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This Week in PNAS: Aug 11, 2009

In the early online edition of PNAS, scientists from Imperial College London and Pfizer report a successful application of metabolic profiling. Using NMR to profile the urine of 99 men who were given acetaminophen, they found that those with higher initial levels of p-cresol sulfate metabolized the drug less effectively than those with lower levels. "Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach," they say in the abstract. GenomeWeb Daily News has the full scoop.

In another paper, scientists led by Eshel Ben-Jacob of Tel Aviv University and UCSD used antigen microarrays to profile the makeup of autoantibodies – antibodies that bind to self molecules – in newborns. Using an antigen microarray containing hundreds of self molecules, they found among other things that mothers and young adults had more organization to the different types of antibodies. "These findings suggest that the natural autoantibody repertoire of humans shows relatively little organization at birth, but, by young adulthood, it becomes sorted out into a modular organization of subgroups (cliques) of correlated antigens," they write in the abstract.

At the Nijmegen Centre for Molecular Life Sciences, Susan Mulders was first author on work that successfully used an antisense oligonucleotide to counteract RNA toxicity in myotonic dystrophy. Myotonic dystrophy type 1 is caused by a triplet repeat in DM protein kinase (DMPK) transcripts, they say. Their experiment found an antisense oligo that could silence mutant DMPK RNA expression and lower the level of toxic RNA.

And last week, researchers used computational design to develop peptides that could target specific molecules through helix-helix interactions, reducing their effect. They designed peptides that targeted gp96 and clusterin, two secreted chaperones known to affect signaling cascades through conformational changes. Testing the gp96-derived peptide in human blood mononuclear cells, they found that it inhibited the production of TNFα, IL-1β, IL-6, and IL-8 by more than 80 percent; and when they injected it into mice, the peptide lowered circulating levels of TNFα, IL-6, and IFNγ by greater than 50 percent. The clusterin-targeting peptide stopped proliferation of several neoplastic cell lines.

The Scan

Billions for Antivirals

The US is putting $3.2 billion toward a program to develop antivirals to treat COVID-19 in its early stages, the Wall Street Journal reports.

NFT of the Web

Tim Berners-Lee, who developed the World Wide Web, is auctioning its original source code as a non-fungible token, Reuters reports.

23andMe on the Nasdaq

23andMe's shares rose more than 20 percent following its merger with a special purpose acquisition company, as GenomeWeb has reported.

Science Papers Present GWAS of Brain Structure, System for Controlled Gene Transfer

In Science this week: genome-wide association study ties variants to white matter stricture in the brain, and more.