Centrosome defects cause microcephaly by activating the 53BP1‐USP28‐TP53 mitotic surveillance pathway

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53‐mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53‐mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non‐centrosomal protein SMC5 is also TP53‐dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain.     

An automatically-returned Martian sample by 1985?

The success of the lunar sample analysis programs underscores the desirability of a returned Martian sample. A Mission which would bring back about 1 kg of soil is outlined. The vehicle would have a mass of about 15 tonnes on departure from Earth and would make extensive use of Viking and Mariner technology. Russian experience in the field of automatic soil sampling and automatic rendezvous would be invaluable and the Shuttle would make possible a tidier launch. Sterilisation or quarantine will be necessary to preclude back-contamination of Earth by hypothetical Martian micro-organisms. A prime quarantine facility designed to detect biogenic organic compounds and life processes could be set up at a Lunar base or in a Sky-lab. A single soil sample could be informative as to the general surface composition of Mars. Life detection would be a major task, followed closely by the chemistry of carbon and other life-related elements. However, knowledge of the detailed physics, chemistry and mineralogy of the Martian sample would be of inestimable value to planetary studies.     

Quirks of dye nomenclature. 10. Eosin Y and its close relatives

The long history of eosin Y, eosin B and the methyl and ethyl eosins is recounted as well as their synthesis, the variety of their molecular species and some of the myriad applications of these dyes. Chromatographic techniques are described that reveal the purity or lack of it in commercial samples. Toxicological studies are discussed that suggest that the eosins are virtually non toxic, but efforts to remove them from the environment imply that there may be some risk.