Generating Shigella that internalize into glioblastoma cells

IntroductionThe use of microorganisms as drug delivery systems to treat cancer has expanded recently, including FDA approval of certain viruses as oncolytics. Microorganisms have several unique benefits compared to traditional pharmacologic agents including dose independence, the ability to produce therapeutic proteins locally within the tumor, and simplicity of administration. However, current microbial delivery systems such as AAV9 and herpes virus have limited cassette sizes, minimal cancer cell selectivity, and low innate cytotoxicity. To address these issues, we sought to generate a strain of Shigella flexneri to selectively internalize into glioblastoma (GBM) brain tumor cells as an initial step to generating a bacterial-based drug delivery system.MethodsWe generated S. flexneri that selectively internalize into GBM cells using iterative co-cultured assays.ResultsAfter 50 rounds of co-culture, the new strain infected 95 percent of GBM cells in 2 hours. GBM-infecting Shigella demonstrate a 124-fold preference for internalizing in nine different GBM cell lines compared to Normal Astrocytes (NA) controls. Additionally, we developed an in-cell western to identify GBM-infecting Shigella clones that preferentially internalize in patient samples without iterative co-culture. Finally, we demonstrate internalization into GBM cells is mediated via a factor modified by myristoylation.DiscussionIn conclusion, here we present a novel bacterial platform that preferentially internalizes in brain tumor cells. This system provides numerous potential benefits over current interventions and other microbial strategies for treating brain tumors

SAURON Observations of Disks in Early-Type Galaxies

We briefly describe the SAURON project, aimed at determining the intrinsic shape and internal dynamics of spheroids. We focus here on the ability of SAURON to identify gaseous and stellar disks and to measure their morphology and kinematics. We illustrate some of our results with complete maps of NGC3377, NGC3623, and NGC4365.Comment: 4 pages, 4 figures (newpasp.sty). To appear in ASP Conf. Series "Galaxy Disks and Disk Galaxies", eds. J.G. Funes S.J. & E.M. Corsini. Version with full resolution images available at http://www.strw.leidenuniv.nl/~bureau/pub_list.htm

Dynamical Friction in dE Globular Cluster Systems

The dynamical friction timescale for globular clusters to sink to the center of a dwarf elliptical galaxy (dE) is significantly less than a Hubble time if the halos have King-model or isothermal profiles and the globular clusters formed with the same radial density profile as the underlying stellar population. We examine the summed radial distribution of the entire globular cluster systems and the bright globular cluster candidates in 51 Virgo and Fornax Cluster dEs for evidence of dynamical friction processes. We find that the summed distribution of the entire globular cluster population closely follows the exponential profile of the underlying stellar population. However, there is a deficit of bright clusters within the central regions of dEs (excluding the nuclei), perhaps due to the orbital decay of these massive clusters into the dE cores. We also predict the magnitude of each dE's nucleus assuming the nuclei form via dynamical friction. The observed trend of decreasing nuclear luminosity with decreasing dE luminosity is much stronger than predicted if the nuclei formed via simple dynamical friction processes. We find that the bright dE nuclei could have been formed from the merger of orbitally decayed massive clusters, but the faint nuclei are several magnitudes fainter than expected. These faint nuclei are found primarily in M_V > -14 dEs which have high globular cluster specific frequencies and extended globular cluster systems. In these galaxies, supernovae-driven winds, high central dark matter densities, extended dark matter halos, the formation of new star clusters, or tidal interactions may act to prevent dynamical friction from collapsing the entire globular cluster population into a single bright nucleus.Comment: 15 pages, 2 tables, 7 figures; to appear in the Astrophysical Journal, April 20, 200

C21orf57 is a human homologue of bacterial YbeY proteins

The product of the human C21orf57 (huYBEY) gene is predicted to be a homologue of the highly conserved YbeY proteins found in nearly all bacteria. We show that, like its bacterial and chloroplast counterparts, the HuYbeY protein is an RNase and that it retains sufficient function in common with bacterial YbeY proteins to partially suppress numerous aspects of the complex phenotype of an Escherichia coli ΔybeY mutant. Expression of HuYbeY in Saccharomyces cerevisiae, which lacks a YbeY homologue, results in a severe growth phenotype. This observation suggests that the function of HuYbeY in human cells is likely regulated through specific interactions with partner proteins similarly to the way YbeY is regulated in bacteria.National Institutes of Health (U.S.) (Grant GM31010)National Institutes of Health (U.S.) (Grant GM17151

Self-similar scaling and evolution in the galaxy cluster X-ray Luminosity-Temperature relation

We investigate the form and evolution of the X-ray luminosity-temperature (LT) relation of a sample of 114 galaxy clusters observed with Chandra at 0.1<z<1.3. The clusters were divided into subsamples based on their X-ray morphology or whether they host strong cool cores. We find that when the core regions are excluded, the most relaxed clusters (or those with the strongest cool cores) follow an LT relation with a slope that agrees well with simple self-similar expectations. This is supported by an analysis of the gas density profiles of the systems, which shows self-similar behaviour of the gas profiles of the relaxed clusters outside the core regions. By comparing our data with clusters in the REXCESS sample, which extends to lower masses, we find evidence that the self-similar behaviour of even the most relaxed clusters breaks at around 3.5keV. By contrast, the LT slopes of the subsamples of unrelaxed systems (or those without strong cool cores) are significantly steeper than the self-similar model, with lower mass systems appearing less luminous and higher mass systems appearing more luminous than the self-similar relation. We argue that these results are consistent with a model of non-gravitational energy input in clusters that combines central heating with entropy enhancements from merger shocks. Such enhancements could extend the impact of central energy input to larger radii in unrelaxed clusters, as suggested by our data. We also examine the evolution of the LT relation, and find that while the data appear inconsistent with simple self-similar evolution, the differences can be plausibly explained by selection bias, and thus we find no reason to rule out self-similar evolution. We show that the fraction of cool core clusters in our (non-representative) sample decreases at z>0.5 and discuss the effect of this on measurements of the evolution in the LT relation.Comment: 21 pages, 15 figures. Submitted to MNRAS. Comments welcom

The SAURON project. II. Sample and early results

Early results are reported from the SAURON survey of the kinematics and stellar populations of a representative sample of nearby E, S0 and Sa galaxies. The survey is aimed at determining the intrinsic shape of the galaxies, their orbital structure, the mass-to-light ratio as a function of radius, the age and metallicity of the stellar populations, and the frequency of kinematically decoupled cores and nuclear black holes. The construction of the representative sample is described, and its properties are illustrated. A comparison with long-slit spectroscopic data establishes that the SAURON measurements are comparable to, or better than, the highest-quality determinations. Comparisons are presented for NGC 3384 and NGC 4365 where stellar velocities and velocity dispersions are determined to a precision of 6 km/s, and the h3 and h4 parameters of the line-of-sight velocity distribution to a precision of better than 0.02. Extraction of accurate gas emission-line intensities, velocities and line widths from the datacubes is illustrated for NGC 5813. Comparisons with published line-strengths for NGC 3384 and NGC 5813 reveal uncertainties of < 0.1 A on the measurements of the Hbeta, Mgb and Fe5270 indices. Integral-field mapping uniquely connects measurements of the kinematics and stellar populations to the galaxy morphology. The maps presented here illustrate the rich stellar kinematics, gaseous kinematics, and line-strength distributions of early-type galaxies. The results include the discovery of a thin, edge-on, disk in NGC 3623, confirm the axisymmetric shape of the central region of M32, illustrate the LINER nucleus and surrounding counter-rotating star-forming ring in NGC 7742, and suggest a uniform stellar population in the decoupled core galaxy NGC 5813.Comment: 20 pages, 17 figures. To be published in MNRAS. Version with full resolution images available at http://www.strw.leidenuniv.nl/~dynamics/Instruments/Sauron/pub_list.htm

XMM-Newton study of the lensing cluster of galaxies CL0024+17

We present a detailed gravitational mass measurement based on the XMM-Newton imaging spectroscopy analysis of the lensing cluster of galaxies CL0024+17 at z=0.395. The emission appears approximately symmetric. However, on the scale of r~3.3' some indication of elongation is visible in the northwest-southeast (NW-SE) direction from the hardness ratio map (HRM). Within 3', we measure a global gas temperature of 3.52\pm0.17 keV, metallicity of 0.22\pm0.07, and bolometric luminosity of 2.9\pm0.1 \times 10^{44} h^{-2}_{70} erg/s. We derive a temperature distribution with an isothermal temperature of 3.9 keV to a radius of 1.5' and a temperature gradient in the outskirts (1.3<r<3'). Under the assumption of hydrostatic equilibrium, we measure gravitational mass and gas mass fraction to be M_{200}=2.0\pm0.3 \times 10^{14} h_{70}^{-1} M_{\odot} and f_{\rm gas}=0.20\pm0.03 h^{-3/2}_{70} at r_{200}=1.05 h^{-1}_{70} Mpc using the observed temperature profile. The complex structure in the core region is the key to explaining the discrepancy in gravitational mass determined from XMM-Newton X-ray observations and HST optical lensing measurements.Comment: 16 pages, 12 figures, to appear in A&

Galaxy mapping with the SAURON integral-field spectrograph: The star formation history of NGC 4365

We report the first wide-field mapping of the kinematics and stellar populations in the E3 galaxy NGC 4365. The velocity maps extend previous long-slit work. They show two independent kinematic subsystems: the central 300 x 700 pc rotates about the projected minor axis, and the main body of the galaxy, 3 x 4 kpc, rotates almost at right angles to this. The line-strength maps show that the metallicity of the stellar population decreases from a central value greater than solar, to one-half solar at a radius of 2 kpc. The decoupled core and main body of the galaxy have the same luminosity-weighted age, of ~14 Gyr, and the same elevated magnesium-to-iron ratio. The two kinematically distinct components have thus shared a common star formation history. We infer that the galaxy underwent a sequence of mergers associated with dissipative star formation that ended >12 Gyr ago. The misalignment between the photometric and kinematic axes of the main body is unambiguous evidence of triaxiality. The similarity of the stellar populations in the two components suggests that the observed kinematic structure has not changed substantially in 12 Gyr.Comment: 5 pages, accepted for publication in ApJ Letter

The DYMECS project: a statistical approach for the evaluation of convective storms in high-resolution NWP models

A new frontier in weather forecasting is emerging by operational forecast models now being run at convection-permitting resolutions at many national weather services. However, this is not a panacea; significant systematic errors remain in the character of convective storms and rainfall distributions. The DYMECS project (Dynamical and Microphysical Evolution of Convective Storms) is taking a fundamentally new approach to evaluate and improve such models: rather than relying on a limited number of cases, which may not be representative, we have gathered a large database of 3D storm structures on 40 convective days using the Chilbolton radar in southern England. We have related these structures to storm life-cycles derived by tracking features in the rainfall from the UK radar network, and compared them statistically to storm structures in the Met Office model, which we ran at horizontal grid length between 1.5 km and 100 m, including simulations with different subgrid mixing length. We also evaluated the scale and intensity of convective updrafts using a new radar technique. We find that the horizontal size of simulated convective storms and the updrafts within them is much too large at 1.5-km resolution, such that the convective mass flux of individual updrafts can be too large by an order of magnitude. The scale of precipitation cores and updrafts decreases steadily with decreasing grid lengths, as does the typical storm lifetime. The 200-m grid-length simulation with standard mixing length performs best over all diagnostics, although a greater mixing length improves the representation of deep convective storms

Exploring the impact of group identity at university on psychological and behavioural outcomes

With respect to supporting student well-being and success, the current research developed a peer support scheme, built on the principles of Social Identity Theory (SIT). This was targeted towards first year undergraduate psychology students, in which measures of collective identity, sense of belonging, group efficacy, happiness and resilience were obtained, along with attendance and academic attainment. Following one academic year of being part of our peer support scheme, participants (N= 90) completed a questionnaire and consented to their attendance and attainment data to be used. It was found that students’ collective identity was positively related to their sense of belonging, group efficacy beliefs and happiness. Further, the sense of belonging was a reliable predictor of happiness, but not attendance or academic attainment. Therefore, there is some evidence to suggest that a SIT-driven peer support scheme can support students’ psychosocial well-being, although more is needed to ascertain whether this could be developed further to observe any course-related outcomes. Theoretical contributions to SIT are therefore presented, in which the insights can be applied to Higher Education beyond the UK