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Protein trafficking between the cytoplasm and the nucleus is a fundamental process in eukaryotic cell biology. While linear nuclear localization signals (NLSs) are well-characterized, many nuclear proteins lack a predictable NLS. Here, we identify the ETS domain, a DNA-binding winged-helix fold, from ETS family transcription factors as a structure-encoded NLS. We show that ETS domains mediate nuclear import through direct recognition by multiple nuclear transport receptors, including IPO9. Cryo-electron microscopy analysis of the EHF:IPO9 complex reveals that the IPO9 wraps around the ETS domain and engages structural features throughout the winged-helix fold. Biochemical studies demonstrate that the ETS domain DNA-binding helix is critical for importin recognition and for NLS activity in mammalian cells. Comparison of IPO9 bound to EHF and the histone H2A:H2B dimer reveals distinct interaction hotspots, illustrating how IPO9 employs unique combinatorial binding surfaces to accommodate structurally diverse cargos. These findings define a new class of globular NLSs and highlight the adaptability of importins in recognizing distinct protein folds.

The first planetarium projector was completed 100 years ago, providing the public with an unparalleled view of the night sky. The International Planetarium Society is marking this major anniversary with celebratory events across the globe.

Research Methods for Law introduces undergraduate and postgraduate students to available methods of research -- legalistic, empirical, comparative and theoretical -- drawing on actual research projects as examples. The book is written by a team of contributors with a broad range of teaching and research experience in law, criminal justice and socio-legal studies.

This book is a study of the social transformation of criminal justice, its institutions, its method of case disposition and the source of its legitimacy. Focused upon the apprehension, investigation and adjudication of indicted cases in New York City’s main trial tribunal in the nineteenth centuryâ the Court of General Sessions it traces the historical underpinnings of a lawyering culture which, in the first half of the 19th century, celebrated trial by jury as the fairest and most reliable method of case disposition and then at the middle of the century dramatically gave birth to plea bargaining, which thereafter became the dominant method of case disposition in the United States. The book demonstrates that the nature of criminal prosecutions in everyday indicted cases was transformed, from disputes between private parties resolved through a public determination of the facts and law to a private determination of the issues between the state and the individual, marked by greater police involvement in the processing of defendants and public prosecutorial discretion. As this occurred, the structural purpose of criminal courts changed - from individual to aggregate justice - as did the method and manner of their dispositions - from trials to guilty pleas. Contemporaneously, a new criminology emerged, with its origins in European jurisprudence, which was to transform the way in which crime was viewed as a social and political problem. The book, therefore, sheds light on the relationship of the method of case disposition to the means of securing social control of an underclass, in the context of the legitimation of a new social order in which the local state sought to define groups of people as well as actual offending in criminogenic terms. “At a moment when France is poised to adopt plea bargaining, McConville and Mirsky offer the best historical account of its emergence in mid-nineteenth century America, based upon exhaustive analysis of archival data. Their interpretation of the reasons for the dramatic shift from jury trials to negotiated justice offers no comfort for contemporary apologists of plea bargaining as more \"professional.\" The combination of new data and critical reflection on accepted theories make this essential reading for anyone interested in criminal justice policy.” Rick Abel, Connell Professor of Law, UCLA Law School “A fascinating account which traces the origins of plea-bargaining in the politicisation of criminal justice, linking developments in day-to-day practices of the criminal process with macro-changes in political economy, notably the structures of local governance. This is a classic socio-legal study and should be read by anyone interested in criminology, criminal justice, modern history or social theory”. Nicola Lacey, Professor of Criminal Law and Legal Theory, London School of Economics.

In a few weeks in May and June 1944, the future course, of Yugoslavia's history hung in the balance as the Germans attempted to come to terms with Yugoslav Partisan activity by planning the elimination of the Partisan leader, Tito. They were foiled by the work of the British Military Mission in Yugoslavia, who engineered Tito's escape. In this narrative account, Michael McConville describes the background to British involvement with the Partisans, as well as with the Royalist Mihailović. He traces the work of SOE and the decisions which led to the backing of Tito over his rival. McConville highlights the role during the rescue of the costly British Commando diversion on the Island of Brac, which cost, perhaps unnecessarily, over 50 per cent casualties. The author concludes that but for Tito's escape and subsequent return to the fray after two weeks, the future of Yugoslavia, probably under direct Soviet rule, would have been much different.

Disease-causing missense mutations that occur within structurally and functionally unannotated protein regions can guide researchers to new mechanisms of protein regulation and dysfunction. Here, we report that the thrombocytopenia-, myelodysplastic syndromes-, and leukemia-associated P214L mutation in the transcriptional regulator ETV6 creates an XPO1-dependent nuclear export signal to cause protein mislocalization. Strategies to disrupt XPO1 activity fully restore ETV6 P214L protein nuclear localization and transcription regulation activity. Mechanistic insight inspired the design of a 'humanized' ETV6 mice, which we employ to demonstrate that the germline P214L mutation is sufficient to elicit severe defects in thrombopoiesis and hematopoietic stem cell maintenance. Beyond ETV6, we employed computational methods to uncover rare disease-associated missense mutations in unrelated proteins that create a nuclear export signal to disrupt protein function. Thus, missense mutations that operate through this mechanism should be predictable and may suggest rational therapeutic strategies for associated diseases.

Institutional lawyers have increasingly taken over the defence of poor people charged with criminal offences. This paper attempts to explain how and why institutional lawyers arise in a market structured by the state but traditionally dominated by private producers in capitalist societies. The authors use a study of the provision of defence services for poor people in criminal cases in New York City as the basis of their discussion. They stress the vital importance of focusing on the critical relationship between the social organisation of the profession and the nature of the work expected of the lawyer in criminal cases in a capitalist society.