THE SYNTHESIS, KINETIC CHARACTERIZATION AND APPLICATION OF A NOVEL BIOTINYLATED AFFINITY LABEL FOR CATHEPSIN-B

In this study we report on the synthesis, kinetic characterization and application of a novel biotinylated and active-site-directed inactivator of cathepsin B. Thus the peptidyliazomethane biotinyl-Phe-Ala-diazomethane has been synthesized by a combination of solid-phase and solution methodologies and has been shown to be a very efficient inactivator of bovine and human cathepsin B. The respective apparent second-order rate constants (k0bs./[I]) for the inactivation of the human and bovine enzymes by this reagent, namely approximately 5.4 x 10(4) M-1 and approximately 7.8 x 10(4) M-1, compare very favourably with those values determined for the urethane-protected analogue benzloxycarbonyl-Phe-Ala-chloromethane first described by Green & Shaw [(1981) J.Biol. Chem. 256, 1923-1928], thus demonstrating that the presence of the biotin moiety at the P3 position is compatible with inhibitor effectiveness. The utilization of this reagent for the detection of cathepsin B in electrophoretic gels, using Western blotting and in combination with a streptavidin/alkaline phosphatase detection system, is also demonstrated. Given that the peptidydiazomethanes exhibit a pronounced reactivity towards cysteine proteinases, we feel that the present label may well constitute the archetypal example of a wide range of reagents for the selective labelling of this class of proteinase, even in a complex biological milieu containing additional classes of proteinases.

Review: R. Bellamy, D. Castiglione and J. Shaw (eds.), Making European Citizens (Palgrave Macmillan, 2006)

Review of edited collection.

The Bonds of Brotherhood: New Evidence of Sino-North Korean Exchanges, 1950-1954

Drawing on recently declassified documents from the archive of the Foreign Ministry of the People’s Republic of China (PRC), this article looks at China’s relationship with North Korea during and immediately after the Korean War. Although previous scholarship has touched on PRC–North Korean military ties during the war, this article is the first in-depth analysis of issues that are less well understood, notably China’s efforts to cope with a huge influx of refugees from North Korea, the PRC’s economic assistance during the war and in the early postwar reconstruction, and Chinese educational and ideological support for North Korean professionals and party cadres. The article shows that the extensive military coordination between Beijing and Pyongyang was only one way in which the war brought North Korea and the PRC into a closer relationship

Review of Bernard Lahire's 'The Plural Actor'

Book review of 'The Plural Actor' by Bernard Lahire

Knowledge, innovation and emulation in the evolutionary thought of Bernard Mandeville

Of the early modern writers on the division of labour, Bernard Mandeville alone extended it to all aspects of human activity and emphasised its role in a cumulative process of evolution in which each generation modified and built on what had been achieved by earlier generations. This required exploration of the mechanisms through which new knowledge was developed as well as the means by which knowledge was transmitted between the generations. The present article examines Mandeville’s treatment of these mechanisms and explores their theoretical origins. It examines Mandeville’s understanding of the role of the division of labour in facilitating discovery and learning and the role of education and imitation in transmitting social knowledge. It shows that, for Mandeville, innovators were people of ordinary capacity who were alert to the opportunities and challenges of their environment. As a result of specialisation, they possessed tacit knowledge which was actualised in what they did rather than in theoretical propositions. Mandeville’s evolutionary thought influenced subsequent writers on political economy and evolutionary social thinkers. It may also have had some influence on Charles Darwin, though it is not, in itself, Darwinian. © The Author 2013. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved.

Bernard Mandeville and the doctrine of laissez-faire

The view of Mandeville as a pioneer of laissez-faire is difficultto reconcile with his repeated insistence that private vices were turnedinto public benefits by the ‘dexterous management of the skilfulpolitician’. Even if references to the skilful politician are regarded asshorthand for a legal and institutional framework, there remains thequestion of whether such a framework is a spontaneous order or theproduct of purposeful experiment as Mandeville thought? Mandevillewarned about the harmful effects of meddling but his complaint wasabout the actions of fashionable do-gooders rather than government. Heunderstood that the voluntariness of a transaction could be regarded asa defence against complaints of unfairness but he was quick to pointout the limitations of voluntariness especially in the market for labour.Mandeville’s objective was to teach people what they are not what theyshould be. He pointed to the strengths of the emerging market systembut was not afraid to expose its faults.