Richard J. Evans

Direct Voltage Control of Signaling via P2Y1 and Other Gαq-coupled Receptors

Emerging evidence suggests that Ca2+ release evoked by certain G-protein-coupled receptors can be voltage-dependent; however, the relative contribution of different components of the signaling cascade to this response remains unclear. Using the electrically inexcitable megakaryocyte as a model system, we demonstrate that inositol 1,4,5-trisphosphate-dependent Ca2+ mobilization stimulated by several agonists acting via Gαq-coupled receptors is potentiated by depolarization and that this effect is most pronounced for ADP. Voltage-dependent Ca2+ release was not induced by direct elevation of inositol 1,4,5-trisphosphate, by agents mimicking diacylglycerol actions, or by activation of phospholipase Cγ-coupled receptors. The response to voltage did not require voltage-gated Ca2+ channels as it persisted in the presence of nifedipine and was only weakly affected by the holding potential. Strong predepolarizations failed to affect the voltage-dependent Ca2+ increase; thus, an alteration of G-protein βγ subunit binding is also not involved. Megakaryocytes from P2Y1-/- mice lacked voltage-dependent Ca2+ release during the application of ADP but retained this response after stimulation of other Gαq-coupled receptors. Although depolarization enhanced Ca2+ mobilization resulting from GTPγS dialysis and to a lesser extent during \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{AlF}_{4}^{-}\) \end{document} or thimerosal, these effects all required the presence of P2Y1 receptors. Taken together, the voltage dependence to Ca2+ release via Gαq-coupled receptors is not due to control of G-proteins or down-stream signals but, rather, can be explained by a voltage sensitivity at the level of the receptor itself. This effect, which is particularly robust for P2Y1 receptors, has wide-spread implications for cell signaling.

The Feminists : Women's Emancipation Movements in Europe, America and Australasia 1840-1920

Preface 1. Philosophers and Organisers 2. Moderates and Radicals 3. Socialists and Revolutionaries 4. Militants and Conservatives. Conclusion

History, Memory, and the Law: The Historian as Expert Witness

There has been a widespread recovery of public memory of the events of the Second World War since the end of the 1980s, with war crimes trials, restitution actions, monuments and memorials to the victims of Nazism appearing in many countries. This has inevitably involved historians being called upon to act as expert witnesses in legal actions, yet there has been little discussion of the problems that this poses for them. The French historian Henry Rousso has argued that this confuses memory with history. In the aftermath of the Second World War, judicial investigations unearthed a mass of historical documentation. Historians used this, and further researches, from the 1960s onwards to develop their own ideas and interpretations. But since the early 1990s there has been a judicialization of history, in which historians and their work have been forced into the service of moral and legal forms of judgment which are alien to the historical enterprise and do violence to the subleties and nuances of the historian’s search for truth. This reflects Rousso’s perhaps rather simplistically scientistic view of the historian’s enterprise; yet his arguments are powerful and should be taken seriously by any historian considering involvement in a law case; they also have a wider implication for the moralization of the history of the Second World War, which is now dominated by categories such as “perpetrator,”“victim,” and “bystander” that are legal rather than historical in origin. The article concludes by suggesting that while historians who testify in war crimes trials should confine themselves to elucidating the historical context, and not become involved in judging whether an individual was guilty or otherwise of a crime, it remains legitimate to offer expert opinion, as the author of the article has done, in a legal action that turns on the research and writing of history itself.

Redesigning the Past: History in Political Transitions

Redesigning History in Contemporary Russia (Catherine Merridale) History was always an important tool in the hands of Soviet propagandists. All types of historical work were subject to state interference, from school textbooks and encyclopedias to formal historical research and the commemorative use of public space. This article traces the fate of history in Russia through glasnost and the collapse of communism and into the twenty-first century. It discusses the role that history played in current politics, and also the relationship between popular understandings of the past and the formal teaching of history in schools. It argues that history was central to the ideological ferment of the 1980s, but that it has become increasingly marginal, for economic as well as intellectual reasons, as the new Russian state consolidates its position. The argument is made that the decline of history, which some regard as a sign of Russia’s so-called normalization, allows some past injustices to endure, and also permits prejudices to survive unchallenged. Instead of history, today’s Russians — with some conspicuous exceptions — seem to prefer romantic escapism. They are exhausted by political infighting, including morally-charged debates about the recent past. It remains to be seen what price they may pay for turning away from a closer engagement with the painful memories of their grandparents. The Origins of the Two ‘World Wars’: Historical Discourse and International Politics (David Reynolds) It is now almost impossible to imagine the history of the twentieth century without the terms ‘first world war’ and ‘second world war’. Yet using the language of ‘world war’ to describe these two great conflicts was by no means axiomatic. This article on conceptual history concentrates on four principal belligerents — Britain, France, Germany and the USA. It looks first at how the war of 1914–18 was conceptualized at the time, noting the preference in France and particularly Britain for ‘the Great War’, and then examines rethinking during the 1920s and 1930s. It goes on to show how the term ‘second world war’ triumphed during and after the conflict of 1939–45 — though with important exceptions such as China, Japan and the Soviet Union. In both conflicts the leading proponents of ‘world war’ came from Germany and America, and the ultimate triumph of this concept owes much to the ideological battle between Hitler and Roosevelt in 1939–41. The article ends by suggesting that this dominant paradigm may in some respects distort our understanding of modern history. Journal of Contemporary History Copyright

Rethinking German history : nineteenth-century Germany and the origins of the Third Reich

The problem of continuity in modern German history has long been debated by historians, and the search for the origins of Hitlers Third Reich has taken them far back into the German past. Richard J.Evans argues for a social-historical approach and in so doing achieves a rethinking of German history. The book is designed for students of German history and politics; all those interested in contemporary historiography and comparative European history.

Variable inactivation of human factor VIII from different sources by human factor VIII inhibitors

Summary. The source of human factor VIIII (FVIII) had a marked effect on the inhibitory activity of a panel of eight human FVIII inhibitors. Use of conventional FVIII concentrates gave lower inhibitor titres whereas a monoclonal antibody purified FVIII concentrate gave titres similar to or greater than those with plasma. Addition of phospholipid (PL) protected highly purified FVIII against inhibition. The content of PL‐bound FVIII in concentrates may account for the observed differences.

Blood biochemical reference ranges for sows under modern management conditions.

Abstract Published reference ranges for blood biochemistry in swine generally do not relate to sows in modern breeding units, and results were often obtained by methods that are now outdated. The ranges widely used in clinical practice reflect these inappropriate sources. The data presented here were obtained using modern methods of analysis on blood samples from healthy, conventionally managed sows from six breeding herds of known disease status in eastern England, and thus represent appropriate ranges for this class of swine. The values differ from earlier reports principally in higher values for total bilirubin, creatine kinase, and more particularly of total plasma and serum proteins. The latter are shown to be due to higher immunoglobulin concentrations than those previously reported.

Alternative Methods and Their Application in Neurotoxicity Testing

It has been estimated that there are approximately 4–5 million chemical compounds in the environment, with around 50,000–60,000 in common industrial use (1). Up to 1,000 new chemicals enter commerce each year, so it is impossible for populations of living organisms, including man, to avoid exposure to chemicals in some form or another. The existence of this extensive chemical universe, plus the fact that some chemicals are highly toxic to biological systems, emphasises the need to define how chemicals can be safely incorporated into the fabric of modern societies. With regard to neurotoxicants, there is currently an increasing scientific and regulatory awareness of neurotoxicological issues as many more neurologically-important, environmental pollution problems arise; for example, problems involving exposure to lead, aluminium, tin, organic solvents and agrochemicals (2). Moreover, new, potentially centrally-active and neurotoxic xenobiotics are continually entering the development ‘pipeline’ in industry. To identify neurotoxic chemicals and then legislate their use in society, previous and current emphasis is on the use of in vivo methodology. The purpose of this review is to identify the main sources of information on existing in vitro neurotoxicity methods, to highlight some new techniques or concepts, and to indicate key reviews on invertebrate and lower vertebrate neuroscience, since, in theory, some of these simple nervous systems could be exploited for neurotoxicological testing purposes.

A combined deficiency of factor VIII and contact activation defect in a family of cats

The coagulation parameters of a litter of kittens born to an obligate carrier of haemophilia A (classical haemophilia, factor VIII deficiency) are described. Three of four kittens were found to have an intrinsic coagulation defect, but only one was haemophilic. Factor XII deficiency was confirmed in one female, the other female and the dam being carriers of the defect. A confirmed haemophilic male from a previous litter was also found to be a factor XII deficient carrier.

The German unemployed : experiences and consequences of mass unemployment from the Weimar Republic to the Third Reich

How far was unemployment responsible for the triumph of the Third Reich? This collection of essays by British and German historians examines the collapse of democracy in Weimar Germany from the viewpoint of the social historian.