Quantitative perturbation-based analysis of gene expression predicts enhancer activity in early Drosophila embryo.

Enhancers constitute one of the major components of regulatory machinery of metazoans. Although several genome-wide studies have focused on finding and locating enhancers in the genomes, the fundamental principles governing their internal architecture and cis-regulatory grammar remain elusive. Here, we describe an extensive, quantitative perturbation analysis targeting the dorsal-ventral patterning gene regulatory network (GRN) controlled by Drosophila NF-κB homolog Dorsal. To understand transcription factor interactions on enhancers, we employed an ensemble of mathematical models, testing effects of cooperativity, repression, and factor potency. Models trained on the dataset correctly predict activity of evolutionarily divergent regulatory regions, providing insights into spatial relationships between repressor and activator binding sites. Importantly, the collective predictions of sets of models were effective at novel enhancer identification and characterization. Our study demonstrates how experimental dataset and modeling can be effectively combined to provide quantitative insights into cis-regulatory information on a genome-wide scale.

Solid-solution partitioning of plutonium in surface waters at the Atomic Weapons Establishment Aldermaston (UK).

The Atomic Weapons Establishment (AWE) at Aldermaston (Berkshire, UK) has provided and maintained the warheads for the UK's nuclear deterrent for more than 50 years. Whilst the site is radiologically safe, in a few locations the soil contains specific activities of plutonium (Pu) above background arising from a legacy of historic operations. Run-off water (a mixture of rainwater and groundwater) from part of the site is routed into a water management system, and after analysis and radiological assessment, released into local streams. Water and sediment samples have been collected from a number of closely spaced locations within this system to assess the solid-solution partitioning of Pu. Survey work was complemented by batch type desorption experiments to assess redissolution from 'contaminated' sediment into 'uncontaminated' water. The survey data indicate that specific activities of both dissolved and particle bound 239 + 240Pu varied by roughly two orders of magnitude, ranging from approximately 0.7 microBq kg(-1) up to approximately 44 microBq kg(-1), and approximately 1.2 Bq kg(-1) up to approximately 400 Bq kg(-1), respectively, consistent with water originating from different parts of the site. Apparent Kd values varied by an order of magnitude (from 0.7-16 x 10(6)) with an average value of 4 x 10(6). Results from the desorption experiments indicated the extent of redissolution was very small and the derived Kd's corroborated values obtained from the survey work. Kd's given here are compared with other literature values, and are the greatest reported to date. Results are also provided describing the variation in water quality parameters in shallow groundwater samples. Alkalinity values ranged from 120 to 388 mg l(-1) CaCO3 with an average value of 195 mg l(-1) CaCO3. Corresponding values for pH were 6.6-8.3 with an average of 7.5. Over half of the samples were estimated to be supersaturated with respect to calcite. It is suggested that the state of calcite saturation may be responsible for the high Pu Kd. As a consequence of the high particle reactivity, migration of Pu contamination, both within and away from the AWE Aldermaston site, is likely to be very restricted.