Söldnerlandschaften. Frühneuzeitliche Gewaltmärkte im Vergleich

In einer Zeit, da private Sicherheits- und Militärunternehmungen an Bedeutung gewinnen und Staaten ihr Monopol auf die militärische Gewaltanwendung in zahlreichen asymmetrischen Kriegen aufzugeben scheinen, hat die Solddienstproblematik eine neue Aktualität gewonnen. Das bereits in der Antike betriebene Geschäft mit Söldnern erlebte in der Frühen Neuzeit seine Blüte. Die gesellschaftlichen, ökonomischen, kulturellen und politischen Implikationen dieses Gewaltmarkts sind deshalb ein wichtiges Thema für die Geschichte der Frühen Neuzeit. Der wissenschaftliche Diskurs wird allerdings stark von nationalen Narrativen dominiert. Diese unangemessene Engführung versucht der vorliegende Sammelband zu durchbrechen. In einer vergleichenden, transnationalen Perspektive wird die Frage, warum sich in der frühen Neuzeit bestimmte Räume zu erfolgreichen Absatzmärkten für Söldner entwickelt haben und somit zu Söldnerlandschaften geworden sind, von ausgewiesenen Fachleuten erörtert und diskutiert.

Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels

The level of body iron storage and the erythropoietic need for iron are indicated by the serum levels of ferritin and soluble transferrin receptor (sTfR), respectively. A meta-analysis of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters. The PCSK7 association was the most significant (rs236918, P = 1.1 × 10E-27) suggesting that proprotein convertase 7, the gene product of PCSK7, may be involved in sTfR generation and/or iron homeostasis. Conditioning the sTfR analyses on transferrin saturation abolished the HFE signal and substantially diminished the TMPRSS6 signal while the PCSK7 association was unaffected, suggesting that the former may be mediated by transferrin saturation whereas the PCSK7-associated effect on sTfR generation appears to be more direct.

Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis

Background Keratins 8 and 18 (K8/K18) are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. Methods The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene) mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. Results We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2%) and non-coding heterozygous variants in 6 additional patients (3.7%). Two novel K8 variants (Q169E/R275W) were found. K8 R341H was the most common amino-acid altering variant (4 patients), and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. Conclusion In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n = 954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P = 5 × 10(-4). Two population cohorts (KORA F3 and F4 with together n = 3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P = 0.00085) but not in the second replication step (joint nominal P-value = 0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.

Clinical versus pre-clinical FE models for vertebral body strength predictions

The finite element analysis is an accepted method to predict vertebral body compressive strength. This study compares measurements obtained from in vitro tests with the ones from two different simulation models: clinical quantitative computer tomography (QCT) based homogenized finite element (hFE) models and pre-clinical high-resolution peripheral QCT-based (HR-pQCT) hFE models. About 37 vertebral body sections were prepared by removing end-plates and posterior elements, scanned with QCT (390/450μm voxel size) as well as HR-pQCT (82μm voxel size), and tested in compression up to failure. Non-linear viscous damage hFE models were created from QCT/HT-pQCT images and compared to experimental results based on stiffness and ultimate load. As expected, the predictability of QCT/HR-pQCT-based hFE models for both apparent stiffness (r2=0.685/0.801r2=0.685/0.801) and strength (r2=0.774/0.924r2=0.774/0.924) increased if a better image resolution was used. An analysis of the damage distribution showed similar damage locations for all cases. In conclusion, HR-pQCT-based hFE models increased the predictability considerably and do not need any tuning of input parameters. In contrast, QCT-based hFE models usually need some tuning but are clinically the only possible choice at the moment.

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.

Ressourcenmanagement in historischer Perspektive

Der Begriff der Nachhaltigkeit taucht erstmals 1713 in der forstwirtschaftlichen Schrift „Sylvicultura oeconomica“ des sächsischen Kammer- und Bergrats Hans Carl von Carlowitz auf. Damit wird schon deutlich, dass sich Fragen eines nachhaltigen Umgangs mit Ressourcen im „Zeitalter des Holzes“ (Joachim Radkau) vornehmlich auf die Bewirtschaftung von Wäldern konzentrierten. Wälder boten einen der wichtigsten Baustoffe für Häuser, Mühlen und Brücken, Holz war lange Zeit der wichtigste Brennstoff. Schon für die Wälder im Besitz der mittelalterlichen Städte sind daher ausführliche Regelungen erhalten, die nachhaltiges Bewirtschaften erkennen lassen und zum Teil schwere Strafen gegen ein Zuwiderhandeln vorsehen. Das frühneuzeitliche Berg- und Hüttenwesen verbrauchte Unmengen an Holz für den Stollenbau und die Verhüttung, sodass Montanindustrie und Forstwirtschaft eigentlich gar nicht voneinander zu trennen sind. In der ersten Hälfte des 19. Jahrhunderts stand die nachhaltige Aufforstung von (Gebirgs-)Wäldern Pate bei der Einrichtung forstwirtschaftlich-akademischer Ausbildung, so auch in der Schweiz. Hauptziel der Aufforstung war jetzt der Schutz vor Überschwemmungen im Flachland, die man auf die zu umfangreiche, unkontrollierte Abholzung im Gebirge zurückführte. Bis ins 19. Jahrhundert konzentrierte sich daher der Nachhaltigkeitsdiskurs auf die Forstwirtschaft. Seitdem rücken auch der Abbau von Bodenschätzen, die Förderung fossiler Brennstoffe wie Erdöl und Erdgas sowie der nachhaltige Umgang mit Wasser in den Mittelpunkt. Aus Zeitgründen kann dabei aber nur mehr exemplarisch auf die Entstehung der Erdölindustrie seit dem Beginn des 20. Jahrhunderts eingegangen werden. Zusammenfassend kann somit festgestellt werden, dass ein nachhaltiges Bewirtschaften von Ressourcen, v.a. der Wälder, eine der wichtigsten Voraussetzungen für die Wirtschaft zwischen dem 14. und 19. Jahrhundert war, bzw. umgekehrt Bergbauregionen auch deswegen nicht mehr rentabel blieben, weil die Herbeischaffung von Holz über grosse Distanzen zu kostspielig wurde.