Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro.

Synovial sarcoma is an aggressive soft tissue sarcoma genetically defined by the fusion oncogene SS18-SSX. It is hypothesized that either SS18-SSX disrupts SWI/SNF complex inhibition of the polycomb complex 2 (PRC2) methyltransferase Enhancer of Zeste Homologue 2 (EZH2), or that SS18-SSX is able to directly recruit PRC2 to aberrantly silence target genes. This is of potential therapeutic value as several EZH2 small molecule inhibitors are entering early phase clinical trials. In this study, we first confirmed EZH2 expression in the 76% of human synovial sarcoma samples. We subsequently investigated EZH2 as a therapeutic target in synovial sarcoma in vitro. Knockdown of EZH2 by shRNA or siRNA resulted in inhibition of cell growth and migration across a series of synovial sarcoma cell lines. The EZH2 selective small-molecule inhibitor EPZ005687 similarly suppressed cell proliferation and migration. These data support the hypothesis that targeting EZH2 may be a promising therapeutic strategy in the treatment of synovial sarcoma; clinical trials are initiating enrollment currently

A Possible Massive Asteroid Belt Around zeta Lep

We have used the Keck I telescope to image at 11.7 microns and 17.9 microns the dust emission around zeta Lep, a main sequence A-type star at 21.5 pc from the Sun with an infrared excess. The excess is at most marginally resolved at 17.9 microns. The dust distance from the star is probably less than or equal to 6 AU, although some dust may extend to 9 AU. The mass of observed dust is \~10^22 g. Since the lifetime of dust particles is about 10,000 years because of the Poytning-Robertson effect, we robustly estimate at least 4 10^26 g must reside in parent bodies which may be asteroids if the system is in a steady state and has an age of ~300 Myr. This mass is approximately 200 times that contained within the main asteroid belt in our solar system.Comment: 12 pages, 3 figures, ApJL in pres

Age- and sex-specific response to population density and sex ratio

Both population density and sex ratio shape competition for mates, resources and mating costs. Thus they may critically affect the intensity of sexual selection in the populations. Susceptibility to inter- and intrasexual competition, which changes with age in a large number of species, may additionally influence population response to these demographic factors. In this study, we monitored 16 seminatural populations of common lizards (Lacerta vivipara) to determine whether the reproductive output varied with male and female densities as a function of the individual sex and age. Our results suggest that the intensity of sexual selection was weaker in male-biased populations, supporting new theoretical models. In populations with a male-biased sex ratio, reproductive success was more equally distributed between males and, unlike female-biased populations, the choosiest females (middle-aged) did not obtain sires of higher quality than low-performance females. Our results also suggest that age may influence the intensity of sexual conflict. Middle-aged females (the class with the best performance) produced offspring with a lower body condition in male-biased populations, suggesting that they may be the preferred target of male harassment. By contrast, a male-biased sex ratio appeared to be beneficial for low-quality females, allowing these females to obtain higher quality sires and to produce offspring with a better body condition. These age- and sex-dependent responses to population density and sex ratio have important implications for population ecology and sexual selectio

Globular Cluster Systems and the Missing Satellite Problem: Implications for Cold Dark Matter Models

We analyze the metallicity distributions of globular clusters belonging to 28 early-type galaxies in the survey of Kundu & Whitmore (2001). A Monte Carlo algorithm which simulates the chemical evolution of galaxies that grow hierarchically via dissipationless mergers is used to determine the most probable protogalactic mass function for each galaxy. Contrary to the claims of Kundu & Whitmore, we find that the observed metallicity distributions are in close agreement with the predictions of such hierarchical formation models. The mass spectrum of protogalactic fragments for the galaxies in our sample has a power-law behavior, with an exponent of roughly -2. This spectrum is indistinguishable from the mass spectrum of dark matter halos predicted by cold dark matter models for structure formation. We argue that these protogalactic fragments, the likely sites of globular cluster formation in the early universe, are the disrupted remains of the "missing" satellite galaxies predicted by cold dark matter models. Our findings suggest that the solution to the missing satellite problem is through the suppression of gas accretion in low-mass halos after reionization, or via self-interacting dark matter, and argue against models with suppressed small-scale power or warm dark matter.Comment: 28 pages, 19 postscript figures. Accepted for publication in the Astrophysical Journa

Female common lizards (Lacerta vivipara) do not adjust their sex-biased investment in relation to the adult sex ratio.

Sex allocation theory predicts that facultative maternal investment in the rare sex should be favoured by natural selection when breeders experience predictable variation in adult sex ratios (ASRs). We found significant spatial and predictable interannual changes in local ASRs within a natural population of the common lizard where the mean ASR is female-biased, thus validating the key assumptions of adaptive sex ratio models. We tested for facultative maternal investment in the rare sex during and after an experimental perturbation of the ASR by creating populations with female-biased or male-biased ASR. Mothers did not adjust their clutch sex ratio during or after the ASR perturbation, but produced sons with a higher body condition in male-biased populations. However, this differential sex allocation did not result in growth or survival differences in offspring. Our results thus contradict the predictions of adaptive models and challenge the idea that facultative investment in the rare sex might be a mechanism regulating the population sex ratio

A Parameter Study of Classical Be Star Disk Models Constrained by Optical Interferometry

We have computed theoretical models of circumstellar disks for the classical Be stars $\kappa$ Dra, $\beta$ Psc, and $\upsilon$ Cyg. Models were constructed using a non-LTE radiative transfer code developed by \citet{sig07} which incorporates a number of improvements over previous treatments of the disk thermal structure, including a realistic chemical composition. Our models are constrained by direct comparison with long baseline optical interferometric observations of the H$\alpha$ emitting regions and by contemporaneous H$\alpha$ line profiles. Detailed comparisons of our predictions with H$\alpha$ interferometry and spectroscopy place very tight constraints on the density distributions for these circumstellar disks.Comment: 10 figures,28 pages, accepted by Ap

Quantum degeneracy and interaction effects in spin-polarized Fermi-Bose mixtures

Various features of spin-polarized Fermi gases confined in harmonic traps are discussed, taking into account possible perspectives of experimental measurements. The mechanism of the expansion of the gas is explicitly investigated and compared with the one of an interacting Bose gas. The role of interactions on the equilibrium and non equilibrium behaviour of the fermionic component in Fermi-Bose mixtures is discussed. Special emphasis is given to the case of potassium isotopes mixtures.Comment: 5 pages, 3 figures, revtex, to be published in J. Phys.

The outer halo globular cluster system of M31 - II. Kinematics

We present a detailed kinematic analysis of the outer halo globular cluster (GC) system of M31. Our basis for this is a set of new spectroscopic observations for 78 clusters lying at projected distances between Rproj ~20-140 kpc from the M31 centre. These are largely drawn from the recent PAndAS globular cluster catalogue; 63 of our targets have no previous velocity data. Via a Bayesian maximum likelihood analysis we find that GCs with Rproj > 30 kpc exhibit coherent rotation around the minor optical axis of M31, in the same direction as more centrally- located GCs, but with a smaller amplitude of 86+/-17 km s-1. There is also evidence that the velocity dispersion of the outer halo GC system decreases as a function of projected distance from the M31 centre, and that this relation can be well described by a power law of index ~ -0.5. The velocity dispersion profile of the outer halo GCs is quite similar to that of the halo stars, at least out to the radius up to which there is available information on the stellar kinematics. We detect and discuss various velocity correlations amongst subgroups of GCs that lie on stellar debris streams in the M31 halo. Many of these subgroups are dynamically cold, exhibiting internal velocity dispersions consistent with zero. Simple Monte Carlo experiments imply that such configurations are unlikely to form by chance, adding weight to the notion that a significant fraction of the outer halo GCs in M31 have been accreted alongside their parent dwarf galaxies. We also estimate the M31 mass within 200 kpc via the Tracer Mass Estimator, finding (1.2 - 1.6) +/- 0.2 10^{12}M_sun. This quantity is subject to additional systematic effects due to various limitations of the data, and assumptions built in into the TME. Finally, we discuss our results in the context of formation scenarios for the M31 halo.Comment: 24 pages, 12 figures, 7 tables; Accepted for publication in MNRA