FastML: a web server for probabilistic reconstruction of ancestral sequences

Ancestral sequence reconstruction is essential to a variety of evolutionary studies. Here, we present the FastML web server, a user-friendly tool for the reconstruction of ancestral sequences. FastML implements various novel features that differentiate it from existing tools: (i) FastML uses an indel-coding method, in which each gap, possibly spanning multiples sites, is coded as binary data. FastML then reconstructs ancestral indel states assuming a continuous time Markov process. FastML provides the most likely ancestral sequences, integrating both indels and characters; (ii) FastML accounts for uncertainty in ancestral states: it provides not only the posterior probabilities for each character and indel at each sequence position, but also a sample of ancestral sequences from this posterior distribution, and a list of the k-most likely ancestral sequences; (iii) FastML implements a large array of evolutionary models, which makes it generic and applicable for nucleotide, protein and codon sequences; and (iv) a graphical representation of the results is provided, including, for example, a graphical logo of the inferred ancestral sequences. The utility of FastML is demonstrated by reconstructing ancestral sequences of the Env protein from various HIV-1 subtypes. FastML is freely available for all academic users and is available online at http://fastml.tau.ac.i

Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc

SummaryCCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long-term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization. Cognitive disabilities are associated with downregulation of cadherin and learning-related genes. In addition, CTCF knockdown attenuates fear-conditioning-induced hippocampal gene expression of key learning genes and loss of long-range interactions at the BDNF and Arc loci. This study thus suggests that CTCF-dependent gene expression regulation and genomic organization are regulators of learning and memory

The supine moving apprehension test—Reliability and validity among healthy individuals and patients with anterior shoulder instability

Background: Performance-based tests for patients with anterior shoulder dislocation are lacking. This study determined the reliability and validity of the supine moving apprehension test designed to assess the ability to control anterior instability loads. Methods: Thirty-six participants were recruited (18 healthy individuals, and 18 patients following anterior shoulder dislocation). Healthy participants performed the supine moving apprehension test on 2 separate occasions to determine test-retest reliability. Patients completed the supine moving apprehension test and the Western Ontario Shoulder Instability index before and 6 months after surgical stabilization of their shoulder. The presence of anterior apprehension was also documented post-operatively. Results: The supine moving apprehension test demonstrated good test-retest reliability (intraclass correlation coefficient =0.74−0.84). Patients performed 18−30 repetitions less than healthy individuals during the supine moving apprehension test (P \u3c 0.01). A strong correlation was found between supine moving apprehension test scores and Western Ontario Shoulder Instability post-operatively (r=−0.74, P ≤ 0.01). Supine moving apprehension test scores significantly improved among patients following surgery (P \u3c 0.01). Patients with a negative apprehension test post-operatively performed the supine moving apprehension test significantly better than patients with a positive apprehension test (P \u3c 0.01). Conclusions: The supine moving apprehension test is reliable and valid among patients with anterior shoulder dislocation and may serve to assess patients’ ability to control shoulder anterior instability loads

The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures

ConSurf-DB is a repository for evolutionary conservation analysis of the proteins of known structures in the Protein Data Bank (PDB). Sequence homologues of each of the PDB entries were collected and aligned using standard methods. The evolutionary conservation of each amino acid position in the alignment was calculated using the Rate4Site algorithm, implemented in the ConSurf web server. The algorithm takes into account the phylogenetic relations between the aligned proteins and the stochastic nature of the evolutionary process explicitly. Rate4Site assigns a conservation level for each position in the multiple sequence alignment using an empirical Bayesian inference. Visual inspection of the conservation patterns on the 3D structure often enables the identification of key residues that comprise the functionally important regions of the protein. The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il

Improving PARSEC models for very low mass stars

Many stellar models present difficulties in reproducing basic observational relations of very low mass stars (VLMS), including the mass-radius relation and the optical colour-magnitudes of cool dwarfs. Here, we improve PARSEC (PAdova-TRieste Stellar Evolution Code) models on these points. We implement the T- \ufffd relations from PHOENIX BT-Settl model atmospheres as the outer boundary conditions in the PARSEC code, finding that this change alone reduces the discrepancy in the mass-radius relation from 8 to 5 per cent. We compare the models with multiband photometry of clusters Praesepe and M67, showing that the use of T- \ufffd relations clearly improves the description of the optical colours and magnitudes. But anyway, using both Kurucz and PHOENIX model spectra, model colours are still systematically fainter and bluer than the observations. We then apply a shift to the above T- \ufffd relations, increasing from 0 at Teff = 4730 K to ~14 per cent at Teff = 3160 K, to reproduce the observed mass-radius relation of dwarf stars. Taking this experiment as a calibration of the T- \ufffd relations, we can reproduce the optical and near-infrared colour-magnitude diagrams of low-mass stars in the old metal-poor globular clusters NGC 6397 and 47 Tuc, and in the intermediate-age and young solar-metallicity open clusters M67 and Praesepe. Thus, we extend PARSEC models using this calibration, providing VLMS models more suitable for the lower main-sequence stars over a wide range of metallicities and wavelengths. Both sets of models are available on PARSEC webpage. \ufffd 2014 The Authors

Transiting exoplanets from the CoRoT space mission XXI. CoRoT-19b: A low density planet orbiting an old inactive F9V-star

Observations of transiting extrasolar planets are of key importance to our understanding of planets because their mass, radius, and mass density can be determined. The CoRoT space mission allows us to achieve a very high photometric accuracy. By combining CoRoT data with high-precision radial velocity measurements, we derive precise planetary radii and masses. We report the discovery of CoRoT-19b, a gas-giant planet transiting an old, inactive F9V-type star with a period of four days. After excluding alternative physical configurations mimicking a planetary transit signal, we determine the radius and mass of the planet by combining CoRoT photometry with high-resolution spectroscopy obtained with the echelle spectrographs SOPHIE, HARPS, FIES, and SANDIFORD. To improve the precision of its ephemeris and the epoch, we observed additional transits with the TRAPPIST and Euler telescopes. Using HARPS spectra obtained during the transit, we then determine the projected angle between the spin of the star and the orbit of the planet. We find that the host star of CoRoT-19b is an inactive F9V-type star close to the end of its main-sequence life. The host star has a mass M*=1.21+/-0.05 Msun and radius R*=1.65+/-0.04 Rsun. The planet has a mass of Mp=1.11+/-0.06 Mjup and radius of Rp=1.29+/-0.03 Rjup. The resulting bulk density is only rho=0.71+/-0.06 gcm-3, which is much lower than that for Jupiter. The exoplanet CoRoT-19b is an example of a giant planet of almost the same mass as Jupiter but a 30% larger radius.Comment: 6 pages, 7 figure

A candidate super-Earth planet orbiting near the snow line of Barnard’s star

Barnard’s star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard’s star is also among the least magnetically active red dwarfs known and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging, astrometry and direct imaging, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard’s star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard’s star, making it an excellent target for direct imaging and astrometric observations in the future. © 2018, Springer Nature Limited.The results are based on observations made with the CARMENES instrument at the 3.5-m telescope of the Centro Astronomico Hispano-Aleman de Calar Alto (CAHA, Almeria, Spain), funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de Investigaciones Cientificas (CSIC), the European Union and the CARMENES Consortium members; the 90-cm telescope at the Sierra Nevada Observatory (Granada, Spain) and the 40-cm robotic telescope at the SPACEOBS observatory (San Pedro de Atacama, Chile), both operated by the Instituto de Astrofisica de Andalucia (IAA); and the 80-cm Joan Oro Telescope (TJO) of the Montsec Astronomical Observatory (OAdM), owned by the Generalitat de Catalunya and operated by the Institute of Space Studies of Catalonia (IEEC). This research was supported by the following institutions, grants and fellowships: Spanish MINECO ESP2016-80435-C2-1-R, ESP2016-80435-C2-2-R, AYA2016-79425-C3-1-P, AYA2016-79245-C3-2-P, AYA2016-79425-C3-3-P, AYA2015-69350-C3-2-P, ESP2014-54362-P, AYA2014-56359-P, RYC-2013-14875; Generalitat de Catalunya/CERCA programme; Fondo Europeo de Desarrollo Regional (FEDER); German Science Foundation (DFG) Research Unit FOR2544, project JE 701/3-1; STFC Consolidated Grants ST/P000584/1, ST/P000592/1, ST/M001008/1; NSF AST-0307493; Queen Mary University of London Scholarship; Perren foundation grant; CONICYT-FONDECYT 1161218, 3180405; Swiss National Science Foundation (SNSF); Koshland Foundation and McDonald-Leapman grant; and NASA Hubble Fellowship grant HST-HF2-51399.001. J.T. is a Hubble Fellow