Tissue-selective expression of a conditionally-active ROCK2-estrogen receptor fusion protein

The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER). This two-stage system of regulation allows for tissue-selective expression of the ROCK2:ER fusion protein, which then requires administration of estrogen analogues such as tamoxifen or 4-hydroxytamoxifen to elicit kinase activity. This conditional gain-of-function system was validated in multiple tissues by crossing with mice expressing CRE recombinase under the transcriptional control of cytokeratin14 (K14), murine mammary tumor virus (MMTV) or cytochrome P450 Cyp1A1 (Ah) promoters, driving appropriate expression in the epidermis, mammary or intestinal epithelia respectively. Given the interest in ROCK signaling in normal physiology and disease, this mouse line will facilitate research into the consequences of ROCK activation that could be used to complement conditional knockout models

A Transiting Jupiter Analog

Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\pm0.02)$ $R_{\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet ($1071.2323\pm0.0006$ d), paving the way for follow-up of this $K=11.8$ mag target.Comment: 14 pages, 10 figures. Accepted to ApJ. Posteriors available at https://github.com/CoolWorlds/Kepler-167-Posterior

Initial Characteristics of Kepler Short Cadence Data

The Kepler Mission offers two options for observations -- either Long Cadence (LC) used for the bulk of core mission science, or Short Cadence (SC) which is used for applications such as asteroseismology of solar-like stars and transit timing measurements of exoplanets where the 1-minute sampling is critical. We discuss the characteristics of SC data obtained in the 33.5-day long Quarter 1 (Q1) observations with Kepler which completed on 15 June 2009. The truly excellent time series precisions are nearly Poisson limited at 11th magnitude providing per-point measurement errors of 200 parts-per-million per minute. For extremely saturated stars near 7th magnitude precisions of 40 ppm are reached, while for background limited measurements at 17th magnitude precisions of 7 mmag are maintained. We note the presence of two additive artifacts, one that generates regularly spaced peaks in frequency, and one that involves additive offsets in the time domain inversely proportional to stellar brightness. The difference between LC and SC sampling is illustrated for transit observations of TrES-2.Comment: 5 pages, 4 figures, ApJ Letters in pres

Protein annotation and modelling servers at University College London

The UCL Bioinformatics Group web portal offers several high quality protein structure prediction and function annotation algorithms including PSIPRED, pGenTHREADER, pDomTHREADER, MEMSAT, MetSite, DISOPRED2, DomPred and FFPred for the prediction of secondary structure, protein fold, protein structural domain, transmembrane helix topology, metal binding sites, regions of protein disorder, protein domain boundaries and protein function, respectively. We also now offer a fully automated 3D modelling pipeline: BioSerf, which performed well in CASP8 and uses a fragment-assembly approach which placed it in the top five servers in the de novo modelling category. The servers are available via the group web site at http://bioinf.cs.ucl.ac.uk/

Detection of gravity modes in the massive binary V380 Cyg from Kepler spacebased photometry and high-resolution spectroscopy

We report the discovery of low-amplitude gravity-mode oscillations in the massive binary star V380 Cyg, from 180 d of Kepler custom-aperture space photometry and 5 months of high-resolution high signal-to-noise spectroscopy. The new data are of unprecedented quality and allowed to improve the orbital and fundamental parameters for this binary. The orbital solution was subtracted from the photometric data and led to the detection of periodic intrinsic variability with frequencies of which some are multiples of the orbital frequency and others are not. Spectral disentangling allowed the detection of line-profile variability in the primary. With our discovery of intrinsic variability interpreted as gravity mode oscillations, V380 Cyg becomes an important laboratory for future seismic tuning of the near-core physics in massive B-type stars.Comment: 5 pages, 4 figures, 2 tables. Accepted for publication in MNRAS Letter

Asteroseismology of the solar analogs 16 Cyg A & B from Kepler observations

The evolved solar-type stars 16 Cyg A & B have long been studied as solar analogs, yielding a glimpse into the future of our own Sun. The orbital period of the binary system is too long to provide meaningful dynamical constraints on the stellar properties, but asteroseismology can help because the stars are among the brightest in the Kepler field. We present an analysis of three months of nearly uninterrupted photometry of 16 Cyg A & B from the Kepler space telescope. We extract a total of 46 and 41 oscillation frequencies for the two components respectively, including a clear detection of octupole (l=3) modes in both stars. We derive the properties of each star independently using the Asteroseismic Modeling Portal, fitting the individual oscillation frequencies and other observational constraints simultaneously. We evaluate the systematic uncertainties from an ensemble of results generated by a variety of stellar evolution codes and fitting methods. The optimal models derived by fitting each component individually yield a common age (t=6.8+/-0.4 Gyr) and initial composition (Z_i=0.024+/-0.002, Y_i=0.25+/-0.01) within the uncertainties, as expected for the components of a binary system, bolstering our confidence in the reliability of asteroseismic techniques. The longer data sets that will ultimately become available will allow future studies of differential rotation, convection zone depths, and long-term changes due to stellar activity cycles.Comment: 6 pages, 2 figures, 2 tables, ApJ Letters (accepted

Protein structure prediction servers at University College London

A number of state-of-the-art protein structure prediction servers have been developed by researchers working in the Bioinformatics Unit at University College London. The popular PSIPRED server allows users to perform secondary structure prediction, transmembrane topology prediction and protein fold recognition. More recent servers include DISOPRED for the prediction of protein dynamic disorder and DomPred for domain boundary prediction. These servers are available from our software home page at

Dynamical masses, absolute radii and 3D orbits of the triply eclipsing star HD 181068 from Kepler photometry

HD 181068 is the brighter of the two known triply eclipsing hierarchical triple stars in the Kepler field. It has been continuously observed for more than 2 yr with the Kepler space telescope. Of the nine quarters of the data, three have been obtained in short-cadence mode, that is one point per 58.9 s. Here we analyse this unique data set to determine absolute physical parameters (most importantly the masses and radii) and full orbital configuration using a sophisticated novel approach. We measure eclipse timing variations (ETVs), which are then combined with the single-lined radial velocity measurements to yield masses in a manner equivalent to double-lined spectroscopic binaries. We have also developed a new light-curve synthesis code that is used to model the triple, mutual eclipses and the effects of the changing tidal field on the stellar surface and the relativistic Doppler beaming. By combining the stellar masses from the ETV study with the simultaneous light-curve analysis we determine the absolute radii of the three stars. Our results indicate that the close and the wide subsystems revolve in almost exactly coplanar and prograde orbits. The newly determined parameters draw a consistent picture of the system with such details that have been beyond reach before