Soziale Stratifizierung im frühen Mittelalter

Soziale Unterschiede innerhalb von Populationen sind ein zentraler Forschungsgegenstand der Archäologie und Anthropologie. Diese Arbeit beschäftigt sich mit der Frage, ob es biologische Indikatoren gibt, die mit sozialem Stand korrelieren und ob diese verwendet werden können, den sozialen Stand eines Individuums oder einer Gruppe festzustellen. Zu diesem Zweck wurden vier frühmittelalterliche „Separatfriedhöfe“ und ein Reihengräberfeld im Hinblick auf demographische Aspekte, degenerative Veränderungen der Gelenke, Ernährung und Migration untersucht. Die ausgewerteten Friedhöfe (Bruckmühl, Etting, Enkering und Großmehring) liegen im südlichen Bayern in der Grenzregion zum damaligen fränkischen Herrschaftsgebiet. Sie wurden archäologisch in die späte Merowingerzeit (ca. 650-720 n. Chr.) datiert. Zu dieser Zeit war das Herzogtum Bayern ein autonomer Teil des fränkischen Reiches. Um 700 n. Chr. fand ein politischer Umbruch statt und die aufstrebende Dynastie der Karolinger (beginnend mit Karl Martell) versuchte ihre Herrschaft auf bajuwarischem Gebiet zu festigen. In dieser Zeit fand ein deutlicher gesellschaftlicher Umbruch statt: Die alten Gesellschaftsstrukturen, die sich in der Sitte widerspiegeln, die Verstorbenen „alle gleich“ in Reihengräbern zu bestatten, lösen sich auf und einige Personen separieren sich nun in der Art ihrer Bestattungen demonstrativ vom Rest der Bevölkerung. Es erscheinen, parallel zu den üblichen Reihengräberfeldern, so genannte „Separatfriedhöfe“. Diese kleinen Friedhöfe mit etwa 30-40 Bestattungen zeichnen sich durch ihre spezifischen Grabstrukturen und ihre reiche Beigabenausstattung aus, und könnten demnach eine entstehende soziale Oberschicht repräsentieren. Eine Hypothese wäre, dass es sich bei den auf Separatfriedhöfen Bestatteten um fränkische „Adelige“ handelt, die von den Herrschern als lokale Exekutive, als eine Art „Verwaltungsangestellte“ eingesetzt wurden. Auch im Kontext mit der Ausbreitung des Christentums im Frühmittelalter werden die Anfänge eines feudalen Gesellschaftssystems erkennbar. Anhand der Friedhofsstruktur und der Beigabenausstattung wäre eine Zweiteilung der Separatgrablegen denkbar. Die Gräber wurden daher in Friedhofskategorien eingeteilt: Reich ausgestattete Zentralgräber und deren umgebende Gräber auf der einen Seite, einfache Bestattungen auf der anderen Seite des Separatfriedhofs und, im Fall des Bestattungsplatzes Großmehring, mit dem des Reihengräberfeldes eine weitere Kategorie. Um mögliche soziale Abstufungen festzustellen wurden zunächst das Sterbealter und das Geschlecht jedes Individuums (n=158) morphologisch bestimmt. Zusätzlich fand bei Erwachsenen die TCA-Methode (tooth cementum annulation) zur Sterbealtersbestimmung Verwendung. Zur vereinfachten quantitativen Auswertung der Zahnzementringe aus den histologischen Zahnquerschnitten wurde in einer Zusammenarbeit mit dem Fachbereich Informatik der FH Rosenheim ein automatisiertes Zählprogramm entwickelt. Die demographische Rekonstruktion aus den Sterbedaten zeigt, dass die Populationen der Separatgrablegen im Gegensatz zu der Population des Reihengräberfeldes eine niedrigere Kindersterblichkeit und eine höhere Lebenserwartung aufweisen. Darüber hinaus wurde jedes erwachsene Individuum morphologisch im Hinblick auf degenerative Veränderungen der Gelenke und der Wirbelsäule untersucht. Es zeigen sich keine Geschlechtsunterschiede und die allgemeine körperliche Belastung der Individuen auf allen ausgewerteten Friedhöfen scheint altersgemäß und relativ gering gewesen zu sein. Interessanterweise zeigte sich kein signifikanter Unterschied zwischen Separatfriedhof und Reihengräberfeld. Die Ergebnisse der Wirbelsäule zeigten einen unerwarteten Unterschied: Separat bestattete Männer waren in einem höheren Maß belastet als Männer auf dem Reihengräberfeld. Anhand von physischen Aktivitätsmustern und Belastung der Gelenke konnte hier keine soziale Abstufung festgestellt werden. Diese scheinen vielmehr von individuellen Aktivitäten, Arbeitsbelastungen, Krankheiten und Prädispositionen abhängig zu sein. Ein weiterer Indikator für gute Lebensbedingungen ist die Qualität der Nahrung. Daher wurde das 13C/12C und 14N/15N-Isotopenverhältnis des Knochenkollagens, mit Fokus auf den „Trophiestufeneffekt“ des 15N-Isotops untersucht. Der Verzehr von tierischem Eiweiß führt zu einer Anreicherung von 15N im Knochenkollagen. Unter der Annahme, dass zu dieser Zeit hauptsächlich wohlhabende und / oder höher gestellt Personen Zugang zu tierischen Proteinen (Fleisch, Eiern und Milchprodukten) hatten, können hohe δ15N-Werte einen höheren sozialen Status widerspiegeln und eine „hierarchische Abstufung“ zeigen. Im direkten Vergleich der δ15N-Werte der verschiedenen Friedhofsklassen sind keine signifikanten Unterschiede erkennbar, aber die Werte der Individuen aus den reich ausgestatteten Gräbern erscheinen leicht erhöht. Es besteht in Etting sogar ein signifikant abfallender Gradient zwischen den Zentralgräbern, über deren assoziierte Gräber zu dem Hauptteil der Gräber, im Fall von Großmehring eine abfallende Tendenz bis zum Reihengräberfeld. Bei Bruckmühl und dem Vergleichsfriedhof Kelheim sind keine Unterschiede nachweisbar. Zusammenfassend kann gesagt werden, dass biologische Indikatoren wie Kindersterblichkeit und Ernährung Hinweise auf den sozialen Rang eines Individuums geben können. Die Auswertung anhand der Voreinteilung in „Friedhofsklassen“ erwies sich jedoch als problematisch. Zusätzlich wurde die Sauerstoff- und Strontium-Isotopen Verhältnisse einiger ausgewählter Individuen untersucht, um zu testen, ob es sich bei Personen, die mit nicht-lokalen Beigaben oder in „exklusiven“ Gräbern bestattet wurden möglicherweise um „Ortsfremde“ handelt. Bei den meisten dieser Individuen zeigte die Isotopenzusammensetzung jedoch „lokale“ Signaturen, lediglich ein Mann muss seine Kindheit in einem anderen geologischen Gebiet verbracht haben. Die Theorie, dass es sich bei den auf Separatfriedhöfen bestatteten Gruppen um „fränkische Verwaltungsangestellte“ handelt konnte nicht bestätigt werden. Diese archäo-biologische Untersuchung der Separatfriedhöfe leistet einen Beitrag zum Verständnis des Entstehungsprozesses gesellschaftlicher Strukturen im frühen Mittelalter. Sie kann als Ausgangspunkt für weitere Studien dienen, um mit Hilfe archäologischer und anthropologischer Methoden Entwicklungen in historischen Gesellschaften beleuchten, deren geschichtliche Hintergründe mangels schriftlicher Quellen weitgehend im Dunkeln liegen

Tracing early life histories from Roman times to the Medieval era: weaning practices and physiological stress

and cultural factors. While infant feeding strategies vary across different regions and historical eras, the associated transition from breastmilk to solid foods is universally thought to be stressful. However, still little is known about infant feeding practices and possibly associated stress in former times. This also applies to the period of transition from classical antiquity to medieval times, which shaped modern Western civilization. To enhance the understanding of childhood nutrition and stress during this period, we first analyzed stable carbon and nitrogen isotopes in serial dentine samples from the first molars of 38 individuals buried in the region once known as the Roman frontier province of Raetia secunda, now encompassing Southern Bavaria. In addition, we investigated the presence of linear enamel hypoplasia (LEH), known to be a marker of unspecific physiological stress, within their dentition. We used this data to create isotope profiles that display dietary changes in comparison with the occurrence of LEH. We found highly variable δ15N and δ13C values and different shapes of isotope profiles which indicate different nutrition of breastfeeding individuals, complementary foods and post-weaning diets, and individual weaning patterns. For most individuals, the weaning process was completed between the ages of two and three. Interestingly, some females of non-local origin show longer weaning periods, likely displaying the influence of different cultural practices in other communities. We also found that LEH most frequently occurred in the post-weaning phase, which supports the assumption that children were at increased risk once breastfeeding had ceased completely. Furthermore, a change in the post-weaning diet in the seventh century coincided with an increased prevalence of LEH, indicating that the foods chosen or available during this time affected the susceptibility of children to stress. In conclusion, our study unveiled diverse infant feeding strategies practiced across various communities, both in different historical eras and geographical locations

The “post-weanling’s conundrum”: exploring the impact of infant and child feeding practices on early mortality in the Bronze Age burial cave of Moro de Alins, north-eastern Iberia, through stable isotope analysis

Producción CientíficaThe relationship between infant and child feeding practices and early mortality is difficult to address in past societies. Here, stable carbon (δ13C) and nitrogen (δ15N) isotope measurements of bulk bone and sequential dentine samples of deciduous second and/or permanent first molars of four younger children, one older child, one late adolescent, and two young adults (n = 8) from Moro de Alins cave, north-eastern Iberia, are used to explore the potential impact of early-life nutrition on mortality in the Bronze Age. Isotope results are compatible with generally short exclusive breastfeeding and standard weaning periods compared to other pre-modern populations. However, there are differences in exclusive breastfeeding mean δ13C values and in Δ13C trophic shifts between exclusive breastfeeding and immediate post-weaning isotope values for those individuals who survived into adolescence and adulthood and those who did not. While the former seem to be consistent with trophic distances published for modern mother–infant pairs, the latter are above most of them. This may suggest that individuals who consumed similar foods to their mothers or suffered from less physiological stress during or after weaning had greater chances of survival during early childhood and beyond. Post-weaning seems to have been a particularly stressful period of life, where a number of instances of patterns of opposing isotopic covariance compatible with catabolic changes, often preceding death among non-survivors, are detected. This outcome shows the key role of nutritional and/or physiological status in early-life morbidity and mortality among partially and especially fully weaned children from pre-antibiotic, pre-vaccination, and poor sanitation contexts and proposes that adult survival is rooted in early life experiences, in keeping with the developmental origins of health and disease.This work was supported and funded by the British Academy under the Newton International Fellowship NF170854European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 790491Ministerio de Ciencia e Innovación under the project (HAR2015-65620-P)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2

INTRODUCTION: Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo. METHODS: Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry. RESULTS: In wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects. CONCLUSIONS: TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists

Assessing the reliability of microbial bioerosion features in burnt bones: a novel approach using feature-labelling in histotaphonomical analysis

Objectives Recent histotaphonomic studies have focused on the presence of features thought to be caused either by bacteria (microscopic focal destruction/MFD and cyanobacterial tunnelling) or fungal (Wedl tunnelling types 1 and 2) attack on unburnt bone. Identifying these characteristics on burnt bones could indicate the state of decomposition before burning, with important repercussions for both archaeological and forensic contexts. Materials and Methods Fleshed pig (Sus scrofa, N = 25) tibiae were left exposed on a field, then collected at 14-, 34-, 91-, 180-, 365-day intervals before being burnt in an outdoor fire (≤750 °C). Fresh (fleshed) legs (N = 10) acted as unburnt and burnt controls. Thin sections were examined using transmitted light microscopy and backscattered scanning electron microscopy. Diagenetic traits were quantitatively and systematically assessed by a novel data labelling application developed for this study. Results Features meeting the published characteristics of microbial bioerosion (‘Wedl tunnelling’, ‘lamellate’ and ‘budded MFD’) were significantly correlated with time since deposition on the unburnt bones. Only budded MFD increased significantly over time in the burnt groups. However, the presence features meeting the published characteristics of Wedl 2 tunnelling were present on the fresh burnt bones, indicating that they are an artefact. Discussion The presence of many features seemingly indistinguishable from those caused by bioerosion on the freshly burnt control bones suggests that burning is not only able to conceal features thought to be the result of bioerosion but can produce them as well. Thus, such features are not a reliable indication of bioerosion. Budded MFD may be a viable indicator but more research is required

Hepatitis C Virus Induced Endothelial Inflammatory Response Depends on the Functional Expression of TNF alpha Receptor Subtype 2

In hepatitis C virus (HCV) infection, morbidity and mortality often result from extrahepatic disease manifestations. We provide evidence for a role of receptors of the innate immune system in virally induced inflammation of the endothelium in vitro and in vivo. Corresponding to the in vitro finding of an HCV-dependent induction of proinflammatory mediators in endothelial cells, mice treated with poly (I: C) exhibit a significant reduction in leukocyte rolling velocity, an increase in leukocyte adhesion to the vessel wall and an increased extravasation of leukocytes. HCV directly promotes activation, adhesion and infiltration of inflammatory cells into the vessel wall by activation of endothelial viral receptors. Poly (I: C) induces the expression of TLR3 in vivo and hereby allows for amplification of all of the aforementioned responses upon viral infection. Proinflammatory effects of viral RNA are specifically mediated by TLR3 and significantly enhanced by tumor necrosis factor alpha (TNFa). HCV-RNA induces the endothelial expression of TNFa and TNFa receptor subtype 2 and we provide evidence that leucocyte adhesion and transmigration in response to activation of viral RNA receptors seem to depend on expression of functional TNFR2. Our results demonstrate that endothelial cells actively participate in immune mediated vascular inflammation caused by viral infections

Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium

Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells. Transfection of cultured human endothelial cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood clotting in vitro, which was partly dependent on RIG-I signalling. Prothrombotic effects were also observed upon transfection of endothelial cells with hepatitis B virus DNA-containing immunoprecipitates as well human genomic DNA. In addition, dsDNA led to surface expression of von Willebrand factor resulting in increased platelet-endothelium-interactions under flow. Eventually, intrascrotal injection of dsDNA resulted in accelerated thrombus formation upon light/dye-induced endothelial injury in mouse cremaster arterioles and venules in vivo. In conclusion, we show that viral or endogenous dsDNA induces a prothrombotic phenotype in the vascular endothelium. These findings represent a novel link between pathogen-and danger-associated patterns within innate immunity and thrombosis

Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in sepsis

Background: Sepsis, the most severe form of infection, involves endothelial dysfunction which contributes to organ failure. To improve therapeutic prospects, elucidation of molecular mechanisms underlying endothelial vascular failure is of essence. Methods: Polymicrobial contamination induced sepsis mouse model and primary endothelial cells incubated with sepsis serum were used to study SHP-2 in sepsis-induced endothelial inflammation. SHP-2 activity was assessed by dephosphorylation of pNPP, ROS production was measured by DCF oxidation and protein interactions were assessed by proximity ligation assay. Vascular inflammation was studied in the mouse cremaster model and in an in vitro flow assay. Findings: We identified ROS-dependent inactivation of the tyrosine phosphatase SHP-2 to be decisive for endothelial activation in sepsis. Using in vivo and in vitro sepsis models, we observed a significant reduction of endothelial SHP-2 activity, accompanied by enhanced adhesion molecule expression. The impaired SHP-2 activity was restored by ROS inhibitors and an IL-1 receptor antagonist. SHP-2 activity inversely correlated with the adhesive phenotype of endothelial cells exposed to IL-1β as well as sepsis serum via p38 MAPK and NF-κB. In vivo, SHP-2 inhibition accelerated IL-1β-induced leukocyte adhesion, extravasation and vascular permeability. Mechanistically, SHP-2 directly interacts with the IL-1R1 adaptor protein MyD88 via its tyrosine 257, resulting in reduced binding of p85/PI3-K to MyD88. Interpretation: Our data show that SHP-2 inactivation by ROS in sepsis releases a protective break, resulting in endothelial activation. Fund: German Research Foundation, LMU Mentoring excellence and FöFoLe Programme, Verein zur Förderung von Wissenschaft und Forschung, German Ministry of Education and Research. Keywords: Endothelial cells, IL-1β, MyD88, ROS, SHP-2, Sepsi

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10), chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function

A guide for an anatomically sensitive dentine microsampling and age-alignment approach for human teeth isotopic sequences

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