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This Week in PNAS: Jun 19, 2012

In the PNAS Early Edition this week, researchers in New Hampshire and Ohio report that cofactor molecules are an integral part of infectious prions. The team shows that withdrawal of cofactor molecules during serial propagation of purified recombinant prions causes a reduction in specific infectivity and an adaptation of prions containing misfolded proteins. In addition, the team says that if only the cofactor component is changed during serial propagation, major changes in the strain properties of infectious recombinant prions result. "Taken together, these results indicate that cofactor molecules can regulate the defining features of mammalian prions: PrPSc conformation, infectivity, and strain properties," the team adds.

Also in the PNAS Early Edition this week, researchers in the US and Europe describe a widely accessible method for superresolution fluorescence imaging of living systems. The team says its method, called photochromic stochastic optical fluctuation imaging or pcSOFI, irradiates a reversibly photoswitching fluorescent protein at a wavelength that produces "robust single-molecule intensity fluctuations." From this, the researchers can extract a superresolution picture "by a statistical analysis of the fluctuations in each pixel as a function of time." The method requires off-the-shelf equipment, genetically encodable labels, and simple and rapid data acquisition, they say, adding that it is capable of producing "two- to threefold-enhanced spatial resolution, significant background rejection, markedly improved contrast, and favorable temporal resolution in living cells."

An international team of researchers reports that cell crawling mediates collective cell migration to close undamaged epithelial gaps in the PNAS Early Edition. The team developed a pillar stencil approach to create well-defined gaps in an epithelial cell monolayer and found that cells actively respond to pillar removal by extending lamellipodia and moving into the gap created. "In large gaps, closure is dominated by lamellipodium-mediated cell migration," the team writes. "By contrast, closure of gaps smaller than 20 μm was affected by cell density and progressed independently of Rac, myosin light chain kinase, and Rho kinase, suggesting a passive physical mechanism."

Finally, a team led by researchers at Harvard Medical School reports that acetylation helps to regulate RAS oncogenicity. The team determined that RAS is posttranslationally acetylated on lysine 104, and the team then used molecular dynamics simulations to determine that this modification affects the conformational stability of the Switch II domain, which is important for RAS' ability to interact with guanine nucleotide exchange factors. "Consistent with this model, an acetylation-mimetic mutation in K-RAS4B suppressed guanine nucleotide exchange factor-induced nucleotide exchange and inhibited in vitro transforming activity," the team writes. "These data suggest that lysine acetylation is a negative regulatory modification on RAS."

The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.