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This Week in PNAS: Apr 21, 2009

Publishing in the online edition last week, research led by Vamsi Mootha and Sarah Calvo at the Broad Institute performed a genome-wide analysis of upstream ORFs and how they affect global protein expression. They looked at 11,649 matched mRNA and protein measurements from four published mammalian studies and selected 25 of them to perform reporter assays on. They estimated that uORFs typically reduce protein expression by 30 to 80 percent, with only a small impact on mRNA levels. After finding 509 polymorphisms that alter uORF presence, they identified five of these that are both linked to diseases and "dramatically silence expression of the downstream protein," they write in the abstract.

A paper from the founder of Oxford Nanopore Technologies, Hagan Bayley, attempts to improve upon nanopore sequencing methods by altering the nanopore. By engineering the biological nanopore α-hemolysin such that the transmembrane β-barrel contains three recognition sites, they were able to distinguish between long strings of A or C bases and identify any of the four bases A, C, G, or T in a random sequence. They point out, though, the the technique only works on immobilized DNA, and the goal is to move the strand over the pore.

Research led in part by James Eberwine delves into the possibilities of transcriptome transfer. In this paper, the team showed that transferring the transcriptome from differentiated rat astrocytes into a nondividing differentiated rat neuron changed the neuron into a functional astrocyte-like cell. "This single-cell study permits high resolution of molecular and functional components that underlie phenotype identity." They used cellular morphology analysis, single-cell PCR, single-cell microarray, and single-cell functional analyses to validate that the astrocyte mRNAs convert 44 percent of the neuronal host cells into the astrocyte-like phenotype.

Finally, there's a review by Stanford's John Ross and Adam Arkin that checks out myriad articles published recently on complex systems. Topics range from information processing in signaling networks to how populations of differentiated cells communicate with each other. "These studies are enabled by the rapid progress in our ability to sequence genomes, measure molecular species and their interactions at genome scale, image their spatial distribution and dynamics during perturbation (at extraordinary resolution), and genetically change the structure of these systems to test theories of function," they say in the article.

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.