July 04, 2016 at 04:52AM

Today I Learned: 1) ...lots of game rules. Learned about Resistance (a variation on Mafia where nobody dies and there's no moderator), Princes of Florence (a hybrid bidding/building placement/action-based, victory-point-scoring German board game about burning money to show off artists and scientists as ornately as possible), and chinese chess (which is surprisingly similar to chess, but with generally weaker pieces, more movement restrictions, and a pretty wacky rule that kings can jump all the way across the board to capture the other king if they have straight line-of-sight). New game rules mostly courtesy of Robert Johnson. 2) A two-inch mantis can't really get through a junebug's armor. Not that it won't try, mind you.... 3) ...a couple of facts about Cas9-based activators in Eukaryotic systems. There was a nice little paper in Nature Methods at the beginning of the year that I finally actually read through today, directly comparing eight different activator variations in a couple of human cell lines(http://ift.tt/29d3r3U, behind a paywall). Three of them worked particularly effectively and robustly: * VPR is a modified version of the standard Cas9-VP64 activator fusion protein (literally just a non-cutting Cas9 fused to the transcriptional activator VP64), with two other activators (I think) tacked onto the VP64 part of the protein. * SAM is another VP64 variant where the guide RNA is modified with some target sequences for an RNA-targeting/gene-activating fusion protein. The combined complex of VP64 and the other gRNA-targeting activator gives SAM a little more oomph, and it looks like SAM was the most robust activator studied in the paper. * SunTag is a system with an aptamer-modified version of dCas9 and a fusion of some antibody fragments (scFV) and VP64. The aptamer fused onto dCas9 consists of 24 repeats of a short peptide sequence that the antibody fragments bind to strongly, bringing VP64 with them, so it's effectively a dCas9 molecule with 24 VP64s attached. Aside from some straightforward characterization stuff, there were a couple of specific interesting points from the paper. Firstly, all of the activators produced the highest fold-change in genes with naturally-low expression, suggesting that there's an inherent limit to how much a gene can turn on, and that strong activation with some of these constructs might bump up against that limit. Secondly, through RNA-seq, the authors could not detect any off-target activation, so these activators are quite specific (which is a little surprising, but nice!). Thirdly, the authors tried making combinations of the three successful activators, but none worked any better than any activator alone. Just how to interpret that is still kind of a question mark.