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This Week in PNAS: Aug 10, 2010

In PNAS this week, researchers at Stanford's School of Medicine elucidate the roles of Gqα signaling in C. elegans' regulation of immunity, oxidative stress, and longevity. A signaling module formed by Gqα and its downstream signal transducer phospholipase C β can affect these processes, the authors say. As a result of losing its Gqα and PLCβ functions, C. elegans becomes increasingly sensitive to pathogens and oxidative stress. "We propose a model whereby Gqα signaling differentially regulates pathogen sensitivity, oxidative stress, and longevity through cell autonomous and noncell autonomous effects on p38 MAPK and insulin/IGF1 signaling, respectively," the researchers write.

Also in PNAS this week, researchers at Northwestern University present a "physically grounded" approach for using microarray data to estimate gene expression. McMullen et al. say the difficulties in interpreting microarray data arise from limitations in the data modeling, and propose a "physically motivated" approach for estimating gene expression levels from microarray data by separately modeling the "noises" specific to sample amplification, hybridization, and fluorescence detection. "We find that our model produces estimates of gene expression that are reproducible and unbiased," the authors suggest. "While the details of our model are specific to gene-expression microarrays, we argue that the physically grounded modeling approach we pursue is broadly applicable to other molecular biology technologies."

Researchers at Vanderbilt University present their insights on eukaryotic DNA priming from the structure and functional interactions of the 4FE-4S cluster domain in PNAS this week. By using X-ray crystallography, the researchers were able to map the structure of the C-terminal regulatory domain of the large subunit (p58C) of DNA primase to 1.7-Å resolution, revealing "a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure." Their results, the authors write, explain function defects in human DNA primase mutants and show insight into the regulation of primase activity.

And finally, researchers in California used single-cell mechanics to probe the interactions between amyloid-β peptide and neuronal cells. Using atomic force microscopy-based single-cell compression, Lulevich et al. measured the rigidity of cultured N2a and HT22 neuronal cells as a function of amyloid-β42 protein treatment, and found that Aβ42 oligomers led to significant cellular stiffening. "These findings and measurements provide a deeper, more characteristic, and quantitative insight into interactions between cells and Aβ42 oligomers, which have been considered the prime suspect for initiating neuronal dysfunction in Alzheimer's disease," the authors write.

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.