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This Week in PNAS: Mar 9, 2010

This week in PNAS, researchers describe their ultrahigh-throughput screening platform that uses drop-based microfluidics to overcome the limitations of traditional methods employed to measure biochemical reactions. The team applied their method ― which uses "aqueous drops dispersed in oil as picoliter-volume reaction vessels" ― to directed evolution; they identified novel mutants of enzymes. In their investigations, the researchers screened 100,000,000 individual enzymatic reactions in only 10 hours, using less than 150 μL of reagent. "We perform the entire assay with a 1,000-fold increase in speed and a 1-million-fold reduction in cost," the authors write.

A pair of researchers from the Yale University School of Medicine report that an Ro protein in Deinococcus radiodurans, a radiaton-resistant eubacterium, participates in ribosomal RNA degradation during the growth in stationary phase ― a time of starvation. Elisabeth Wurtmann and Sandra Wolin suggest that Ro proteins "function as cofactors to increase the association of exonucleases with certain substrates during stress."

Another Yale team reports in PNAS this week that oxidative stress induces protein mistranslation via the impairment of an aminoacyl-tRNA synthetase editing site. Using an Escherichia coli model, the team shows that ― both in vitro and in vivo ― excess reactive oxidative species reduced translational fidelity overall. "The presence of major heat shock proteases was required to allow cell growth in medium containing serine and hydrogen peroxide; this suggests that the mistranslated proteins were misfolded," the authors write.

Also in PNAS this week, researchers in the US and Switzerland describe their confirmation of polypyrimidine tract-binding protein-induced RNA looping using FRET and NMR spectroscopy. The team also affirmed their findings with in vivo splicing data; they show that two PTB RNA recognition motifs can bind two distant pyrimidine tracts, bringing their 5' and 3' ends in close proximity, thus inducing loop formation.

The Scan

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.

Researchers Retrace Key Mutations in Reassorted H1N1 Swine Flu Virus With Avian-Like Features

Mutations in the acidic polymerase-coding gene boost the pathogenicity and transmissibility of Eurasian avian-like H1N1 swine influenza viruses, a PNAS paper finds.

Genome Sequences Reveal Evolutionary History of South America's Canids

An analysis in PNAS of South American canid species' genomes offers a look at their evolutionary history, as well as their relationships and adaptations.

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.