PedNavigator: a pedigree drawing servlet for large and inbred populations

PedNavigator is a pedigree drawing application for large and complex pedigrees. It has been developed especially for genetic and epidemiological studies of isolated populations characterized by high inbreeding and multiple matrimonies. PedNavigator is written in Java and is intended as a server-side web application, allowing researchers to 'walk' through family ties by point-and-clicking on person's symbols. The application is able to enrich the pedigree drawings with genotypic and phenotypic information taken from the underlying relational database.     

Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2

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Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.Subject terms: Cancer models, Cell biology, Preclinical research