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.