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This Week in Nature: Dec 30, 2010

In Nature this week, researchers at the National Institutes of Health and their international colleagues show that the adaptor protein MYD88 is essential for activated B-cell-like subtype of diffuse large B-cell lymphoma survival. Using RNAi and RNA-seq, the team found mutations in the gene that encodes MYD88 in ABC DLBCL lines, including one amino acid substitution that appeared in 29 percent of the samples, but was "rare or absent in other DLBCL subtypes and Burkitt's lymphoma." Based on the team's subsequent functional analysis, it suggests that "the MYD88 signaling pathway is integral to the pathogenesis of ABC DLBCL."

A research team led by investigators at Harvard Medical School reports in this week's Nature its "comprehensive analysis of the chromatin landscape in Drosophila melanogaster." In summarizing 18 histone modifications by "nine prevalent combinatorial patterns," taken with protein, DNase I hypersensitivity, and GRO-seq data, the Harvard-led team found that "active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts." In addition, the team describes "a diversity of signatures among Polycomb targets" in D. melanogaster.

Investigators at MIT and St. Jude Children's Research Hospital present an RNAi-based approach to characterize small-molecule function in mammalian cells. "By examining the response of cells expressing short hairpin RNAs to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action," the authors write in this week's Nature Chemical Biology. The team used the resulting reference set to predict "mechanisms of action for poorly characterized small molecules." The authors suggest that a "focused shRNA phenotypic signature" is a useful tool for characterizing drug categories.

And in Nature Structural & Molecular Biology, researchers at the Stanford University School of Medicine show that Prdm14 "plays a dual role as a context-dependent transcriptional repressor or activator" in mouse ESCs. The protein "safeguards mESC maintenance by preventing induction of extra-embryonic endoderm fates," the authors write, adding that it accomplishes this by repressing loci that encode ExEn differentiation factors and promoting the expression of genes associated with cell self-renewal.

The Scan

Quality Improvement Study Compares Molecular Tumor Boards, Central Consensus Recommendations

With 50 simulated cancer cases, researchers in JAMA Network Open compared molecular tumor board recommendations with central consensus plans at a dozen centers in Japan.

Lupus Heterogeneity Highlighted With Single-Cell Transcriptomes

Using single-cell RNA sequencing, researchers in Nature Communications tracked down immune and non-immune cell differences between discoid lupus erythematosus and systemic lupus erythematosus.

Rare Disease Clues Gleaned From Mobile Element Insertions in Exome Sequences

With an approach called MELT, researchers in the European Journal of Human Genetics uncovered mobile element insertions in exomes from 3,232 individuals with or without developmental or neurological abnormalities.

Team Tracks Down Potential Blood Plasma Markers Linked to Heart Failure in Atrial Fibrillation Patients

Researchers in BMC Genomics found 10 differentially expressed proteins or metabolites that marked atrial fibrillation with heart failure cases.