Cancer cell lines show high heritability for motility but not generation time

Tumour evolution depends on heritable differences between cells in traits affecting cell survival or replication. It is well established that cancer cells are genetically and phenotypically heterogeneous; however, the extent to which this phenotypic variation is heritable is far less well explored. Here, we estimate the broad-sense heritability (H2) of two cell traits related to cancer hallmarks––cell motility and generation time––within populations of four cancer cell lines in vitro and find that motility is strongly heritable. This heritability is stable across multiple cell generations, with heritability values at the high end of those measured for a range of traits in natural populations of animals or plants. These findings confirm a central assumption of cancer evolution, provide a first quantification of the evolvability of key traits in cancer cells and indicate that there is ample raw material for experimental evolution in cancer cell lines. Generation time, a trait directly affecting cell fitness, shows substantially lower values of heritability than cell speed, consistent with its having been under directional selection removing heritable variation

The Labour Government, the Treasury and the £6 pay policy of July 1975

The 1974-79 Labour Government was elected in a climate of opinion that was fiercely opposed to government intervention in the wage determination process, and was committed to the principles of free collective bargaining in its manifestoes. However, by December 1974 the Treasury was advocating a formal incomes policy, and by July 1975 the government had introduced a £6 flat rate pay norm. With reference to archival sources, the paper demonstrates that TUC and Labour Party opposition to incomes policy was reconciled with the Treasury's advocacy by limiting the Bank of England‟s intervention in the foreign exchange market when sterling came under pressure. This both helped to achieve the Treasury's objective of improving the competitiveness of British industry, and acted as a catalyst for the introduction of incomes policy because the slide could be attributed to a lack of market confidence in British counter-inflation policy

Charge Management for Gravitational Wave Observatories using UV LEDs

Accumulation of electrical charge on the end mirrors of gravitational wave observatories, such as the space-based LISA mission and ground-based LIGO detectors, can become a source of noise limiting the sensitivity of such detectors through electronic couplings to nearby surfaces. Torsion balances provide an ideal means for testing gravitational wave technologies due to their high sensitivity to small forces. Our torsion pendulum apparatus consists of a movable Au-coated Cu plate brought near a Au-coated Si plate pendulum suspended from a non-conducting quartz fiber. A UV LED located near the pendulum photoejects electrons from the surface, and a UV LED driven electron gun directs photoelectrons towards the pendulum surface. We have demonstrated both charging and discharging of the pendulum with equivalent charging rates of $\sim$$10^5 e/\mathrm{s}$, as well as spectral measurements of the pendulum charge resulting in a white noise level equivalent to $3\times10^5 e/\sqrt{Hz}$.Comment: 5 pages, submitted to PR

LISA and LISA PathFinder, the endeavour to detect low frequency GWs

This is a review about LISA and its technology demonstrator, LISA PathFinder. We first describe the conceptual problems which need to be overcome in order to set up a working interferometric detector of low frequency Gravitational Waves (GW), then summarise the solutions to them as currently conceived by the LISA mission team. This will show that some of these solutions require new technological abilities which are still under development, and which need proper test before being fully implemented. LISA PathFinder (LPF) is the the testbed for such technologies. The final part of the paper will address the ideas and concepts behind the PathFinder as well as their impact on LISA.Comment: 25 pages, 21 figures, presented at the Spanish Relativity Meeting, Mallorca September 2006. Will be published in Journal of Physics: Conference Series, IOP. To be published in Journal of Physics: Conference Series, IO

Proteomic analysis of Plasmodium in the mosquito: progress and pitfalls

Here we discuss proteomic analyses of whole cell preparations of the mosquito stages of malaria parasite development (i.e. gametocytes, microgamete, ookinete, oocyst and sporozoite) of Plasmodium berghei. We also include critiques of the proteomes of two cell fractions from the purified ookinete, namely the micronemes and cell surface. Whereas we summarise key biological interpretations of the data, we also try to identify key methodological constraints we have met, only some of which we were able to resolve. Recognising the need to translate the potential of current genome sequencing into functional understanding, we report our efforts to develop more powerful combinations of methods for the in silico prediction of protein function and location. We have applied this analysis to the proteome of the male gamete, a cell whose very simple structural organisation facilitated interpretation of data. Some of the in silico predictions made have now been supported by ongoing protein tagging and genetic knockout studies. We hope this discussion may assist future studie

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

Home administration of lanreotide Autogel® by patients with acromegaly, or their partners, is safe and effective

Summary. Objective The introduction of ready-to-use lanreotide Autogel® has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. Design Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel® at their established dose. Effects were monitored for up to 40 weeks. Patients Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel® (60, 90 or 120 mg) for ≥ 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. Results All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%–99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. Conclusions Patients with acromegaly or their partners were able to administer lanreotide Autogel® injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)