Identifying Cognate Binding Pairs among a Large Set of Paralogs: The Case of PE/PPE Proteins of Mycobacterium tuberculosis

We consider the problem of how to detect cognate pairs of proteins that bind when each belongs to a large family of paralogs. To illustrate the problem, we have undertaken a genomewide analysis of interactions of members of the PE and PPE protein families of Mycobacterium tuberculosis. Our computational method uses structural information, operon organization, and protein coevolution to infer the interaction of PE and PPE proteins. Some 289 PE/PPE complexes were predicted out of a possible 5,590 PE/PPE pairs genomewide. Thirty-five of these predicted complexes were also found to have correlated mRNA expression, providing additional evidence for these interactions. We show that our method is applicable to other protein families, by analyzing interactions of the Esx family of proteins. Our resulting set of predictions is a starting point for genomewide experimental interaction screens of the PE and PPE families, and our method may be generally useful for detecting interactions of proteins within families having many paralogs

Mental health, citizenship, and the memory of World War II in the Netherlands (1945-85)

After World War II, Dutch psychiatrists and other mental health care professionals articulated ideals of democratic citizenship. Framed in terms of self-development, citizenship took on a broad meaning, not just in terms of political rights and obligations, but also in the context of material, social, psychological and moral conditions that individuals should meet in order to develop themselves and be able to act according to those rights and obligations in a responsible way. In the post-war period of reconstruction (1945-65), as well as between 1965 and 1985, the link between mental health and ideals of citizenship was coloured by the public memory of World War II and the German occupation, albeit in completely different, even opposite ways. The memory of the war, and especially the public consideration of its victims, changed drastically in the mid-1960s, and the mental health sector played a crucial role in bringing this change about. The widespread attention to the mental effects of the war that surfaced in the late 1960s after a period of 20 years of public silence should be seen against the backdrop of the combination of democratization and the emancipation of emotions