Bargaining, Nuclear Proliferation, and Interstate Disputes

Contrasting claims about the consequences of nuclear weapons rely on different interpretations about how leaders respond to risk, uncertainty, and the balance of power. Nuclear optimists use deterrence theory to argue that proliferation can promote stability and inhibit the use of force. Pessimists argue that proliferation precipitates nuclear hubris, accident, or anger that heightens the risk of war. It is also possible that nuclear weapons have no net effect on dispute propensity. Since states fashion their own bargains, nuclear status is bound to influence the distribution of influence. Proliferation also reflects existing tensions, biasing upward the apparent impact of nuclear weapons on conventional conflict. Instrumenting for the decision to proliferate, the authors find that nuclear weapons increase diplomatic status without much affecting whether states fight

Different characteristics and nucleotide binding properties of Inosine Monophosphate Dehydrogenase (IMPDH) isoforms

We recently reported that Inosine Monophosphate Dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, clustered into macrostructures in response to decreased nucleotide levels and that there were differences between the IMPDH isoforms, IMPDH1 and IMPDH2. We hypothesised that the Bateman domains, which are present in both isoforms and serve as energy-sensing/allosteric modules in unrelated proteins, would contribute to isoform-specific differences and that mutations situated in and around this domain in IMPDH1 which give rise to retinitis pigmentosa (RP) would compromise regulation. We employed immuno-electron microscopy to investigate the ultrastructure of IMPDH macrostructures and live-cell imaging to follow clustering of an IMPDH2-GFP chimera in real-time. Using a series of IMPDH1/IMPDH2 chimera we demonstrated that the propensity to cluster was conferred by the N-terminal 244 amino acids, which includes the Bateman domain. A protease protection assay suggested isoform-specific purine nucleotide binding characteristics, with ATP protecting IMPDH1 and AMP protecting IMPDH2, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting IMPDH catalytic activity. ATP binding to IMPDH1 was confirmed in a nucleotide binding assay. The RP-causing mutation, R224P, abolished ATP binding and nucleotide protection and this correlated with an altered propensity to cluster. Collectively these data demonstrate that (i) the isoforms are differentially regulated by AMP and ATP by a mechanism involving the Bateman domain, (ii) communication occurs between the Bateman and catalytic domains and (iii) the RP-causing mutations compromise such regulation. These findings support the idea that the IMPDH isoforms are subject to distinct regulation and that regulatory defects contribute to human disease

Childhood studies, children’s politics and participation: perspectives for processes of democratisation

From the early Frankfurt School through to the work of Manuel Castells, there has been a rich body of work on the cleavage between technological and social developments of the twentieth century in respect of the consequences for the constitution of subjectivity. However, little attention is paid to the role of children during their childhoods in attempts to bridge this gap beyond discussions about the democratic actors children will become when they are adults. This paper argues that only the full integration of children, during their childhoods, into democratic development of societies will prevent the deepening of the rift between technological and social progress. The paper traces the correspondence between the new childhood studies and those concepts of politics and politicisation which can support social progress towards an emancipatory social perspective undergirded by particular and democratisation of all areas of everyday life. Drawing on Bourdieu and ideas of participation as action, the paper critically examines the various mechanisms by which children are conventionally excluded from democratic participation and then explores how a deeper consideration of agency in childhood and social actorship opens up alternative mechanisms of inclusion and the concomitant expansion of the concept of democracy