In PNAS this week, researchers in California and Japan present their study on the transdifferentiation of glioblastoma cells into vascular endothelial cells. In order to assess the glioblastoma resistance mechanism to anti-VEGF therapy, the team examined the vessels of glioblastomas in tumors "induced by the transduction of p53+/− heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase mice." What the researchers were surprised to find were GFP-positive vascular edothelial cells, originating from tumor-initiating cells. The tumor-derived endothelial cells were resistant to an anti-VEGF receptor inhibitor. "We suggest that the [tumor-derived endothelial cell] is an important player in the resistance to anti-VEGF therapy, and hence a potential target for [glioblastoma] therapy," the authors write.
In the PNAS Early Edition this week, researchers in Australia present their findings on a new evolutionary theory that relies on differential dispersal rather than the evolution of traits that facilitate survival or reproduction. "Traits that enhance rates of dispersal inevitably accumulate at expanding range edges, and assortative mating between fast-dispersing individuals at the invasion front results in an evolutionary increase in dispersal rates in successive generations," the authors write. This process generates "novel phenotypes" that are adept at rapid dispersal, no matter how the underlying genes affect an organism's ability to survive or reproduce. "A range of biological phenomena ... may have evolved via spatial sorting as well as (or rather than) by natural selection," the researchers add.
Researchers at Weill Cornell Medical College and the University of Notre Dame report the use of small molecule histone deacetylase inhibitors to reduce cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts. "Some [histone deacetylase] inhibitors lead to a dramatic correction in the NPC phenotype in cells with either one or two copies of the NPC1I1061T mutation, and for several of the inhibitors, correction is associated with increased expression of NPC1 protein," the authors write. Increases in the protein levels may partially account for the correction of the phenotype.
Also in the PNAS Early Edition this week, researchers in Texas and Georgia develop high-throughput image quantification and statistical analysis methods to gain a better understanding of the developmental aggregation dynamics of Myxococcus xanthus. "The analysis shows that small aggregate size but not neighbor-related parameters correlate with aggregate dispersal. Furthermore, close proximity is necessary but not sufficient for aggregate merging," the authors write. "Finally, splitting occurs for those aggregates that are unusually large and elongated." These results show evidence against the role of long-range morphogenic gradients or biased cell exchange in the dispersal, merging, or splitting of transient aggregates, the researchers add.