Edelen in Zeeland : macht, rijkdom en status in een laatmiddeleeuwse samenleving

It has long been assumed that the position of nobility in the Low Countries weakened in the later Middle Ages. Though the narrative of a crisis of the late medieval nobility is no longer taken for granted, it still exerts influence on historiography. This book sketches the contours of the noble population in the county of Zeeland between 1400 and 1550, thereby answering the central question of how the political and socio-economic position of the noblemen in society actually evolved in a period characterised by the processes of state formation, urbanisation and commercialisation. The question is approached from two perspectives: that of the nobility as a group and that of the individual nobleman and his family. On the one hand, it is traced how changes in the political and socio-economic circumstances affected the power, wealth and status of the nobility. On the other, the strategies of the nobles to consolidate their estate by adapting to the changing political and economic field are analysed. The specific political history and social institutions of Zeeland were of great influence on the structure of the noble population, the social reproduction strategies of the nobles, and the appreciation of nobility. The late medieval nobility in Zeeland should not be understood as a strong co-operative group, but rather as a group of individuals with the same legal status but different political and socio-economic profiles. They belonged to several overlapping social networks. As such the nobility retained its stability and continuity, although the identity and lifestyle that nobles shared became less connected to chivalry and more related to loyal state service in the sixteenth century.LEI Universiteit LeidenCollective identities and transnational networks in medieval and early modern Europe, 1000-180

A rare missense mutation in <i>GJB3</i> (Cx31G45E) is associated with a unique cellular phenotype resulting in necrotic cell death

Erythrokeratodermia variabilis et progressiva (EKV-P) is caused by mutations in either the GJB3 (Cx31) or GJB4 genes (Cx30.3). We identified a rare GJB3 missense mutation, c.134G>A (p.G45E), in two unrelated patients and investigated its cellular characteristics. Expression of Cx31G45E-GFP caused previously undescribed changes within HeLa cells and HaCaT cells, a model human keratinocyte cell line. Cx31WT-GFP localised to the plasma membrane, but expression of Cx31G45E-GFP caused vacuolar expansion of the endoplasmic reticulum (ER), the mutant protein accumulated within the ER membrane and disassembly of the microtubular network occurred. No ER stress responses were evoked. Cx31WT-myc-myc-6xHis and Cx31G45E-GFP co-immunoprecipitated, indicative of heteromeric interaction, but co-expression with Cx31WT-mCherry, Cx26 or Cx30.3 did not mitigate the phenotype. Cx31 and Cx31G45E both co-immunoprecipitated with Cx43, indicating the ability to form heteromeric connexons. WT-Cx31 and Cx43 assembled into large gap junction plaques at points of cell-to-cell contact; Cx31G45E restricted the ability of Cx43 to reach the plasma membrane in both HaCaT cells and HeLa cells stably expressing Cx43 where the proteins strongly co-localised with the vacolourised ER. Cell viability assays identified an increase in cell death in cells expressing Cx31G45E-GFP, which FACS analysis determined was necrotic. Blocking connexin channel function with 18α-glycyrrhetinic acid did not completely rescue necrosis or prevent propidium iodide uptake, suggesting that expression of Cx31G45E-GFP damages the cellular membrane independent of its channel function. Our data suggest that entrapment of Cx43 and necrotic cell death in the epidermis could underlie the EKV skin phenotype

Local rewiring of genome-nuclear lamina interactions by transcription

Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation of such genes is often accompanied by repositioning toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are poorly understood. We addressed these questions by systematic activation or inactivation of individual genes, followed by detailed genome-wide analysis of NL interactions, replication timing, and transcription patterns. Gene activation inside LADs typically causes NL detachment of the entire transcription unit, but rarely more than 50-100 kb of flanking DNA, even when multiple neighboring genes are activated. The degree of detachment depends on the expression level and the length of the activated gene. Loss of NL interactions coincides with a switch from late to early replication timing, but the latter can involve longer stretches of DNA. Inactivation of active genes can lead to increased NL contacts. These extensive datasets are a resource for the analysis of LAD rewiring by transcription and reveal a remarkable flexibility of interphase chromosomes