Intercellular Friction and Motility Drive Orientational Order in Cell Monolayers

Spatiotemporal patterns in multicellular systems are important to understanding tissue dynamics, for instance, during embryonic development and disease. Here, we use a multiphase field model to study numerically the behavior of a near-confluent monolayer of deformable cells with intercellular friction. Varying friction and cell motility drives a solid-liquid transition, and near the transition boundary, we find the emergence of nematic order of cell deformation driven by shear-aligning cellular flows. Intercellular friction endows the monolayer with a finite viscosity, which significantly increases the spatial correlation in the flow and, concomitantly, the extent of nematic order. We also show that hexatic and nematic order are tightly coupled and propose a mechanical-geometric model for the colocalization of +1/2 nematic defects and 5-7 disclination pairs, which are the structural defects in the hexatic phase. Such topological defects coincide with regions of high cell-cell overlap, suggesting that they may mediate cellular extrusion from the monolayer, as found experimentally. Our results delineate a mechanical basis for the recent observation of nematic and hexatic order in multicellular collectives in experiments and simulations and pinpoint a generic pathway to couple topological and physical effects in these systems

Fake anti-malarials: start with the facts.

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting

Surgical management of primary colonic lymphoma: Big data for a rare problem

Background and ObjectivesPrimary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short‐term outcomes, and five‐year survival of patients undergoing nonpalliative surgery for PCL.MethodsWe performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis.ResultsWe identified 2153 patients. Median patient age was 68. Diffuse large B‐cell lymphoma accounted for 57% of tumors. 30‐ and 90‐Day mortality were high (5.6% and 11.1%, respectively). Thirty‐nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5‐year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07‐1.51; P = .01).ConclusionsPatients undergoing surgery for PCL have high rates of margin positivity and high short‐term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150597/1/jso25582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150597/2/jso25582.pd

RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription

Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting and proliferation in primary human blood versus lymphatic endothelial cells. We demonstrate that nuclear RhoB-GTP controls expression of distinct gene sets in each endothelial lineage by regulating VEZF1-mediated transcription. Finally, we identify a small-molecule inhibitor of VEZF1–DNA interaction that recapitulates RhoB loss in ischaemic retinopathy. Our findings establish the first intra-endothelial molecular pathway governing the phased response of angiogenesis and lymphangiogenesis following injury

No More Active Galactic Nuclei in Clumpy Disks Than in Smooth Galaxies at z~2 in CANDELS / 3D-HST

We use CANDELS imaging, 3D-HST spectroscopy, and Chandra X-ray data to investigate if active galactic nuclei (AGNs) are preferentially fueled by violent disk instabilities funneling gas into galaxy centers at 1.3<z<2.4. We select galaxies undergoing gravitational instabilities using the number of clumps and degree of patchiness as proxies. The CANDELS visual classification system is used to identify 44 clumpy disk galaxies, along with mass-matched comparison samples of smooth and intermediate morphology galaxies. We note that, despite being being mass-matched and having similar star formation rates, the smoother galaxies tend to be smaller disks with more prominent bulges compared to the clumpy galaxies. The lack of smooth extended disks is probably a general feature of the z~2 galaxy population, and means we cannot directly compare with the clumpy and smooth extended disks observed at lower redshift. We find that z~2 clumpy galaxies have slightly enhanced AGN fractions selected by integrated line ratios (in the mass-excitation method), but the spatially resolved line ratios indicate this is likely due to extended phenomena rather than nuclear AGNs. Meanwhile the X-ray data show that clumpy, smooth, and intermediate galaxies have nearly indistinguishable AGN fractions derived from both individual detections and stacked non-detections. The data demonstrate that AGN fueling modes at z~1.85 - whether violent disk instabilities or secular processes - are as efficient in smooth galaxies as they are in clumpy galaxies.Comment: ApJ accepted. 17 pages, 17 figure

Alignment of Brightest Cluster Galaxies with their Host Clusters

We examine the alignment between Brightest Cluster Galaxies (BCGs) and their host clusters in a sample of 7031 clusters with 0.08<z<0.44 found using a matched-filter algorithm and an independent sample of 5744 clusters with 0.1<z<0.3 selected with the maxBCG algorithm, both extracted from the Sloan Digital Sky Survey Data Release 6 imaging data. We confirm that BCGs are preferentially aligned with the cluster's major axis; clusters with dominant BCGs (>0.65 mag brighter than the mean of the second and third ranked galaxies) show stronger alignment than do clusters with less dominant BCGs at the 4.4 sigma level. Rich clusters show a stronger alignment than do poor clusters at the 2.3 sigma level. Low redshift clusters (z<0.26) show more alignment than do high redshift (z>0.26) clusters, with a difference significant at the 3.0 sigma level. Our results do not depend on the algorithm used to select the cluster sample, suggesting that they are not biased by systematics of either algorithm. The correlation between BCG dominance and cluster alignment may be a consequence of the hierarchical merging process which forms the cluster. The observed redshift evolution may follow from secondary infall at late redshifts.Comment: 15 pages, 12 Figures, 10 Tables, Accepted for publication in MNRA

Star formation at the edge of the Local Group: a rising star formation history in the isolated galaxy WLM

We present the star formation history (SFH) of the isolated (D~970 kpc) Local Group dwarf galaxy WLM measured from color-magnitude diagrams constructed from deep Hubble Space Telescope imaging. Our observations include a central (0.5 $r_h$) and outer field (0.7 $r_h$) that reach below the oldest main sequence turnoff. WLM has no early dominant episode of star formation: 20% of its stellar mass formed by ~12.5 Gyr ago (z~5). It also has an SFR that rises to the present with 50% of the stellar mass within the most recent 5 Gyr (z<0.7). There is evidence of a strong age gradient: the mean age of the outer field is 5 Gyr older than the inner field despite being only 0.4 kpc apart. Some models suggest such steep gradients are associated with strong stellar feedback and dark matter core creation. The SFHs of real isolated dwarf galaxies and those from the the Feedback In Realistic Environment suite are in good agreement for $M_{\star}(z=0) \sim 10^7-10^9 M_{\odot}$, but in worse agreement at lower masses ($M_{\star}(z=0) \sim 10^5-10^7 M_{\odot}$). These differences may be explainable by systematics in the models (e.g., reionization model) and/or observations (HST field placement). We suggest that a coordinated effort to get deep CMDs between HST/JWST (crowded central fields) and WFIRST (wide-area halo coverage) is the optimal path for measuring global SFHs of isolated dwarf galaxies.Comment: 13 pages, 13 Figures, 4 Tables. Re-submitted to MNRAS after addressing the referee's comment

The GALEX Arecibo SDSS Survey. I. Gas Fraction Scaling Relations of Massive Galaxies and First Data Release

We introduce the GALEX Arecibo SDSS Survey (GASS), an on-going large program that is gathering high quality HI-line spectra using the Arecibo radio telescope for an unbiased sample of ~1000 galaxies with stellar masses greater than 10^10 Msun and redshifts 0.025<z<0.05, selected from the SDSS spectroscopic and GALEX imaging surveys. The galaxies are observed until detected or until a low gas mass fraction limit (1.5-5%) is reached. This paper presents the first Data Release, consisting of ~20% of the final GASS sample. We use this data set to explore the main scaling relations of HI gas fraction with galaxy structure and NUV-r colour. A large fraction (~60%) of the galaxies in our sample are detected in HI. We find that the atomic gas fraction decreases strongly with stellar mass, stellar surface mass density and NUV-r colour, but is only weakly correlated with galaxy bulge-to-disk ratio (as measured by the concentration index of the r-band light). We also find that the fraction of galaxies with significant (more than a few percent) HI decreases sharply above a characteristic stellar surface mass density of 10^8.5 Msun kpc^-2. The fraction of gas-rich galaxies decreases much more smoothly with stellar mass. One of the key goals of GASS is to identify and quantify the incidence of galaxies that are transitioning between the blue, star-forming cloud and the red sequence of passively-evolving galaxies. Likely transition candidates can be identified as outliers from the mean scaling relations between gas fraction and other galaxy properties. [abridged]Comment: 25 pages, 12 figures. Accepted for publication in MNRAS. Version with high resolution figures available at http://www.mpa-garching.mpg.de/GASS/pubs.ph

The GALEX Arecibo SDSS Survey II: The Star Formation Efficiency of Massive Galaxies

We use measurements of the HI content, stellar mass and star formation rates in ~190 massive galaxies with stellar masses greater than 10^10 Msun, obtained from the Galex Arecibo SDSS Survey (GASS) described in Paper I (Catinella et al. 2010) to explore the global scaling relations associated with the bin-averaged ratio of the star formation rate over the HI mass, which we call the HI-based star formation efficiency (SFE). Unlike the mean specific star formation rate, which decreases with stellar mass and stellar mass surface density, the star formation efficiency remains relatively constant across the sample with a value close to SFE = 10^-9.5 yr^-1 (or an equivalent gas consumption timescale of ~3 Gyr). Specifically, we find little variation in SFE with stellar mass, stellar mass surface density, NUV-r color and concentration. We interpret these results as an indication that external processes or feedback mechanisms that control the gas supply are important for regulating star formation in massive galaxies. An investigation into the detailed distribution of SFEs reveals that approximately 5% of the sample shows high efficiencies with SFE > 10^-9 yr^-1, and we suggest that this is very likely due to a deficiency of cold gas rather than an excess star formation rate. Conversely, we also find a similar fraction of galaxies that appear to be gas-rich for their given specific star-formation rate, although these galaxies show both a higher than average gas fraction and lower than average specific star formation rate. Both of these populations are plausible candidates for "transition" galaxies, showing potential for a change (either decrease or increase) in their specific star formation rate in the near future. We also find that 36+/-5% of the total HI mass density and 47+/-5% of the total SFR density is found in galaxies with stellar mass greater than 10^10 Msun. [abridged]Comment: 18 pages, 11 figures. Accepted for publication in MNRAS. GASS publications and released data can be found at http://www.mpa-garching.mpg.de/GASS/index.ph

Ubiquitous outflows in DEEP2 spectra of star-forming galaxies at z=1.4

Galactic winds are a prime suspect for the metal enrichment of the intergalactic medium and may have a strong influence on the chemical evolution of galaxies and the nature of QSO absorption line systems. We use a sample of 1406 galaxy spectra at z~1.4 from the DEEP2 redshift survey to show that blueshifted Mg II 2796, 2803 A absorption is ubiquitous in starforming galaxies at this epoch. This is the first detection of frequent outflowing galactic winds at z~1. The presence and depth of absorption are independent of AGN spectral signatures or galaxy morphology; major mergers are not a prerequisite for driving a galactic wind from massive galaxies. Outflows are found in coadded spectra of galaxies spanning a range of 30x in stellar mass and 10x in star formation rate (SFR), calibrated from K-band and from MIPS IR fluxes. The outflows have column densities of order N_H ~ 10^20 cm^-2 and characteristic velocities of ~ 300-500 km/sec, with absorption seen out to 1000 km/sec in the most massive, highest SFR galaxies. The velocities suggest that the outflowing gas can escape into the IGM and that massive galaxies can produce cosmologically and chemically significant outflows. Both the Mg II equivalent width and the outflow velocity are larger for galaxies of higher stellar mass and SFR, with V_wind ~ SFR^0.3, similar to the scaling in low redshift IR-luminous galaxies. The high frequency of outflows in the star-forming galaxy population at z~1 indicates that galactic winds occur in the progenitors of massive spirals as well as those of ellipticals. The increase of outflow velocity with mass and SFR constrains theoretical models of galaxy evolution that include feedback from galactic winds, and may favor momentum-driven models for the wind physics.Comment: Accepted by ApJ. 25 pages, 17 figures. Revised to add discussions of intervening absorbers and AGN-driven outflows; conclusions unchange