Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Actinide colloids and particles of environmental concern

A study was conducted to investigate actinide colloids and particles of environmental concern. Sources of actinide particles in the environment other than nuclear explosions and nuclear power plant accidents were naturally occurring radioactive matter or particle contaminants released from other military activities related to nuclear power production and from minor occurrences, such as nuclear powered satellites. These particles containing actinide element contaminants were found in the environment in a wide variety of forms or morphologies and compositions, exhibiting varying chemistries and stabilities. The morphology, elemental, and isotopic composition of actinide particles were obtained by a variety of experimental techniques, such as electron microscopy, mass spectrometry (MS), and some other techniques