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 ( 13 C and 15 N content), mobility ( 87 Sr/ 86 Sr 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., (© 2024. The Author(s).)

We have reported that single doses of alcohol diminish total sialic acid in rat brain. Recent results indicate that this effect seems to be largely accounted for by alcohol-induced reduction in gangliosides. In these experiments, five replicate groups of mice were injected IP with a single dose of 20% alcohol and saline as control. At 1 hour postinjection, alcohol decreased total brain gangliosides (p less than 0.03) at 1 and 2 g/kg, but not at 3, 4, and 6 g/kg. Free whole-brain sialic acid was increased by 2 g/kg alcohol, which is consistent with the observed decrement in gangliosides at this dose. However, activity of sialidase on the endogenous substrates was not greatly affected by 2 g/kg of alcohol, indicating that ganglioside decrement is probably not attributable to activation of the catabolic enzyme. These results confirm and extend our earlier reports that incriminated gangliosides in the acute action of alcohol. The data also raise the possibility that the effect is due to the "excitatory," rather than the depressive actions of alcohol. Moreover, the action may involve an increased hydrolysis of membrane gangliosides by sialidase.