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This Week in PNAS: Oct 20, 2009

In PNAS this week, Stanford University's Sebastian Maerkl and Stephen Quake study the evolution of transcription factors. In this work, they created all possible 95 single-point mutations of five DNA-contacting residues of Max, a human helix–loop–helix transcription factor, and then measured the DNA binding of each mutant. "Our results show that the sequence-specific repertoire of Max accessible through single-point mutations is extremely limited, and we are able to predict 92% of the naturally occurring diversity at these positions," they write.

Researchers led by scientists at Vrije Universiteit in Amsterdam have used multicolor, single-molecule fluorescence imaging to watch DNA unravel. Using a combination of fluorescence microscopy, optical tweezers, and microfluidics, they found that when DNA is overstretched, there is a "gradual conversion from double-stranded to single-stranded DNA, irrespective of the attachment geometry" and that the changes tend to start at nicks or free DNA ends.

Work from scientists at the Max Planck Institute for Developmental Biology have found that "computational design of ligand binding is not a solved problem." In this paper, they looked at the interaction of an arabinose binding protein designed to bind serotonin, finding that in the presence of serotonin, the protein is in an open conformation with no serotonin bound though the side chain conformations are as predicted. In fact, they say, "no indication of binding could be detected for any of the tested designed receptors, whereas wild-type proteins bound their ligands as expected."

Victor Ambros is senior author on work that's discovered a feedback loop involving let-7 family miRNAs and DAF-12 in C. elegans development. The DAF-12 nuclear hormone receptor regulates the transcription of some let-7 family miRNAs and decides between continuous or interrupted development. Here, they report a "complex feedback loop" between DAF-12 and the let-7 family miRNAs, which accounts for "both the repression of DAF-12 by let-7-family miRNAs and the ligand-modulated transcriptional activation and repression of the let-7-Fam miRNAs by DAF-12."

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.