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This Week in PNAS: Oct 22, 2013

In the early, online edition of the Proceedings of the National Academy of Sciences, investigators from Spain, Germany, and the US describe their search for key somatic mutations and clonal evolution patterns in mantle cell lymphoma. The team tracked down candidate mutations through whole-exome sequencing experiments on matched tumor-normal samples from 29 individuals with MCL and on half a dozen cell lines, along with whole-genome sequencing on samples from four MCL cases. After their follow-up analyses — which included targeted sequencing on samples from 172 more MCL cases — the researchers were left with a set of at least 25 significantly mutated genes. They also uncovered mutations suspected of holding prognostic promise in MCL and began teasing apart MCL subclones within individual patients.

Genomics-based methods can serve as a source of new candidate compounds for modulating memory, according to another PNAS study. A group from Switzerland and Germany performed a SNP-based gene set analysis on 1,802 healthy individuals whose aversive memory performance had been tested as part of a broader assessment of emotional memory-related cognitive abilities. Coupled with replication testing in hundreds more individuals, that analysis led to 20 potential target genes falling in pathways related to neuroactive ligand receptor function and long-term depression. And the researchers' proof-of-principle experiments revealed that compounds interacting with players in the neuroactive ligand receptor gene set did have an impact on aversive memory, suggesting such an approach may be useful for finding memory modulating drugs.

A La Jolla Institute for Allergy and Immunology-led team uncovered a network of microRNAs involved in CD8+ T-cell differentiation following exposure to the cytokine signaling molecule IL-2 and inflammatory signals. Using a combination of RNA sequencing and other experiments in mouse and human cell lines, the researchers homed in on a CD8+ T cell differentiation regulatory network that's mediated by five miRNAs, including miR-139, miR-342, and miR-150. "[O]ur data support the existence of an miRNA-based post-transcriptional program that needs to be shut down or dampened to relive the silence of effectors molecules and ensure proper effector [cytotoxic T lymphocyte] differentiation," the study's authors conclude.