Characterization of star-forming dwarf galaxies at 0.1 ≲ z ≲ 0.9 in VUDS: Probing the low-mass end of the mass-metallicity relation

We present the discovery and spectrophotometric characterization of a large sample of 164 faint ($i_{AB}$ $\sim$ $23$-$25$ mag) star-forming dwarf galaxies (SFDGs) at redshift $0.13$ $\leq z \leq$ $0.88$ selected by the presence of bright optical emission lines in the VIMOS Ultra Deep Survey (VUDS). We investigate their integrated physical properties and ionization conditions, which are used to discuss the low-mass end of the mass-metallicity relation (MZR) and other key scaling relations. We use optical VUDS spectra in the COSMOS, VVDS-02h, and ECDF-S fields, as well as deep multiwavelength photometry, to derive stellar masses, star formation rates (SFR) and gas-phase metallicities. The VUDS SFDGs are compact (median $r_{e}$ $\sim$ $1.2$ kpc), low-mass ($M_{*}$ $\sim$ $10^7-10^9$ $M_{\odot}$) galaxies with a wide range of star formation rates (SFR($H\alpha$) $\sim 10^{-3}-10^{1}$ $M_{\odot}/yr$) and morphologies. Overall, they show a broad range of subsolar metallicities (12+log(O/H)=$7.26$-$8.7$; $0.04$ $\lesssim Z/Z_{\odot} \lesssim$ $1$). The MZR of SFDGs shows a flatter slope compared to previous studies of galaxies in the same mass range and redshift. We find the scatter of the MZR partly explained in the low mass range by varying specific SFRs and gas fractions amongst the galaxies in our sample. Compared with simple chemical evolution models we find that most SFDGs do not follow the predictions of a "closed-box" model, but those from a gas regulating model in which gas flows are considered. While strong stellar feedback may produce large-scale outflows favoring the cessation of vigorous star formation and promoting the removal of metals, younger and more metal-poor dwarfs may have recently accreted large amounts of fresh, very metal-poor gas, that is used to fuel current star formation

Phosphatase of Regenerating Liver-3 Localizes to Cyto-Membrane and Is Required for B16F1 Melanoma Cell Metastasis In Vitro and In Vivo

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) is a member of the novel phosphatases of regenerating liver family, characterized by one protein tyrosine phosphatase active domain and a C-terminal prenylation (CCVM) motif. Though widely proposed to facilitate metastasis in many cancer types, PRL-3's cellular localization and the function of its CCVM motif in metastatic process remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a series of Myc tagged PRL-3 wild type or mutant plasmids were expressed in B16F1 melanoma cells to investigate the relationship between PRL-3's cellular localization and metastasis. With immuno-fluorescence microcopy and cell adhesion/migration assay in vitro, and an experimental passive metastasis model in vivo, we found that CCVM motif is critical for the localization of PRL-3 on cell plasma membrane and the lung metastasis of melanoma. In particular, Cystine170 is the key site for prenylation in this process. CONCLUSIONS/SIGNIFICANCE: These results suggest that cellular localization of PRL-3 is highly correlated with its function in tumor metastasis, and inhibition of PRL-3 prenylation might be a new approach to cancer therapy

The ALPINE-ALMA [C ii] Survey: Size of Individual Star-forming Galaxies at z = 4-6 and Their Extended Halo Structure

We present the physical extent of [CII] 158um line-emitting gas from 46 star-forming galaxies at z=4-6 from the ALMA Large Program to INvestigate CII at Early Times (ALPINE). Using exponential profile fits, we measure the effective radius of the [CII] line (r_e,[CII]) for individual galaxies and compare them with the rest-frame ultra-violet (UV) continuum (r_e,UV) from Hubble Space Telescope images. The effective radius r_e,[CII] exceeds r_e,UV by factors of ~2-3 and the ratio of r_e,[CII]/r_e,UV increases as a function of M_star. We do not find strong evidence that [CII] line, the rest-frame UV, and FIR continuum are always displaced over ~ 1-kpc scale from each other. We identify 30% of isolated ALPINE sources as having an extended [CII] component over 10-kpc scales detected at 4.1$\sigma$-10.9$\sigma$ beyond the size of rest-frame UV and far-infrared (FIR) continuum. One object has tentative rotating features up to ~10-kpc, where the 3D model fit shows the rotating [CII]-gas disk spread over 4 times larger than the rest-frame UV-emitting region. Galaxies with the extended [CII] line structure have high star-formation rate (SFR), stellar mass (M_star), low Lya equivalent-width, and more blue-shifted (red-shifted) rest-frame UV metal absorption (Lya line), as compared to galaxies without such extended [CII] structures. Although we cannot rule out the possibility that a selection bias towards luminous objects may be responsible for such trends, the star-formation driven outflow also explains all these trends. Deeper observations are essential to test whether the extended [CII] line structures are ubiquitous to high-z star-forming galaxies.ERC STF

The ALPINE-ALMA [CII] survey: Dust attenuation properties and obscured star formation at z ∼4.4-5.8

We present dust attenuation properties of spectroscopically confirmed star forming galaxies on the main sequence at redshift ~4.4-5.8. Our analyses are based on the far infrared continuum observations of 118 galaxies at rest-frame $158\,\rm{\mu m}$ obtained with the ALMA large program ALPINE. We study the connection between the UV spectral slope ($\beta$), stellar mass ($M_{\star}$), and infrared excess (IRX$=L_{\rm{IR}}/L_{\rm{UV}}$). Twenty-three galaxies are individually detected in the continuum at $>3.5\,\sigma$ significance. We perform a stacking analysis using both detections and non-detections to study the average dust attenuation properties at z~4.4-5.8. The individual detections and stacks show that the IRX-$\beta$ relation at z~5 is consistent with a steeper dust attenuation curve than typically found at lower redshifts (z<4). The attenuation curve is similar to or even steeper than that of the extinction curve of the Small Magellanic Cloud (SMC). This systematic change of the IRX-$\beta$ relation as a function of redshift suggests an evolution of dust attenuation properties at $z>4$. Similarly, we find that our galaxies have lower IRX values up to 1 dex on average at fixed mass compared to previously studied IRX-$M_{\star}$ relations at $z\lesssim4$, albeit with significant scatter. This implies a lower obscured fraction of star-formation than at lower redshifts. Our results suggest that dust properties of UV-selected star forming galaxies at $z\gtrsim4$ are characterised by (i) a steeper attenuation curve than at $z\lesssim4$, and (ii) a rapidly decreasing dust obscured fraction of star formation as a function of redshift. Nevertheless, even among this UV-selected sample, massive galaxies ($\log M_{\star}/M_\odot > 10$) at z~5-6 already exhibit an obscured fraction of star formation of $\sim45\%$, indicating a rapid build-up of dust during the epoch of reionization.STFC ER

A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.Spanish Ministry of Science and Innovation (grant BIO2008-04212)Spanish Ministry of Science and Innovation (grant FIS PI 08/0440)GVA-FEDER (PROMETEO/2010/001)Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grant RD06/0020/1019)Instituto de Salud Carlos III (ISCIII)Spanish Ministry of Science and InnovationSpanish Ministry of Health (FI06/00027

Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth

Hepatocyte growth factor (HGF) and its receptor Met are responsible for a wide variety of cellular responses, both physiologically during embryo development and tissue homeostasis, and pathologically, particularly during tumor growth and dissemination. In cancer, Met can act as an oncogene on tumor cells, as well as a pro-angiogenic factor activating endothelial cells and inducing new vessel formation. Molecules interfering with Met activity could be valuable therapeutic agents. Here we have investigated the antiangiogenic properties of a synthetic peptide mimicking the docking site of the Met carboxyl-terminal tail, which was delivered into the cells by fusion with the internalization sequences from Antennapedia or HIV-Tat. We showed that these peptides inhibit ligand-dependent endothelial cell proliferation, motility, invasiveness and morphogenesis in vitro to an even greater extent and with much less toxicity than the Met inhibitor PHA-665752, which correlated with interference of HGF-dependent downstream signaling. In vivo, the peptides inhibited HGF-induced angiogenesis in the matrigel sponge assay and impaired xenograft tumor growth and vascularization in Kaposi's sarcoma. These data show that interference with the Met receptor intracellular sequence impairs HGF-induced angiogenesis, suggesting the use of antidocking site compounds as a therapeutic strategy to counteract angiogenesis in cancer as well as in other diseases

New constraints on the average escape fraction of Lyman continuum radiation in z ∼ 4 galaxies from the VIMOS Ultra Deep Survey (VUDS)

Determining the average fraction of Lyman continuum (LyC) photons escaping high redshift galaxies is essential for understanding how reionization proceeded in the z>6 Universe. We want to measure the LyC signal from a sample of sources in the Chandra Deep Field South (CDFS) and COSMOS fields for which ultra-deep VIMOS spectroscopy as well as multi-wavelength Hubble Space Telescope (HST) imaging are available. We select a sample of 46 galaxies at $z\sim 4$ from the VIMOS Ultra Deep Survey (VUDS) database, such that the VUDS spectra contain the LyC part of the spectra, that is, the rest-frame range $880-910\AA$. Taking advantage of the HST imaging, we apply a careful cleaning procedure and reject all the sources showing nearby clumps with different colours, that could potentially be lower-redshift interlopers. After this procedure, the sample is reduced to 33 galaxies. We measure the ratio between ionizing flux (LyC at $895\AA$) and non-ionizing emission (at $\sim 1500 \AA$) for all individual sources. We also produce a normalized stacked spectrum of all sources. Assuming an intrinsic average $L_{\nu}(1470)/L_{\nu}(895)$ of 3, we estimate the individual and average relative escape fraction. We do not detect ionizing radiation from any individual source, although we identify a possible LyC emitter with very high Ly$\alpha$ equivalent width (EW). From the stacked spectrum and assuming a mean transmissivity for the sample, we measure a relative escape fraction $f_{esc}^{rel}=0.09\pm0.04$. We also look for correlations between the limits in the LyC flux and source properties and find a tentative correlation between LyC flux and the EW of the Ly$\alpha$ emission line. Our results imply that the LyC flux emitted by $V=25-26$ star-forming galaxies at z$\sim$4 is at most very modest, in agreement with previous upper limits from studies based on broad and narrow band imaging.This work is supported by funding from the European Research Council Advanced Grant ERC–2010–AdG–268107–EARLY and by INAF Grants PRIN 2010, PRIN 2012 and PICS 2013. AC, OC, MT and VS acknowledge the grant MIUR PRIN 2010– 2011. This work is based on data products made available at the CESAM data center, Laboratoire d’Astrophysique de Marseille. R.A. acknowledges support from the ERC Advanced Grant 695671 'QUENCH'

Hepatocyte Growth Factor (HGF) Inhibits Collagen I and IV Synthesis in Hepatic Stellate Cells by miRNA-29 Induction

BACKGROUND: In chronic liver disease, hepatic stellate cells (HSC) transdifferentiate into myofibroblasts, promoting extracellular matrix (ECM) synthesis and deposition. Stimulation of HSC by transforming growth factor-β (TGF-β) is a crucial event in liver fibrogenesis due to its impact on myofibroblastic transition and ECM induction. In contrast, hepatocyte growth factor (HGF), exerts antifibrotic activities. Recently, miR-29 has been reported to be involved in ECM synthesis. We therefore studied the influence of HGF and TGF-β on the miR-29 collagen axis in HSC. METHODOLOGY: HSC, isolated from rats, were characterized for HGF and Met receptor expression by Real-Time PCR and Western blotting during culture induced myofibroblastic transition. Then, the levels of TGF-β, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-β stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. The interaction of miR-29 with 3'-untranslated mRNA regions (UTR) was analyzed by reporter assays. The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29-mimicks by Real-Time PCR and immunoblotting. PRINCIPAL FINDINGS: The 3'-UTR of the collagen-1 and -4 subtypes were identified to bind miR-29. Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-β stimulation of HSC, in vitro. Finally, we show that during myofibroblastic transition and TGF-β exposure the HGF-receptor, Met, is upregulated in HSC. Thus, whereas TGF-β stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis. CONCLUSIONS: Upregulation of miRNA-29 by HGF and downregulation by TGF-β take part in the anti- or profibrogenic response of HSC, respectively