The helicase Ded1p controls use of near-cognate translation initiation codons in 5' UTRs.

The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation1. Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5, and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions

Quantification of Cell Movement Reveals Distinct Edge Motility Types During Cell Spreading

Actin-based motility is central to cellular processes such as migration, bacterial engulfment, and cancer metastasis, and requires precise spatial and temporal regulation of the cytoskeleton. We studied one such process, fibroblast spreading, which involves three temporal phases: early, middle, and late spreading, distinguished by differences in cell area growth. In these studies, aided by improved algorithms for analyzing edge movement, we observed that each phase was dominated by a single, kinematically and biochemically distinct cytoskeletal organization, or motility type. Specifically, early spreading was dominated by periodic blebbing; continuous protrusion occurred predominantly during middle spreading; and periodic contractions were prevalent in late spreading. Further characterization revealed that each motility type exhibited a distinct distribution of the actin-related protein VASP, while inhibition of actin polymerization by cytochalasin D treatment revealed different dependences on barbed-end polymerization. Through this detailed characterization and graded perturbation of the system, we observed that although each temporal phase of spreading was dominated by a single motility type, in general cells exhibited a variety of motility types in neighboring spatial domains of the plasma membrane edge. These observations support a model in which global signals bias local cytoskeletal biochemistry in favor of a particular motility type

An Upper Limit on the Albedo of HD 209458b: Direct Imaging Photometry with the MOST Satellite

We present space-based photometry of the transiting exoplanetary system HD 209458 obtained with the MOST (Microvariablity and Oscillations of STars) satellite, spanning 14 days and covering 4 transits and 4 secondary eclipses. The HD 209458 photometry was obtained in MOST's lower-precision Direct Imaging mode, which is used for targets in the brightness range $6.5 < V < 13$. We describe the photometric reduction techniques for this mode of observing, in particular the corrections for stray Earthshine. We do not detect the secondary eclipse in the MOST data, to a limit in depth of 0.053 mmag (1 \sigma). We set a 1 \sigma upper limit on the planet-star flux ratio of 4.88 x 10^-5 corresponding to a geometric albedo upper limit in the MOST bandpass (400 to 700 nm) of 0.25. The corresponding numbers at the 3 \sigma level are 1.34 x 10^-4 and 0.68 respectively. HD 209458b is half as bright as Jupiter in the MOST bandpass. This low geometric albedo value is an important constraint for theoretical models of the HD209458b atmosphere, in particular ruling out the presence of reflective clouds. A second MOST campaign on HD 209458 is expected to be sensitive to an exoplanet albedo as low as 0.13 (1 sigma), if the star does not become more intrinsically variable in the meantime.Comment: 29 pages, 9 figures. Accepted for publication in the Astrophysical Journal (July 2006, v645n1

Stable Coronal X-Ray Emission Over Twenty Years of XZ Tau

XZ Tau AB is a frequently observed binary YSO in the Taurus Molecular Cloud; XZ Tau B has been classified as an EXOr object. We present new Chandra/HETG-ACIS-S observations of XZ Tau AB, complemented with variability monitoring of the system with XMM-Newton, to constrain the variability of this system and identify high-resolution line diagnostics to better understand the underlying mechanisms that produce the X-rays. We observe two flares with XMM-Newton, but find that outside of these flares the coronal X-ray spectrum of XZ Tau AB is consistent over twenty years of observations. We compare the ensemble of XZ Tau X-ray observations over time with the scatter across stars observed in point-in-time observations of the Orion Nebula Cluster and find that both overlap in terms of plasma properties, i.e., some of the scatter observed in the X-ray properties of stellar ensembles stems from intrinsic source variability.Comment: Accepted for publication in the Astronomical Journal. 19 pages, 11 figure

MOST photometry of the RRd Lyrae variable AQ Leo: Two radial modes, 32 combination frequencies, and beyond

Highly precise and nearly uninterrupted optical photometry of the RR Lyrae star AQ Leo was obtained with the MOST (Microvariability & Oscillations of STars) satellite over 34.4 days in February-March 2005. AQ Leo was the first known double-mode RR Lyrae pulsator (RRd star). Three decades after its discovery, MOST observations have revealed that AQ Leo oscillates with at least 42 frequencies, of which 32 are linear combinations (up to the sixth order) of the radial fundamental mode and its first overtone. Evidence for period changes of these modes is found in the data. The other intrinsic frequencies may represent an additional nonradial pulsation mode and its harmonics (plus linear combinations) which warrant theoretical modeling. The unprecedented number of frequencies detected with amplitudes down to millimag precision also presents an opportunity to test nonlinear theories of mode growth and saturation in RR Lyrae pulsators.Comment: accepted for publication in MNRAS; revision v2 : broken references have been fixe

Non-detection of previously reported transits of HD 97658b with MOST photometry

The radial velocity-discovered exoplanet HD 97658b was recently announced to transit, with a derived planetary radius of 2.93 \pm 0.28 R_{Earth}. As a transiting super-Earth orbiting a bright star, this planet would make an attractive candidate for additional observations, including studies of its atmospheric properties. We present and analyze follow-up photometric observations of the HD 97658 system acquired with the MOST space telescope. Our results show no transit with the depth and ephemeris reported in the announcement paper. For the same ephemeris, we rule out transits for a planet with radius larger than 2.09 R_{Earth}, corresponding to the reported 3\sigma lower limit. We also report new radial velocity measurements which continue to support the existence of an exoplanet with a period of 9.5 days, and obtain improved orbital parameters.Comment: 16 pages, 4 figures; 1 Table; accepted for publication in ApJL, includes changes made in response to the referee repor

QFMatch: multidimensional flow and mass cytometry samples alignment

Part of the flow/mass cytometry data analysis process is aligning (matching) cell subsets between relevant samples. Current methods address this cluster-matching problem in ways that are either computationally expensive, affected by the curse of dimensionality, or fail when population patterns significantly vary between samples. Here, we introduce a quadratic form (QF)-based cluster matching algorithm (QFMatch) that is computationally efficient and accommodates cases where population locations differ significantly (or even disappear or appear) from sample to sample. We demonstrate the effectiveness of QFMatch by evaluating sample datasets from immunology studies. The algorithm is based on a novel multivariate extension of the quadratic form distance for the comparison of flow cytometry data sets. We show that this QF distance has attractive computational and statistical properties that make it well suited for analysis tasks that involve the comparison of flow/mass cytometry samples

Heart and en-bloc thymus transplantation in miniature swine

BackgroundDonor-specific tolerance to organ allografts might be induced by cotransplantation of a sufficient amount of vascularized donor thymus. To facilitate donor thymus-induced cardiac allograft tolerance, we have developed a novel technique for heart and en-bloc thymus transplantation in swine.MethodsDonor heart and en-bloc thymus grafts were prepared by a technique that preserves the entire arterial supply and venous drainage of the right thymic lobe. En-bloc grafts (n = 4) were transplanted heterotopically into the abdomens of major histocompatibility complex-matched miniature swine. Recipients received 12 days of cyclosporine intravenously. Grafts were monitored by palpation, electrocardiographic monitoring, and periodic open biopsy. Engraftment of the donor thymus was demonstrated by measuring the proportion of recipient-type thymocytes in the donor thymus with flow cytometry.ResultsAll of the heart and en-bloc thymus grafts had normal cardiac contractility and immediate perfusion of the thymus. All en-bloc grafts were accepted for more than 200 days without significant acute cellular rejection or cardiac allograft vasculopathy. Thymic tissue of en-bloc grafts displayed normal architecture and supported thymopoiesis of recipient-type cells.ConclusionWe have validated a new technique of donor thymus transplantation that could have utility in human heart transplantation

No Conclusive Evidence for Transits of Proxima b in MOST photometry

The analysis of Proxima Centauri's radial velocities recently led Anglada-Escud\'e et al. (2016) to claim the presence of a low mass planet orbiting the Sun's nearest star once every 11.2 days. Although the a-priori probability that Proxima b transits its parent star is just 1.5%, the potential impact of such a discovery would be considerable. Independent of recent radial velocity efforts, we observed Proxima Centauri for 12.5 days in 2014 and 31 days in 2015 with the MOST space telescope. We report here that we cannot make a compelling case that Proxima b transits in our precise photometric time series. Imposing an informative prior on the period and phase, we do detect a candidate signal with the expected depth. However, perturbing the phase prior across 100 evenly spaced intervals reveals one strong false-positive and one weaker instance. We estimate a false-positive rate of at least a few percent and a much higher false-negative rate of 20-40%, likely caused by the very high flare rate of Proxima Centauri. Comparing our candidate signal to HATSouth ground-based photometry reveals that the signal is somewhat, but not conclusively, disfavored (1-2 sigmas) leading us to argue that the signal is most likely spurious. We expect that infrared photometric follow-up could more conclusively test the existence of this candidate signal, owing to the suppression of flare activity and the impressive infrared brightness of the parent star.Comment: Accepted to ApJ. Posterior samples, MOST photometry and HATSouth photometry are all available at https://github.com/CoolWorlds/Proxim