NAADP regulates human platelet function.

Platelets play a vital role in maintaining haemostasis. Human platelet activation depends on Ca2+ release, leading to cell activation, granule secretion and aggregation. NAADP (nicotinic acid-adenine dinucleotide phosphate) is a Ca2+-releasing second messenger that acts on acidic Ca2+ stores and is used by a number of mammalian systems. In human platelets, NAADP has been shown to release Ca2+ in permeabilized human platelets and contribute to thrombin-mediated platelet activation. In the present study, we have further characterized NAADP-mediated Ca2+ release in human platelets in response to both thrombin and the GPVI (glycoprotein VI)-specific agonist CRP (collagen-related peptide). Using a radioligand-binding assay, we reveal an NAADP-binding site in human platelets, indicative of a platelet NAADP receptor. We also found that NAADP releases loaded 45Ca2+ from intracellular stores and that total platelet Ca2+ release is inhibited by the proton ionophore nigericin. Ned-19, a novel cell-permeant NAADP receptor antagonist, competes for the NAADP-binding site in platelets and can inhibit both thrombin- and CRP-induced Ca2+ release in human platelets. Ned-19 has an inhibitory effect on platelet aggregation, secretion and spreading. In addition, Ned-19 extends the clotting time in whole-blood samples. We conclude that NAADP plays an important role in human platelet function. Furthermore, the development of Ned-19 as an NAADP receptor antagonist provides a potential avenue for platelet-targeted therapy and the regulation of thrombosis.

Globalisation and the evolution of international retailing: a comment on Alexander's 'British overseas retailing, 1900-1960'

Nicholas Alexander's (2011. British overseas retailing, 1900–60: International firm characteristics, market selections and entry modes. Business History, 53, 530–556) survey of British overseas retailers from 1900 to 1960 provides pathbreaking new evidence of international retailing activity during the first globalisation boom. The article surveys this and other recent evidence, and confirms that international retailing was far more significant up to 1929 than previously thought. This activity was overwhelmingly undertaken by non-retailers, however, and hence by multinationals whose advantages in retailing were fundamentally unsustainable over the long run. Even the department store format, the principal retail innovation of the period, was not internationalised primarily by multinationals. Rather it was diffused via indigenous entrepreneurs, driven by a rapidly growing global demand for western style fashion and dress.

The Gift of the Nile: Hellenizing Egypt from Aeschylus to Alexander

The Egyptians mesmerized the ancient Greeks for scores of years. The Greek literature and art of the classical period are especially thick with representations of Egypt and Egyptians. Yet despite numerous firsthand contacts with Egypt, Greek writers constructed their own Egypt, one that differed in significant ways from actual Egyptian history, society, and culture. Informed by recent work on orientalism and colonialism, this book unravels the significance of these misrepresentations of Egypt in the Greek cultural imagination in the fifth and fourth centuries B.C.E. Looking in particular at issues of identity, otherness, and cultural anxiety, Phiroze Vasunia shows how Greek authors constructed an image of Egypt that reflected their own attitudes and prejudices about Greece itself. He focuses his discussion on Aeschylus Suppliants; Book 2 of Herodotus; Euripides' Helen; Plato's Phaedrus, Timaeus, and Critias; and Isocrates' Busiris. Reconstructing the history of the bias that informed these writings, Vasunia shows that Egypt in these works was shaped in relation to Greek institutions, values, and ideas on such subjects as gender and sexuality, death, writing, and political and ethnic identity. This study traces the tendentiousness of Greek representations by introducing comparative Egyptian material, thus interrogating the Greek texts and authors from a cross-cultural perspective. A final chapter also considers the invasion of Egypt by Alexander the Great and shows how he exploited and revised the discursive tradition in his conquest of the country. Firmly and knowledgeably rooted in classical studies and the ancient sources, this study takes a broad look at the issue of cross-cultural exchange in antiquity by framing it within the perspective of contemporary cultural studies. In addition, this provocative and original work shows how Greek writers made possible literary Europe's most persistent and adaptable obsession: the barbarian.