To provide context for the diversification of archosaurs--the group that includes crocodilians, dinosaurs, and birds--we generated draft genomes of three crocodilians: Alligator mississippiensis (the ...American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
We have used asteroseismology to determine fundamental properties for 66 Kepler planet-candidate host stars, with typical uncertainties of 3% and 7% in radius and mass, respectively. The results ...include new asteroseismic solutions for four host stars with confirmed planets (Kepler-4, Kepler-14, Kepler-23 and Kepler-25) and increase the total number of Kepler host stars with asteroseismic solutions to 77. A comparison with stellar properties in the planet-candidate catalog by Batalha et al. shows that radii for subgiants and giants obtained from spectroscopic follow-up are systematically too low by up to a factor of 1.5, while the properties for unevolved stars are in good agreement. We furthermore apply asteroseismology to confirm that a large majority of cool main-sequence hosts are indeed dwarfs and not misclassified giants. Using the revised stellar properties, we recalculate the radii for 107 planet candidates in our sample, and comment on candidates for which the radii change from a previously giant-planet/brown-dwarf/stellar regime to a sub-Jupiter size or vice versa. A comparison of stellar densities from asteroseismology with densities derived from transit models in Batalha et al. assuming circular orbits shows significant disagreement for more than half of the sample due to systematics in the modeled impact parameters or due to planet candidates that may be in eccentric orbits. Finally, we investigate tentative correlations between host-star masses and planet-candidate radii, orbital periods, and multiplicity, but caution that these results may be influenced by the small sample size and detection biases.
MYC is an oncoprotein transcription factor that is overexpressed in the majority of malignancies. The oncogenic potential of MYC stems from its ability to bind regulatory sequences in thousands of ...target genes, which depends on interaction of MYC with its obligate partner, MAX. Here, we show that broad association of MYC with chromatin also depends on interaction with the WD40-repeat protein WDR5. MYC binds WDR5 via an evolutionarily conserved “MYC box IIIb” motif that engages a shallow, hydrophobic cleft on the surface of WDR5. Structure-guided mutations in MYC that disrupt interaction with WDR5 attenuate binding of MYC at ∼80% of its chromosomal locations and disable its ability to promote induced pluripotent stem cell formation and drive tumorigenesis. Our data reveal WDR5 as a key determinant for MYC recruitment to chromatin and uncover a tractable target for the discovery of anticancer therapies against MYC-driven tumors.
Display omitted
•MYC binds directly to the prevalent chromatin regulator WDR5•Interaction with WDR5 is broadly required for MYC to bind chromatin•Mutations that disrupt WDR5 binding perturb MYC-driven cancer and iPSC formation•Properties of the MYC–WDR5 interface make it amenable to small molecule inhibition
MYC is an oncoprotein transcription factor that features prominently in human cancer. Thomas et al. demonstrate that recruitment of MYC to chromatin—and its ability to function as an oncoprotein—depends on its direct interaction with the WD40-repeat protein WDR5.
Population variation in trophic niche is widespread among organisms and is of increasing interest given its role in both speciation and adaptation to changing environments. Trinidadian guppies ...(Poecilia reticulata) inhabiting stream reaches with different predation regimes have rapidly evolved divergent life history traits. Here, we investigated the effects of both predation and resource availability on guppy trophic niches by evaluating their gut contents, resource standing stocks, and δ
N and δ
C stable isotopes across five streams during the wet season. We found that guppies from low predation (LP) sites had a consistently higher trophic position and proportion of invertebrates in their guts and assimilate less epilithon than guppies from high predation (HP) sites. Higher trophic position was also associated with lower benthic invertebrate availability. Our results suggest that LP guppies could be more efficient invertebrate consumers, possibly as an evolutionary response to greater intraspecific competition for higher quality food. This may be intensified by seasonality, as wet season conditions can alter resource availability, feeding rates, and the intensity of intraspecific competition. Understanding how guppy diets vary among communities is critical to elucidating the role of niche shifts in mediating the link between environmental change and the evolution of life histories.
The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial ...(Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described.
A sub-Mercury-sized exoplanet Barclay, Thomas; Rowe, Jason F; Lissauer, Jack J ...
Nature (London),
2013-Feb-28, 2013-02-28, 20130228, Letnik:
494, Številka:
7438
Journal Article
Recenzirano
Odprti dostop
Since the discovery of the first exoplanets, it has been known that other planetary systems can look quite unlike our own. Until fairly recently, we have been able to probe only the upper range of ...the planet size distribution, and, since last year, to detect planets that are the size of Earth or somewhat smaller. Hitherto, no planets have been found that are smaller than those we see in the Solar System. Here we report a planet significantly smaller than Mercury. This tiny planet is the innermost of three that orbit the Sun-like host star, which we have designated Kepler-37. Owing to its extremely small size, similar to that of the Moon, and highly irradiated surface, the planet, Kepler-37b, is probably rocky with no atmosphere or water, similar to Mercury.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted) NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass ...of the innermost planet and revealed a third Jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit, has M sub(P) = ... M sub(+ in circle), R sub(P) = ... R sub(+ in circle), and rho sub(P) = ... g cm super(-3), giving Kepler-68b a density intermediate between that of the ice giants and Earth. Kepler-68c is Earth-sized, with a radius R sub(P) = ... R sub(+ in circle) and transits on a 9.6 day orbit; validation of Kepler-68c posed unique challenges. Kepler-68d has an orbital period of 580 + or - 15 days and a minimum mass of M sub(P) sin i = 0.947 + or - 0.035MJ. Power spectra of the Kepler photometry at one minute cadence exhibit a rich and strong set of asteroseismic pulsation modes enabling detailed analysis of the stellar interior. Spectroscopy of the star coupled with asteroseismic modeling of the multiple pulsation modes yield precise measurements of stellar properties, notably T sub(eff) = 5793 + or - 74 K, Mlow * = 1.079 + or - 0.051 M sub(middot in circle), Rlow * = 1.243 + or - 0.019 R sub(middot in circle), and rholow * = 0.7903 + or - 0.0054 g cm super(-3), all measured with fractional uncertainties of only a few percent. Models of Kepler-68b suggest that it is likely composed of rock and water, or has a H and He envelope to yield its density ~3 g cm super(-3).
It is important to explore the diversity of characteristics of low-mass, low-density planets to understand the nature and evolution of this class of planets. We present a homogeneous analysis of 12 ...new and 9 previously published broad-band photometric observations of the Uranus-sized extrasolar planet GJ 3470b, which belongs to the growing sample of sub-Jovian bodies orbiting M dwarfs. The consistency of our analysis explains some of the discrepancies between previously published results and provides updated constraints on the planetary parameters. Our data are also consistent with previous transit observations of this system. The physical properties of the transiting system can only be constrained as well as the host star is characterized, so we provide new spectroscopic measurements of GJ 3470 from 0.33 to 2.42 μm to aid our analysis. We find R
* = 0.48 ± 0.04 R⊙, M
* = 0.51 ± 0.06 M⊙, and T
eff = 3652 ± 50K for GJ 3470, along with a rotation period of 20.70 ± 0.15 d and an R-band amplitude of 0.01 mag, which is small enough that current transit measurements should not be strongly affected by stellar variability. However, to report definitively whether stellar activity has a significant effect on the light curves, this requires future multiwavelength, multi-epoch studies of GJ 3470. We also present the most precise orbital ephemeris for this system: T
o
= 2455983.70472 ± 0.00021BJDTDB, P = 3.336 6487
$^{+0.000\,0043}_{-0.000\,0033}$
d, and we see no evidence for transit timing variations greater than 1 min. Our reported planet to star radius ratio is 0.076 42 ± 0.000 37. The physical parameters of this planet are R
p = 3.88 ± 0.32 R⊕ and M
p = 13.73 ± 1.61 M⊕. Because of our revised stellar parameters, the planetary radius we present is smaller than previously reported values. We also perform a second analysis of the transmission spectrum of the entire ensemble of transit observations to date, supporting the existence of an H2-dominated atmosphere exhibiting a strong Rayleigh scattering slope.
With the passage of the Deficit Reduction Act of 2005 and the Patient Protection and Affordable Care Act in 2010, Medicare's Inpatient Prospective Payment System (IPPS) began a transition to ...value-based purchasing (VBP) that rewards or penalizes hospitals based on patient satisfaction, clinical processes of care, outcomes, and efficiency metrics. However, hospital-level volatility vs. persistence in value-based payments year-over-year could result in unpredictable cash flows that negatively influence investment behavior, drive underinvestment in community benefit/population health management initiatives, and make management of the factors that drive the VBP adjustment more challenging. To evaluate the volatility and persistence of hospital VBP adjustments, the sample includes VBP adjustments and the associated domain scores for the 2,547 hospitals that participated in the program from 2013 to 2016. The sample includes urban (74%), teaching (29.1%), system affiliated (46.5%), and not-for-profit (63.6%) facilities. Volatility was measured using basic descriptive statistics, relative risk ratios, and a fixed effect, autoregressive, dynamic panel model that robust-clustered the standard errors. There is substantial change in a given facility's total VBP score with an average standard deviation of 10.74 (on a 100-point scale) that is driven by significant volatility in all metrics but particularly by efficiency and outcomes metrics. Relative risk ratios have dropped substantially over the life of the program, and there is low persistence of VBP scores from one period to the next. Findings indicate that if hospitals receive a positive adjustment in 1 year, they are almost as likely to receive a negative adjustment as a positive adjustment the following year. Furthermore, using a fixed-effect dynamic panel model that controls for autocorrelation, we find that only 13.5% of a facility's prior year IPPS adjustment (positive or negative) carries forward to the next year. The low persistence makes investment in population health management and community benefit more challenging.
This article describes the patient-centered Scalable National Network for Effectiveness Research (pSCANNER), which is part of the recently formed PCORnet, a national network composed of learning ...healthcare systems and patient-powered research networks funded by the Patient Centered Outcomes Research Institute (PCORI). It is designed to be a stakeholder-governed federated network that uses a distributed architecture to integrate data from three existing networks covering over 21 million patients in all 50 states: (1) VA Informatics and Computing Infrastructure (VINCI), with data from Veteran Health Administration's 151 inpatient and 909 ambulatory care and community-based outpatient clinics; (2) the University of California Research exchange (UC-ReX) network, with data from UC Davis, Irvine, Los Angeles, San Francisco, and San Diego; and (3) SCANNER, a consortium of UCSD, Tennessee VA, and three federally qualified health systems in the Los Angeles area supplemented with claims and health information exchange data, led by the University of Southern California. Initial use cases will focus on three conditions: (1) congestive heart failure; (2) Kawasaki disease; (3) obesity. Stakeholders, such as patients, clinicians, and health service researchers, will be engaged to prioritize research questions to be answered through the network. We will use a privacy-preserving distributed computation model with synchronous and asynchronous modes. The distributed system will be based on a common data model that allows the construction and evaluation of distributed multivariate models for a variety of statistical analyses.
PDF
