TENDENCIA THATCHERITIS OR ENGLISHNESS REMADE: The Fictions of Julian Barnes, Hanif Kureishi and Pat Barker

Julian Barnes, Pat Barker, and Hanif Kureishi are all canonical authors whose fictions are widely believed to reflect the cultural and political state of a nation that is post-war, post-imperial and post-modern. While much has been written on how Barker’s and Kureishi’s early works in particular respond to and intervene in the presiding political narrative of the 1980s – Thatcherism – treatment of how revenants of Thatcherism have shaped these writers’ works from 1990 on has remained cursory. Thatcherism is more than an obvious historical reference point for Barker, Barnes, and Kureishi; their works demonstrate a sophisticated understanding of how Thatcher’s reworkings of the repertoires of Englishness – a representational as well as political and cultural endeavour – persist beyond her time in office. Barnes, Barker, and Kureishi seem to have reached the same conclusion as political and cultural critics: Thatcher and Thatcherism have remade not only the contemporary political and cultural landscapes but also the electorate and consequently the English themselves. Tony Blair’s conception of the New Britain proved less than satisfactory because contemporary repertoires of Englishness repeat and rework historical and not incidentally imperial formulations of England and Englishness rather than envision civic and populist formulations of renewal. Barnes’s England, England and Arthur & George confront the discourse of inevitability that has come to be attached to contemporary formulations of both political and cultural Englishness – both in terms of its predictable demise and its belated celebration. Kureishi’s The Buddha of Suburbia and “The Body” speak to an alteration that has taken place in which historical Englishness and Thatcherism have become complementary rather than contrasting discourses. What Barker’s Border Crossing and Double Vision offer against this backdrop is a subtle interrogation of how renewal itself comes to be a presiding mode of cultural reflection that absorbs revolutionary possibility.

Investigating the Role of cAMP-Signaling in the Regulation of Vascular Endothelial Cell Adaptive Responses to Fluid Shear Stress

The circulating blood exerts a force on the vascular endothelium, termed fluid shear stress (FSS), which directly impacts numerous vascular endothelial cell (VEC) functions. For example, high rates of linear and undisturbed (i.e. laminar) blood flow maintains a protective and quiescent VEC phenotype. Meanwhile, deviations in blood flow, which can occur at vascular branchpoints and large curvatures, create areas of low, and/or oscillatory FSS, and promote a pro-inflammatory, pro-thrombotic and hyperpermeable phenotype. Indeed, it is known that these areas are prone to the development of atherosclerotic lesions. Herein, we show that cyclic nucleotide phosphodiesterase (PDE) 4D (PDE4D) activity is increased by FSS in human arterial endothelial cells (HAECs) and that this activation regulates the activity of cAMP-effector protein, Exchange Protein-activated by cAMP-1 (EPAC1), in these cells. Importantly, we also show that these events directly and critically impact HAEC responses to FSS, especially when FSS levels are low. Both morphological events induced by FSS, as measured by changes in cell alignment and elongation in the direction of FSS, and the expression of critical FSS-regulated genes, including Krüppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS) and thrombomodlin (TM), are mediated by EPAC1/PDE4D signaling. At a mechanistic level, we show that EPAC1/PDE4D acts through the vascular endothelial-cadherin (VECAD)/ platelet-cell adhesion molecule-1 (PECAM1)/vascular endothelial growth factor receptor 2 (VEGFR2) mechanosensor to activate downstream signaling though Akt. Given the critical role of PDE4D in mediating these effects, we also investigated the impact of various patterns of FSS on the expression of individual PDE genes in HAECs. Notably, PDE2A was significantly upregulated in response to high, laminar FSS, while PDE3A was upregulated under low, oscillatory FSS conditions only. These data may provide novel therapeutic targets to limit FSS-dependent endothelial cell dysfunction (ECD) and atherosclerotic development.