An Enantioselective Artificial Suzukiase Based on the Biotin–Streptavidin Technology

Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee. The hybrid catalyst described herein shows comparable TOF to the previous aqueous-asymmetric Suzuki catalysts, and excellent stability under the reaction conditions to realize higher TON through longer reaction time

Bicontinuous minimal surface nanostructures for polymer blend solar cells

This paper presents the first examination of the potential for bicontinuous structures such as the gyroid structure to produce high efficiency solar cells based on conjugated polymers. The solar cell characteristics are predicted by a simulation model that shows how the morphology influences device performance through integration of all the processes occurring in organic photocells in a specified morphology. In bicontinuous phases, the surface de. ning the interface between the electron and hole transporting phases divides the volume into two disjoint subvolumes. Exciton loss is reduced because the interface at which charge separation occurs permeates the device so excitons have only a short distance to reach the interface. As each of the component phases is connected, charges will be able to reach the electrodes more easily. In simulations of the current-voltage characteristics of organic cells with gyroid, disordered blend and vertical rod (rods normal to the electrodes) morphologies, we find that gyroids have a lower than anticipated performance advantage over disordered blends, and that vertical rods are superior. These results are explored thoroughly, with geminate recombination, i.e. recombination of charges originating from the same exciton, identified as the primary source of loss. Thus, if an appropriate materials choice could reduce geminate recombination, gyroids show great promise for future research and applications

How do cities approach policy innovation and policy learning? A study of 30 policies in Northern Europe and North America

This paper reports on a study of current practice in policy transfer, and ways in which its effectiveness can be increased. A literature review identifies important factors in examining the transfer of policies. Results of interviews in eleven cities in Northern Europe and North America investigate these factors further. The principal motivations for policy transfer were strategic need and curiosity. Local officials and politicians dominated the process of initiating policy transfer, and local officials were also the leading players in transferring experience. A range of information sources are used in the search process but human interaction was the most important source of learning for two main reasons. First, there is too much information available through the Internet and the search techniques are not seen to be wholly effective in identifying the necessary information. Secondly, the information available on websites, portals and even good practice guides is not seen to be of mixed quality with risks of focussing only on successful implementation and therefore subject to some bias. Officials therefore rely on their trusted networks of peers for lessons as here they can access the ‘real implementation’ story and the unwritten lessons. Organisations which have a culture that is supportive of learning from elsewhere had strong and broad networks of external contacts and resourced their development whilst others are more insular or inward looking and reluctant to invest in policy lessons from elsewhere. Solutions to the problems identified in the evidence base are proposed

Membrane-Protein Interactions in a Generic Coarse-Grained Model for Lipid Bilayers

We study membrane-protein interactions and membrane-mediated protein-protein interactions by Monte Carlo simulations of a generic coarse-grained model for lipid bilayers with cylindrical hydrophobic inclusions. The strength of the hydrophobic force and the hydrophobic thickness of the proteins are systematically varied. The results are compared with analytical predictions of two popular analytical theories: The Landau-de Gennes theory and the elastic theory. The elastic theory provides an excellent description of the fluctuation spectra of pure membranes and successfully reproduces the deformation profiles of membranes around single proteins. However, its prediction for the potential of mean force between proteins is not compatible with the simulation data for large distances. The simulations show that the lipid-mediated interactions are governed by five competing factors: Direct interactions, lipid-induced depletion interactions, lipid bridging, lipid packing, and a smooth long-range contribution. The mechanisms leading to "hydrophobic mismatch" interactions are critically analyzed.Comment: 16 pages, 8 figures, accepted for publication in Biophysical Journa

The water quality of the River Enborne, UK: observations from high-frequency Monitoring in a rural, lowland river system

This paper reports the results of a 2-year study of water quality in the River Enborne, a rural river in lowland England. Concentrations of nitrogen and phosphorus species and other chemical determinands were monitored both at high-frequency (hourly), using automated in situ instrumentation, and by manual weekly sampling and laboratory analysis. The catchment land use is largely agricultural, with a population density of 123 persons km−2. The river water is largely derived from calcareous groundwater, and there are high nitrogen and phosphorus concentrations. Agricultural fertiliser is the dominant source of annual loads of both nitrogen and phosphorus. However, the data show that sewage effluent discharges have a disproportionate effect on the river nitrogen and phosphorus dynamics. At least 38% of the catchment population use septic tank systems, but the effects are hard to quantify as only 6% are officially registered, and the characteristics of the others are unknown. Only 4% of the phosphorus input and 9% of the nitrogen input is exported from the catchment by the river, highlighting the importance of catchment process understanding in predicting nutrient concentrations. High-frequency monitoring will be a key to developing this vital process understanding

NH125 Sensitizes Staphylococcus aureus to Cell Wall-Targeting Antibiotics through the Inhibition of the VraS Sensor Histidine Kinase

Staphylococcus aureus utilizes the two-component regulatory system VraSR to receive and relay environmental stress signals, and it is implicated in the development of bacterial resistance to several antibiotics through the upregulation of cell wall synthesis. VraS inhibition was shown to extend or restore the efficacy of several clinically used antibiotics. In this work, we study the enzymatic activity of the VraS intracellular domain (GST-VraS) to determine the kinetic parameters of the ATPase reaction and characterize the inhibition of NH125 under in vitro and microbiological settings. The rate of the autophosphorylation reaction was determined at different GST-VraS concentrations (0.95 to 9.49 μM) and temperatures (22 to 40°C) as well as in the presence of different divalent cations. The activity and inhibition by NH125, which is a known kinase inhibitor, were assessed in the presence and absence of the binding partner, VraR. The effects of inhibition on the bacterial growth kinetics and gene expression levels were determined. The GST-VraS rate of autophosphorylation increases with temperature and with the addition of VraR, with magnesium being the preferred divalent cation for the metal-ATP substrate complex. The mechanism of inhibition of NH125 was noncompetitive in nature and was attenuated in the presence of VraR. The addition of NH125 in the presence of sublethal doses of the cell wall-targeting antibiotics carbenicillin and vancomycin led to the complete abrogation of Staphylococcus aureus Newman strain growth and significantly decreased the gene expression levels of pbpB, blaZ, and vraSR in the presence of the antibiotics

ATP half-sites in RadA and RAD51 recombinases bind nucleotides.

Homologous recombination is essential for repair of DNA double-strand breaks. Central to this process is a family of recombinases, including archeal RadA and human RAD51, which form nucleoprotein filaments on damaged single-stranded DNA ends and facilitate their ATP-dependent repair. ATP binding and hydrolysis are dependent on the formation of a nucleoprotein filament comprising RadA/RAD51 and single-stranded DNA, with ATP bound between adjacent protomers. We demonstrate that truncated, monomeric Pyrococcus furiosus RadA and monomerised human RAD51 retain the ability to bind ATP and other nucleotides with high affinity. We present crystal structures of both apo and nucleotide-bound forms of monomeric RadA. These structures reveal that while phosphate groups are tightly bound, RadA presents a shallow, poorly defined binding surface for the nitrogenous bases of nucleotides. We suggest that RadA monomers would be constitutively bound to nucleotides in the cell and that the bound nucleotide might play a structural role in filament assembly.We would like to thank Dr Timothy Sharpe for help with MALS analysis of the monomeric RadA protein and Dr Tara Pukala for the mass spectrometric analysis of the same protein. We would like to thank X-ray crystallographic and Biophysics facilities at the Department of Biochemistry for access to their instrumentation. We thank Diamond Light Source for access to beamline I04 (proposal MX315), European Synchrotron Radiation Facility for access to beamline ID23-1 (proposal MX-705 17 and MX-857) and Swiss Light Source for access to beamline PXIII that contributed to the results presented here. This work was funded by Translational Award from the Wellcome Trust (080083/Z/06/Z).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley

Glycoprotein B switches conformation during murid herpesvirus 4 entry

Herpesviruses are ancient pathogens that infect all vertebrates. The most conserved component of their entry machinery is glycoprotein B (gB), yet how gB functions is unclear. A striking feature of the murid herpesvirus 4 (MuHV-4) gB is its resistance to neutralization. Here, we show by direct visualization of infected cells that the MuHV-4 gB changes its conformation between extracellular virions and those in late endosomes, where capsids are released. Specifically, epitopes on its N-terminal cell-binding domain become inaccessible, whilst non-N-terminal epitopes are revealed, consistent with structural changes reported for the vesicular stomatitis virus glycoprotein G. Inhibitors of endosomal acidification blocked the gB conformation switch. They also blocked capsid release and the establishment of infection, implying that the gB switch is a key step in entry. Neutralizing antibodies could only partially inhibit the switch. Their need to engage a less vulnerable, upstream form of gB, because its fusion form is revealed only in endosomes, helps to explain why gB-directed MuHV-4 neutralization is so difficult

The Evolution of Cool Algols

We apply a model of dynamo-driven mass loss, magnetic braking and tidal friction to the evolution of stars with cool convective envelopes; in particular we apply it to binary stars where the combination of magnetic braking and tidal friction can cause angular-momentum loss from the {\it orbit}. For the present we consider the simplification that only one component of a binary is subject to these non-conservative effects, but we emphasise the need in some circumstances to permit such effects in {\it both} components. The model is applied to examples of (i) the Sun, (ii) BY Dra binaries, (iii) Am binaries, (iv) RS CVn binaries, (v) Algols, (vi) post-Algols. A number of problems regarding some of these systems appear to find a natural explanation in our model. There are indications from other systems that some coefficients in our model may vary by a factor of 2 or so from system to system; this may be a result of the chaotic nature of dynamo activity

Discovery of Samarium, Europium, Gadolinium, and Terbium Isotopes

Currently, thirty-four samarium, thirty-four europium, thirty-one gadolinium, and thirty-one terbium isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.Comment: To be published in At. Data Nucl. Data Table