Method for suppressing non-specific protein interactions observed with affinity resins.

Previous high throughput data analysis from several different approaches to affinity purification of protein complexes have revealed catalogues of contaminating proteins that persistently co-purify. Some of these contaminating proteins appear to be specific to one particular affinity matrix used or even to the artificial affinity tags introduced into endogenous proteins for the purpose of purification. A recent approach to minimising non-specific protein interactions in high throughput screens utilises pre-equilibration of affinity surfaces with thiocyanate anions to reduce non-specific binding of proteins. This approach not only reduces the effect of contaminating proteins but also promotes the enrichment of the specific binding partners. Here, we have taken this method and adapted it in an attempt to reduce the abundance of common contaminants in affinity purification experiments. We found the effect varied depending on the bait used, most likely due to its endogenous abundance.This work was funded by the Wellcome Trust grant 076739/Z/05/Z.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ymeth.2011.06.00

The Genomics of Human Local Adaptation

Modern humans inhabit a variety of environments and are exposed to a plethora of selective pressures, leading to multiple genetic adaptations to local environmental conditions. These include adaptations to climate, UV exposure, disease, diet, altitude, or cultural practice and have generated important genetic and phenotypic differences amongst populations. In recent years, new methods to identify the genomic signatures of natural selection underlying these adaptations, combined with novel types of genetic data (e.g., ancient DNA), have provided unprecedented insights into the origin of adaptive alleles and the modes of adaptation. As a result, numerous instances of local adaptation have been identified in humans. Here, we review the most exciting recent developments and discuss, in our view, the future of this field

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.The authors are very grateful to the Medical Research Council and Action Medical Research for financial support.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2015.09.02

Magnetoencephalographic Correlates of Perceptual State During Auditory Bistability

Bistability occurs when two alternative percepts can be derived from the same physical stimulus. To identify the neural correlates of specifc subjective experiences we used a bistable auditory stimulus and determined whether the two perceptual states could be distinguished electrophysiologically. Fourteen participants underwent magnetoencephalography while reporting their perceptual experience while listening to a continuous bistable stream of auditory tones. Participants reported bistability with a similar overall proportion of the two alternative percepts (52% vs 48%). At the individual level, sensor space electrophysiological discrimination between the percepts was possible in 9/14 participants with canonical variate analysis (CVA) or linear support vector machine (SVM) analysis over space and time dimensions. Classifcation was possible in 14/14 subjects with non-linear SVM. Similar efects were noted in an unconstrained source space CVA analysis (classifying 10/14 participants), linear SVM (classifying 9/14 subjects) and non-linear SVM (classifying 13/14 participants). Source space analysis restricted to a priori ROIs showed discrimination was possible in the right and left auditory cortex with each classifcation approach but in the right intraparietal sulcus this was only apparent with non-linear SVM and only in a minority of particpants. Magnetoencephalography can be used to objectively classify auditory experiences from individual subjects

What do γ\gamma-ray bursts look like?

There have been great and rapid progresses in the field of $\gamma$-ray bursts (denoted as GRBs) since BeppoSAX and other telescopes discovered their afterglows in 1997. Here, we will first give a brief review on the observational facts of GRBs and direct understanding from these facts, which lead to the standard fireball model. The dynamical evolution of the fireball is discussed, especially a generic model is proposed to describe the whole dynamical evolution of GRB remnant from highly radiative to adiabatic, and from ultra-relativistic to non-relativistic phase. Then, Various deviations from the standard model are discussed to give new information about GRBs and their environment. In order to relax the energy crisis, the beaming effects and their possible observational evidences are also discussed in GRB's radiations.Comment: 10 pages, Latex. Invited talk at the Pacific Rim Conference on Stellar Astrophysics, Hong Kong, China, Aug. 199

The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype).

Sickle cell disease (SCD) is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12-15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC) constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs), containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.Peer Reviewe

Binary Population Synthesis: Methods, Normalization, and Surprises

In this paper we present a brief overview of population synthesis methods with a discussion of their main advantages and disadvantages. In the second part, we present some recent results from synthesis models of close binary compact objects with emphasis on the predicted rates, their uncertainties, and the model input parameters the rates are most sensitive to. We also report on a new evolutionary path leading to the formation of close double neutron stars (NS), with the unique characteristic that none of the two NS ever had the chance to be recycled by accretion. Their formation rates turn out to be comparable to or maybe even higher than those of recycled NS-NS binaries (like the ones observed), but their detection probability as binary pulsars is much smaller because of their short lifetimes. We discuss the implications of such a population for gravitational-wave detection of NS-NS inspiral events, and possibly for gamma-ray bursts and their host galaxies.Comment: 15 pages, 1 figure, to appear in the proceedings ``The influence of binaries on stellar population studies'', Brussels, August 2000 (Kluwer Academic Publishers), ed. D.Vanbevere

A direct image of the obscuring disk surrounding an active galactic nucleus

Active galactic nuclei (AGN) are generally accepted to be powered by the release of gravitational energy in a compact accretion disk surrounding a massive black hole. Such disks are also necessary to collimate powerful radio jets seen in some AGN. The unifying classification schemes for AGN further propose that differences in their appearance can be attributed to the opacity of the accreting material, which may obstruct our view of the central region of some systems. The popular model for the obscuring medium is a parsec-scale disk of dense molecular gas, although evidence for such disks has been mostly indirect, as their angular size is much smaller than the resolution of conventional telescopes. Here we report the first direct images of a pc-scale disk of ionised gas within the nucleus of NGC 1068, the archetype of obscured AGN. The disk is viewed nearly edge-on, and individual clouds within the ionised disk are opaque to high-energy radiation, consistent with the unifying classification scheme. In projection, the disk and AGN axes align, from which we infer that the ionised gas disk traces the outer regions of the long-sought inner accretion disk.Comment: 14 pages, LaTeX, PSfig, to appear in Nature. also available at http://hethp.mpe-garching.mpg.de/Preprint

An unfolding signifier: London's Baltic Exchange in Tallinn

In the summer of 2007 an unusual cargo arrived at Muuga and Paldiski harbors outside Tallinn. It consisted of nearly 50 containers holding over 1,000 tons of building material ranging from marble columns, staircases and fireplaces, to sculpted allegorical figures, wooden paneling and old-fashioned telephone booths. They were once part of the Baltic Exchange in the City of London. Soon they will become facets of the landscape of Tallinn. The following article charts this remarkable story and deploys this fragmented monument to analyze three issues relating to the Estonian capital: the relocation of the ‘Bronze Soldier’, the demolition of the Sakala Culture Center, and Tallinn’s future role as European Cultural Capital in 2011