Endotoxin, a novel biomarker for the rapid risk assessment of faecal contamination of coastal and transitional waters.

Current methods for testing water for faecal contamination rely on the culture of faecal indicator bacteria (FIB; Escherichia coli and Enterococci) that take 24-48 h, which leads to delays in taking proactive measures and poses a risk to public health. More rapid methods are therefore required. Here, we have tested a rapid, portable assay (Bacterisk) that detects the bacterial biomarker endotoxin in 30 min to quantify the bacterial biomass present, to evaluate 159 coastal water samples and to compare the results with the traditional culture of FIB. There was a significant correlation between the Bacterisk data given in endotoxin risk (ER) units and FIB culture that could accurately distinguish between poor and sufficient or good quality bathing water using the EU bathing directive values. Receiver operating characteristic analysis was used to determine the optimal ER threshold for coastal water samples, and the area under the curve was 0.9176 with a p-value of <0.0001. The optimal threshold was 7,300 ER units with a sensitivity of 95.45% and a specificity of 83.48%. In conclusion, we have shown that the Bacterisk assay provides a rapid and easy-to-use in situ method to assess bathing water quality.

Common genetic variation drives molecular heterogeneity in human iPSCs.

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs.

This corrects the article DOI: 10.1038/nature22403.

Mesoproterozoic surface oxygenation accompanied major sedimentary manganese deposition at 1.4 and 1.1 Ga.

Manganese (Mn) oxidation in marine environments requires oxygen (O2 ) or other reactive oxygen species in the water column, and widespread Mn oxide deposition in ancient sedimentary rocks has long been used as a proxy for oxidation. The oxygenation of Earth's atmosphere and oceans across the Archean-Proterozoic boundary are associated with massive Mn deposits, whereas the interval from 1.8-1.0 Ga is generally believed to be a time of low atmospheric oxygen with an apparent hiatus in sedimentary Mn deposition. Here, we report geochemical and mineralogical analyses from 1.1 Ga manganiferous marine-shelf siltstones from the Bangemall Supergroup, Western Australia, which underlie recently discovered economically significant manganese deposits. Layers bearing Mn carbonate microspheres, comparable with major global Mn deposits, reveal that intense periods of sedimentary Mn deposition occurred in the late Mesoproterozoic. Iron geochemical data suggest anoxic-ferruginous seafloor conditions at the onset of Mn deposition, followed by oxic conditions in the water column as Mn deposition persisted and eventually ceased. These data imply there was spatially widespread surface oxygenation ~1.1 Ga with sufficiently oxic conditions in shelf environments to oxidize marine Mn(II). Comparable large stratiform Mn carbonate deposits also occur in ~1.4 Ga marine siltstones hosted in underlying sedimentary units. These deposits are greater or at least commensurate in scale (tonnage) to those that followed the major oxygenation transitions from the Neoproterozoic. Such a period of sedimentary manganogenesis is inconsistent with a model of persistently low O2 throughout the entirety of the Mesoproterozoic and provides robust evidence for dynamic redox changes in the mid to late Mesoproterozoic.

Screening for modulators of neural network activity in 3D human iPSC-derived cortical spheroids.

Human induced Pluripotent Stem Cells (iPSCs) are a powerful tool to dissect the biology of complex human cell types such as those of the central nervous system (CNS). However, robust, high-throughput platforms for reliably measuring activity in human iPSC-derived neuronal cultures are lacking. Here, we assessed 3D cultures of cortical neurons and astrocytes displaying spontaneous, rhythmic, and highly synchronized neural activity that can be visualized as calcium oscillations on standard high-throughput fluorescent readers as a platform for CNS-based discovery efforts. Spontaneous activity and spheroid structure were highly consistent from well-to-well, reference compounds such as TTX, 4-AP, AP5, and NBQX, had expected effects on neural spontaneous activity, demonstrating the presence of functionally integrated neuronal circuitry. Neurospheroid biology was challenged by screening the LOPAC®1280 library, a collection of 1280 pharmacologically active small molecules. The primary screen identified 111 compounds (8.7%) that modulated neural network activity across a wide range of neural and cellular processes and 16 of 17 compounds chosen for follow-up confirmed the primary screen results. Together, these data demonstrate the suitability and utility of human iPSC-derived neurospheroids as a screening platform for CNS-based drug discovery.