Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data are consistent with the proposed long-distance migration from Pannonia to Northern Italy.

Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards , a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early Medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs.Finally, our data was consistent with the proposed long-distance migration from Pannonia to Northern Italy.

BackgroundUse of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca2+-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects.MethodsTo address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies.ResultsAlthough both cell types express TRPV1 mRNA, neither responded to vanilloids with Ca2+-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1–50 nM) of vanilloids. The TRPV1-mediated and non-receptor specific Ca2+-cytotoxity ([RTX]>15 µM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediated Ca2+-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes.ConclusionTRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials.

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After 568 AD the Avars settled in the Carpathian Basin and founded the Avar Qaganate that was an important power in Central Europe until the 9th century. Part of the Avar society was probably of Asian origin; however, the localisation of their homeland is hampered by the scarcity of historical and archaeological data. Here, we study mitogenome and Y chromosomal variability of twenty-six individuals, a number of them representing a well-characterised elite group buried at the centre of the Carpathian Basin more than a century after the Avar conquest. The studied group has maternal and paternal genetic affinities to several ancient and modern East-Central Asian populations. The majority of the mitochondrial DNA variability represents Asian haplogroups (C, D, F, M, R, Y and Z). The Y-STR variability of the analysed elite males belongs only to five lineages, three N-Tat with mostly Asian parallels and two Q haplotypes. The homogeneity of the Y chromosomes reveals paternal kinship as a cohesive force in the organisation of the Avar elite strata on both social and territorial level. Our results indicate that the Avar elite arrived in the Carpathian Basin as a group of families, and remained mostly endogamous for several generations after the conquest. The Carpathian Basin in East-Central Europe is generally regarded as the westernmost point of the Eurasian steppe, and as such, its history was often influenced by the movements of nomadic people of eastern origin. After 568 AD, the Avars settled in the Carpathian Basin and founded their empire which was a powerful player in the geopolitical arena of Central and Eastern Europe for a quarter of a millennium 1,2. The hypothesis of the Asian origin of the Avars appeared as early as the 18th century. Since then various research approaches emerged indicating different regions as their home of origin: i.e. Central or East-Central Asia (see SI chapter 1b for explanation of this geographic term). This debate remained unresolved, however a rising number of evidences points towards the latter one 1,2. The history of the Avars is known from external, mainly Byzantine written accounts of diplomatic and historical character focusing on certain events and important people for the Byzantine Empire. As an example, the description of a Byzantine diplomatic mission in 569-570 AD visiting the Western Turkic Qaganate in Central Asia, claimed that their ruler complained about the escape of his subjects, the Avars 2-4. The linguistic data concerning the Avars are limited to a handful of personal names and titles (Qagan, Bayan, Yugurrus, Tarkhan, etc.) mostly of East-Central Asian origin, known from the same Byzantine written accounts.