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This Week in PNAS: Mar 1, 2011

In this week's PNAS Early Edition, investigators at the University of Edinburgh in the UK show that "transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer." More specifically, in its investigation of promoter methylation in 19 breast cancer cell lines and 47 primary breast tumors, the team found "120 genes that were significantly repressed in association with methylation," which "allowed the unsupervised segregation of cell lines into epithelial and mesenchymal lineages." The Edinburgh team says that aberrant methylation is a marker for cell lineage rather than for tumor progression.

An international research team this week reports the small molecule antibacterial enoxacin, and its role as a "cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing." Enoxacin, the team shows, promotes the production of miRNAs that act as tumor suppressors in human cell cultures as well as xenografted, orthotopic, and metastatic mouse models.

Researchers at the University of California, San Francisco, along with their international collaborators, report on the role of progranulin gene in neurodegeneration. In a nematode model, the team characterized the typical functions of progranulin; C. elegans mutants lacking the gene that encodes progranulin showed a more rapid clearance of apoptotic cells. "Although most neurodegenerative diseases are thought to be caused by the toxic effects of aggregated proteins, our findings suggest that susceptibility to neurodegeneration may be increased by a change in the kinetics of programmed cell death," the authors write in PNAS.

Also in this week's PNAS, a trio of investigators at Stanford University presents a proteomics-based approach, based on the identification of multiple cargo-binding proteins, to investigate the functions of Drosophila myosin VI. Using mass spec techniques in this manner, the team found "a number of … binding proteins, and further characterization of their interactions with myosin VI will advance our understanding of the roles of these complexes in cellular and developmental processes."

The Scan

Study Points to Tuberculosis Protection by Gaucher Disease Mutation

A mutation linked to Gaucher disease in the Ashkenazi Jewish population appears to boost Mycobacterium tuberculosis resistance in a zebrafish model of the lysosomal storage condition, a new PNAS study finds.

SpliceVault Portal Provides Look at RNA Splicing Changes Linked to Genetic Variants

The portal, described in Nature Genetics, houses variant-related messenger RNA splicing insights drawn from RNA sequencing data in nearly 335,700 samples — a set known as the 300K-RNA resource.

Automated Sequencing Pipeline Appears to Allow Rapid SARS-CoV-2 Lineage Detection in Nevada Study

Researchers in the Journal of Molecular Diagnostics describe and assess a Clear Labs Dx automated workflow, sequencing, and bioinformatic analysis method for quickly identifying SARS-CoV-2 lineages.

UK Team Presents Genetic, Epigenetic Sequencing Method

Using enzymatic DNA preparation steps, researchers in Nature Biotechnology develop a strategy for sequencing DNA, along with 5-methylcytosine and 5-hydroxymethylcytosine, on existing sequencers.