ASXL1 mutations are associated with distinct epigenomic alterations that lead to sensitivity to venetoclax and azacytidine.

The BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1 mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells.

Quantifying ecospace utilization and ecosystem engineering during the early Phanerozoic-The role of bioturbation and bioerosion.

The Cambrian explosion (CE) and the great Ordovician biodiversification event (GOBE) are the two most important radiations in Paleozoic oceans. We quantify the role of bioturbation and bioerosion in ecospace utilization and ecosystem engineering using information from 1367 stratigraphic units. An increase in all diversity metrics is demonstrated for the Ediacaran-Cambrian transition, followed by a decrease in most values during the middle to late Cambrian, and by a more modest increase during the Ordovician.

Chasing Uptake: Super-Resolution Microscopy in Endocytosis and Phagocytosis.

Since their invention about two decades ago, super-resolution microscopes have become a method of choice in cell biology. Owing to a spatial resolution below 50 nm, smaller than the size of most organelles, and an order of magnitude better than the diffraction limit of conventional light microscopes, super-resolution microscopy is a powerful technique for resolving intracellular trafficking. In this review we discuss discoveries in endocytosis and phagocytosis that have been made possible by super-resolution microscopy - from uptake at the plasma membrane, endocytic coat formation, and cytoskeletal rearrangements to endosomal maturation.

Super-resolution Imaging of Structure, Molecular Composition, and Stability of Single Oligonucleotide Polyplexes.

The successful application of gene therapy relies on the development of safe and efficient delivery vectors. Cationic polymers such as cell-penetrating peptides (CPPs) can condense genetic material into nanoscale particles, called polyplexes, and induce cellular uptake. With respect to this point, several aspects of the nanoscale structure of polyplexes have remained elusive because of the difficulty in visualizing the molecular arrangement of the two components with nanometer resolution.