Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis

Supporting Competency Development in Informal Workplace Learning

Abstract. This paper seeks to suggest ways to support informal, self-directed, work-integrated learning within organizations. We focus on a special type of learning in organizations, namely on competency development, that is a purposeful development of employee capabilities to perform well in a large array of situations. As competency development is inherently a self-directed development activity, we seek to support these activities primarily in an informal learning context. AD-HOC environments which allow employees context specific access to documents in a knowledge repository have been suggested to support learning in the workplace. In this paper, we suggest to use the competence performance framework as a means to enhance the capabilities of AD HOC environments to support competency development. The framework formalizes the tasks employees are working in and the competencies needed to perform the tasks. Relating tasks and competencies results in a competence performance structure, which structures both tasks and competencies in terms of learning prerequisites. We conclude with two scenarios that make use o