Molekularbiologische Parameter liegemilieubedingter Knochenalterung - Implikationen für die biologische Spurenkunde

Die postmortale Alterung von Knochen (Diagenese) besteht aus einer sehr komplexen Serie von Prozessen, welche auf allen Ebenen seiner Organisation (makromorphologisch, mikro- und ultrastrukturell, molekular) erfolgt und entscheidend von Umweltfaktoren geprägt wird. In der vorliegenden Untersuchung wurde der Diagenesestatus von 127 archäologischem Knochen mit unterschiedlichen Liegezeiten (ca. 11500 bis 400 Jahren), auf mehreren Ebenen (Mikrostruktur, Biomoleküle, mineralische Matrix) festgestellt und diskutiert. Durch die Untersuchung von experimentell gealtertem Knochenmaterial konnten zusätzlich rein chemische Diageneseprozesse auf den untersuchten Ebenen nachvollzogen werden. Weiterhin wurde eine kleine Stichprobe von zehn modernen kremierten Knochen analysiert. Es ließen sich drei verschiedene Typen des diagenetischen Knochenstatus aufstellen (Diagenesetypen). Die histologische Knochenebene wurde als die Ebene erkannt, welche die meisten Informationen über den Erhaltungsstatus der anderen Merkmale liefern kann. Mit ihr hängt die Ausprägung der Fluoreszenz von Knochenquerschnitten bei Betrachtung unter UV-Licht zusammen. Folglich können diese beiden Merkmale als Indikatoren für den Diagenesetyp einer Knochenprobe dienen. Die Erfolgsaussichten der in der biologischen Spurenkunde angewandten Methoden hängen wesentlich von dem Ausmaß der postmortalen Knochenalterung ab. So ist es für die Analyse von größter Bedeutung, die Auswirkung der verschiedenen Einflussfaktoren auf die unterschiedlichen Ebenen der Knochenalterung zu erkennen und zu verstehen, um das biologische Signal von Dekompositionsartefakten trennen zu können. Durch die Erkenntnisse zu diagenetischen Abbauprozessen und Erhaltungszuständen des Knochens konnten in der vorliegenden Untersuchung die Möglichkeiten und Grenzen verschiedener spurenkundlicher Analysemethoden überprüft (DNA-Analysen, Analysen stabiler Isotope leichter Elemente) werden. Insbesondere wurden die Kriterien für die Validisierung stabiler Isotopendaten aus Kollagen betrachtet: Die Analysen zeigten, dass weder Kollagengehalt, noch C% und N% oder molare C/N-Verhältnis ausreichen, um diagenetisch veränderte Isotopenverhältnisse auszuschließen. Die Veränderung von Isotopenverhältnissen beruht mehrheitlich auf einer Veränderung der Aminosäurekomposition des Kollagens. Die Erstellung eines Aminosäureprofils ist daher unerlässlich für die Prüfung der Validität der Ergebnisse stabiler Isotopenanalysen. Die Prüfung der Zusammenhänge verschiedener Merkmale ermöglichte die Entwicklung und Überprüfung von Screeningmethoden für Kollagen- und DNA-Gehalt

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

Yersinia pestis DNA from Skeletal Remains from the 6(th) Century AD Reveals Insights into Justinianic Plague.

Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics

Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA

BACKGROUND Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, 'SOFIA'. PATIENTS AND METHODS INCLUSION CRITERIA WERE: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m(2). In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics. RESULTS Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3-4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin. CONCLUSION Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities

Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria

Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago

Research potential and limitations of trace analyses of cremated remains

Human cremation is a common funeral practice all over the world and willpresumably become an even more popular choice for interment in thefuture. Mainly for purposes of identification, there is presently agrowing need to perform trace analyses such as DNA or stable isotopeanalyses on human remains after cremation in order to clarify pendingquestions in civil or criminal court cases. The aim of this study was toexperimentally test the potential and limitations of DNA and stableisotope analyses when conducted on cremated remains.For this purpose, tibiae from modern cattle were experimentally crematedby incinerating the bones in increments of 100 degrees C until a maximumof 1000 degrees C was reached. In addition, cremated human remains werecollected from a modern crematory. The samples were investigated todetermine level of DNA preservation and stable isotope values (C and Nin collagen, C and O in the structural carbonate, and Sr in apatite).Furthermore, we assessed the integrity of microstructural organization,appearance under UV-light, collagen content, as well as the mineral andcrystalline organization. This was conducted in order to provide ageneral background with which to explain observed changes in the traceanalyses data sets. The goal is to develop an efficacious screeningmethod for determining at which degree of burning bone still retains itsoriginal biological signals. We found that stable isotope analysis ofthe tested light elements in bone is only possible up to a heat exposureof 300 degrees C while the isotopic signal from strontium remainsunaltered even in bones exposed to very high temperatures. DNA-analysesseem theoretically possible up to a heat exposure of 600 degrees C butcan not be advised in every case because of the increased risk ofcontamination. While the macroscopic colour and UV-fluorescence ofcremated bone give hints to temperature exposure of the bone’s outersurface, its histological appearance can be used as a reliable indicatorfor the assessment of the overall degree of burning

Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes

The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541–750 AD), suggesting a comparable evolutionary trajectory of Y. pestis during both events