ASD: the Alternative Splicing Database

Alternative splicing is widespread in mammalian gene expression, and variant splice patterns are often specific to different stages of development, particular tissues or a disease state. There is a need to systematically collect data on alternatively spliced exons, introns and splice isoforms, and to annotate this data. The Alternative Splicing Database consortium has been addressing this need, and is committed to maintaining and developing a value-added database of alternative splice events, and of experimentally verified regulatory mechanisms that mediate splice variants. In this paper we present two of the products from this project: namely, a database of computationally delineated alternative splice events as seen in alignments of EST/cDNA sequences with genome sequences, and a database of alternatively spliced exons collected from literature. The reported splice events are from nine different organisms and are annotated for various biological features including expression states and cross-species conservation. The data are presented on our ASD web pages (http://www.ebi.ac.uk/asd).

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration-time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. The associations between tacrolimus trough concentrations (C-0), non-trough concentrations (C-1, C-2, C-4, C-6/8), and AUC(0-12) and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C-0, C-1, C-2, C-4, C-6/8 or AUC(0-12) and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range.

Pathways to human experimentation, 1933-1945: Germany, Japan and the United States

The history of human experimentation in the twelve years between Hitler's rise to power and the end of the Second World War is notorious in the annals of the twen- tieth century. The horrific experiments conducted at Dachau, Auschwitz, Ravens- brueck, Birkenau, and other National Socialist concentration camps reflected an extreme indifference to human life and human suffering. Unfortunately, they do not reflect the extent and complexity of the human experiments undertaken in the years between 1933 and 1945. Following the prosecution of twenty-three high-ranking National Socialist physicians and medical administrators for war crimes and crimes against humanity in the Nuremberg Medical Trial (United States v. Karl Brandt et al.), scholars have rightly focused attention on the nightmarish researches con- ducted by a small group of investigators on concentration camp inmates. Less well known are alternative pathways that brought investigators to undertake human ex- perimentation in other laboratories, settings, and nations.

“Doing” Gender in Context: Household Bargaining and Risk of Divorce in Germany and the United States

Gender relations remain embedded in their sociopolitical context. Compared here using event-history analysis is how household divisions of paid and unpaid labor affect marital stability in the former West Germany, where policy reinforced male breadwinner families, and the United States, where policy remains silent regarding the private sphere. In Germany, any moves away from separate gendered spheres in terms of either wives' relative earnings or husbands' relative participation in housework increase the risk of divorce. In the United States, however, the more stable couples are those that adapt by displaying greater gender equity. These results highlight that policy shapes how gender gets done in the intimate sphere, and that reinforcement of a gendered division of labor may be detrimental to marital stability.