Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants1–8 who received a limited amount of admixture from resident hunter-gatherers3–5,9. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Using the highest-resolution genome-wide ancient DNA data set assembled to date—a total of 180 samples, 130 newly reported here, from the Neolithic and Chalcolithic of Hungary (6000–2900 BCE, n = 100), Germany (5500–3000 BCE, n = 42), and Spain (5500–2200 BCE, n = 38)—we investigate the population dynamics of Neolithization across Europe. We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways that gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modeling approaches to elucidate multiple dimensions of historical population interactions.

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Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.

a b s t r a c tMacedonian Vranec wines were analysed by HPLC coupled with DAD and MS detections and by spectrophotometric methods. ESI-IT MS and MS-MS methods with alternating ionisation polarity were used for identification of the phenolic compounds. Both, nonflavonoids (stilbens, hydroxybenzoic and hydroxycinnamic acids and derivatives) and flavonoids (flavonols, flavan-3-ols and anthocyanins) were detected in the samples. Vranec wines were produced under different fermentation conditions: maceration time of 3, 6 and 10 days, two doses of SO 2 (30 and 70 mg l À1) and two yeasts for fermentation, in order to examine their effects on the extraction of phenolic compounds from grapes into the wine.