Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions

Oxidation is an important method for the synthesis of chemical intermediates in the manufacture of high-tonnage commodities, high-value fine chemicals, agrochemicals and pharmaceuticals: but oxidations are often inefficient. The introduction of catalytic systems using oxygen from air is preferred for 'green' processing. Gold catalysis is now showing potential in selective redox processes, particularly for alcohol oxidation and the direct synthesis of hydrogen peroxide. However, a major challenge that persists is the synthesis of an epoxide by the direct electrophilic addition of oxygen to an alkene. Although ethene is epoxidized efficiently using molecular oxygen with silver catalysts in a large-scale industrial process, this is unique because higher alkenes can only be effectively epoxidized using hydrogen peroxide, hydroperoxides or stoichiometric oxygen donors. Here we show that nanocrystalline gold catalysts can provide tunable active catalysts for the oxidation of alkenes using air, with exceptionally high selectivity to partial oxidation products ( approximately 98%) and significant conversions. Our finding significantly extends the discovery by Haruta that nanocrystalline gold can epoxidize alkenes when hydrogen is used to activate the molecular oxygen; in our case, no sacrificial reductant is needed. We anticipate that our finding will initiate attempts to understand more fully the mechanism of oxygen activation at gold surfaces, which might lead to commercial exploitation of the high redox activity of gold nanocrystals.     

Lack of substrate specificity on the speed of amoeboid locomotion inNaegleria gruberi

Summary Comparison of locomotory rates ofNaegleria on glass, agar, plastic and fluorocarbon oil under a range of defined electrolyte concentrations showed the speed of amoeboid movement to be independent of the substrate's nature.Acknowledgments. We would like to thank Les Cooper for technical assistance, the Science Research Council for support and the 3M Company for the gift of FC75 oil.     

Linear regression forecasting in the presence of ar(1) disturbances

This paper is concerned with time-series forecasting based on the linear regression model in the presence of AR(1) disturbances. The standard approach is to estimate the AR(1) parameter, ρ, and then construct forecasts assuming the estimated value is the true value. We introduce a new approach which can be viewed as a weighted average of predictions assuming different values of ρ. The weights are proportional to the marginal likelihood of ρ. A Monte Carlo experiment was conducted to compare the new method with five more conventional predictors. Its results suggest that the new approach has a distinct edge over existing procedures.     

The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

Phase transitions in the assembly of multivalent signalling proteins

Cells are organized on length scales ranging from ?ngstr?m to micrometres. However, the mechanisms by which ?ngstr?m-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.     

Inland thinning of West Antarctic Ice Sheet steered along subglacial rifts

Current ice loss from the West Antarctic Ice Sheet (WAIS) accounts for about ten per cent of observed global sea-level rise. Losses are dominated by dynamic thinning, in which forcings by oceanic or atmospheric perturbations to the ice margin lead to an accelerated thinning of ice along the coastline. Although central to improving projections of future ice-sheet contributions to global sea-level rise, the incorporation of dynamic thinning into models has been restricted by lack of knowledge of basal topography and subglacial geology so that the rate and ultimate extent of potential WAIS retreat remains difficult to quantify. Here we report the discovery of a subglacial basin under Ferrigno Ice Stream up to 1.5?kilometres deep that connects the ice-sheet interior to the Bellingshausen Sea margin, and whose existence profoundly affects ice loss. We use a suite of ice-penetrating radar, magnetic and gravity measurements to propose a rift origin for the basin in association with the wider development of the West Antarctic rift system. The Ferrigno rift, overdeepened by glacial erosion, is a conduit which fed a major palaeo-ice stream on the adjacent continental shelf during glacial maxima. The palaeo-ice stream, in turn, eroded the 'Belgica' trough, which today routes warm open-ocean water back to the ice front to reinforce dynamic thinning. We show that dynamic thinning from both the Bellingshausen and Amundsen Sea region is being steered back to the ice-sheet interior along rift basins. We conclude that rift basins that cut across the WAIS margin can rapidly transmit coastally perturbed change inland, thereby promoting ice-sheet instability.     

Structure of epsilon15 bacteriophage reveals genome organization and DNA packaging/injection apparatus

The critical viral components for packaging DNA, recognizing and binding to host cells, and injecting the condensed DNA into the host are organized at a single vertex of many icosahedral viruses. These component structures do not share icosahedral symmetry and cannot be resolved using a conventional icosahedral averaging method. Here we report the structure of the entire infectious Salmonella bacteriophage epsilon15 (ref. 1) determined from single-particle cryo-electron microscopy, without icosahedral averaging. This structure displays not only the icosahedral shell of 60 hexamers and 11 pentamers, but also the non-icosahedral components at one pentameric vertex. The densities at this vertex can be identified as the 12-subunit portal complex sandwiched between an internal cylindrical core and an external tail hub connecting to six projecting trimeric tailspikes. The viral genome is packed as coaxial coils in at least three outer layers with approximately 90 terminal nucleotides extending through the protein core and the portal complex and poised for injection. The shell protein from icosahedral reconstruction at higher resolution exhibits a similar fold to that of other double-stranded DNA viruses including herpesvirus, suggesting a common ancestor among these diverse viruses. The image reconstruction approach should be applicable to studying other biological nanomachines with components of mixed symmetries.     

An RNA gene expressed during cortical development evolved rapidly in humans

The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.