In a paper published online in advance in the PNAS Early Edition this week, a team led by investigators at Harvard Medical School shows that, in a mouse model of pancreatic neuorendocrine cancer, administration of the endogenous angiogenesis inhibitors endostatin, thrombospondin-1, and tumstatin peptides, "as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors." Further, the team reports its finding that the deletion of tumstatin and thrombospondin-1 in mice lacking the p53 gene show an "increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival." Overall, the team says its study shows that endogenous angiogenesis inhibitors serve as "intrinsic microenvironmental barriers to tumorigenesis."
In another PNAS Early Edition paper, Harvard University's Scott Wylie and Eugene Shakhnovich used population genetics simulations and a "simple biophysical protein-folding model" to find that "in mutation/selection/drift steady state, high mutation rates lead to less stable proteins and a more dispersed DFE [distribution of fitness effects]." The team also reports that its model showed that "small population size also decreases stability and robustness." Overall, Wylie and Shakhnovich say that "compensatory mutations are common in small populations with high mutation rates" and that an "interplay between biophysical and population genetic forces shapes the DFE."
The Wellcome Trust Centre for Cell Biology's Grzegorz Kudla et al. show that "cross-linking, ligation, and sequencing of hybrids," or CLASH, "reveals RNA–RNA interactions in yeast." Using CLASH, the team "identified 39 known target sites for box C/D modification-guide small nucleolar RNAs on the yeast pre-rRNA," and says that its approach "should allow transcriptome-wide analyses of RNA–RNA interactions in many organisms."