Conserved functional antagonism of CELF 1 and MBNL proteins controls stem cell-specific alternative splicing in planarians

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS in animal stem cell regulation across metazoans

Effect of Multistage Heat Treatment on Microstructure and Mechanical Properties of High-Strength Low-Alloy Steel

The influence of Cu-rich precipitates (CRPs) and reverted austenite (RA) on the strength and impact toughness of a Cu-containing 3.5 wt pct Ni high-strength low-alloy (HSLA) steel after various heat treatments involving quenching (Q), lamellarization (L), and tempering (T) is studied using electron back-scatter diffraction, transmission electron microscopy, and atom probe tomography. The QT sample exhibits high strength but low impact toughness, whereas the QL samples mostly possess improved impact toughness but moderate strength, but the QLT samples again have degraded impact toughness due to additional tempering. The dispersion of nanoscale CRPs, which are formed during tempering, is responsible for the enhanced strength but simultaneously leads to the degraded impact toughness. The RA formed during lamellarization contributes to the improved impact toughness. Based on the present study, new heat treatment schedules are proposed to balance strength and impact toughness by optimizing the precipitation of CRPs and RA. © 2016, The Minerals, Metals Materials Society and ASM International