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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

Pig Organ Transplants Considered

The Wall Street Journal reports that the US Food and Drug Administration may soon allow clinical trials that involve transplanting pig organs into humans.

'Poo-Bank' Proposal

Harvard Medical School researchers suggest people should bank stool samples when they are young to transplant when they later develop age-related diseases.

Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.