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This Week in PNAS: Mar 31, 2009

Steve Carr's group has used quantitative proteomics (SILAC) and affinity enrichment to provide "unbiased, robust and comprehensive identification" of the proteins that bind to small-molecule probes and drugs. They say the method is scalable and general and, in this paper, apply it to identify targets of kinase inhibitors and immunophilin binders.

Harvard and Boston University's Timothy Lu and Jim Collins used synthetic biology techniques to engineer bacteriophages to make bacteria more susceptible to attack by antimicrobial drugs. They show that by suppressing the SOS network in E. coli with engineered bacteriophage, this improves the killing action of quinolones by several orders of magnitude in vitro and increases survival of infected mice in vivo. "This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants," they write.

Two studies use systems biology techniques to study cancers. In one, scientists used bisulfite sequencing to measure passenger methylation at two CpG-rich regions in fragments of 12 colorectal cancers, hoping to glean some insight into how cancer cells grow into tumors. Methylation patterns were consistent with flat clonal expansions and multiple long-lived cancer stem cell lineages per cancer gland. In another paper, researchers looked at genome-wide expression and copy number variation information for primary endometrial cancers to detect which might recur. They found that aggressive tumors were associated with in vitro activation of PI3 kinase.

In early online publication, scientists have used microarray analysis to find a group of genes downstream of Wnt/β-catenin that are directly regulated by Notch, whose activation is important in colorectal cancer. They show that Notch is downstream of Wnt in colorectal cancer cells through β-catenin-mediated transcriptional activation of the Notch-ligand Jagged1.

The Scan

Missed Early Cases

A retrospective analysis of blood samples suggests early SARS-CoV-2 infections may have been missed in the US, the New York Times reports.

Limited Journal Editor Diversity

A survey finds low diversity among scientific and medical journal editors, according to The Scientist.

How Much of a Threat?

Science writes that need for a provision aimed at shoring up genomic data security within a new US bill is being questioned.

PNAS Papers on Historic Helicobacter Spread, Brain Development, C. difficile RNAs

In PNAS this week: Helicobacter genetic diversity gives insight into human migrations, gene expression patterns of brain development, and more.