Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

In the developing chicken embryo yolk sac vasculature, the expression of arterial identity genes requires arterial hemodynamic conditions. We hypothesize that arterial flow must provide a unique signal that is relevant for supporting arterial identity gene expression and is absent in veins. We analyzed factors related to flow, pressure and oxygenation in the chicken embryo vitelline vasculature in vivo. The best discrimination between arteries and veins was obtained by calculating the maximal pulsatile increase in shear rate relative to the time-averaged shear rate in the same vessel: the relative pulse slope index (RPSI). RPSI was significantly higher in arteries than veins. Arterial endothelial cells exposed to pulsatile shear in vitro augmented arterial marker expression as compared with exposure to constant shear. The expression of Gja5 correlated with arterial flow patterns: the redistribution of arterial flow provoked by vitelline artery ligation resulted in flow-driven collateral arterial network formation and was associated with increased expression of Gja5. In situ hybridization in normal and ligation embryos confirmed that Gja5 expression is confined to arteries and regulated by flow. In mice, Gja5 (connexin 40) was also expressed in arteries. In the adult, increased flow drives arteriogenesis and the formation of collateral arterial networks in peripheral occlusive diseases. Genetic ablation of Gja5 function in mice resulted in reduced arteriogenesis in two occlusion models. We conclude that pulsatile shear patterns may be central for supporting arterial identity, and that arterial Gja5 expression plays a functional role in flow-driven arteriogenesis.

Identity, Philosophy, and the Problem of Armenian History in the Sixth Century

History and Identity in the Late Antique Near East gathers together the work of distinguished historians and early career scholars with a broad range of expertise to investigate the significance of newly emerged, or recently resurrected, ethnic identities on the borders of the eastern Mediterranean world. It focuses on the "long late antiquity" from the eve of the Arab conquest of the Roman East to the formation of the Abbasid caliphate. The first half of the book offers papers on the Christian Orient on the cusp of the Islamic invasions. These papers discuss how Christians negotiated the end of Roman power, whether in the selective use of the patristic past to create confessional divisions or the emphasis of the shared philosophical legacy of the Greco-Roman world. The second half of the book considers Muslim attempts to negotiate the pasts of the conquered lands of the Near East, where the Christian histories of Hira or Egypt were used to create distinctive regional identities for Arab settlers. Like the first half, this section investigates the redeployment of a shared history, this time the historical imagination of the Qu'ran and the era of the first caliphs. All the papers in the volume bring together studies of the invention of the past across traditional divides between disciplines, placing the re-assessment of the past as a central feature of the long late antiquity. As a whole, History and Identity in the Late Antique Near East represents a distinctive contribution to recent writing on late antiquity, due to its cultural breadth, its interdisciplinary focus, and its novel definition of late antiquity itself.