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

Average Metallicity and Star Formation Rate of Lya Emitters Probed by a Triple Narrow-Band Survey

We present the average metallicity and star-formation rate of Lya emitters (LAEs) measured from our large-area survey with three narrow-band (NB) filters covering the Lya, [OII]3727, and Ha+[NII] lines of LAEs at z=2.2. We select 919 z=2.2 LAEs from Subaru/Suprime-Cam NB data in conjunction with Magellan/IMACS spectroscopy. Of these LAEs, 561 and 105 are observed with KPNO/NEWFIRM near-infrared NB filters whose central wavelengths are matched to redshifted [OII] and Ha nebular lines, respectively. By stacking the near-infrared images of the LAEs, we successfully obtain average nebular-line fluxes of LAEs, the majority of which are too faint to be identified individually by narrow-band imaging or deep spectroscopy. The stacked object has an Ha luminosity of 1.7x10^{42} erg s^{-1} corresponding to a star formation rate (SFR) of 14 M_{sun} yr^{-1}. We place, for the first time, a firm lower limit to the average metallicity of LAEs of Z>~0.09 Z_{sun} (2sigma) based on the [OII]/(Ha+[NII]) index together with photo-ionization models and empirical relations. This lower limit of metallicity rules out the hypothesis that LAEs, so far observed at z~2, are extremely metal poor (Z<2x10^{-2} Z_{sun}) young galaxies at the 4sigma level. This limit is higher than a simple extrapolation of the observed mass-metallicity relation of z~2 UV-selected galaxies toward lower masses (5x10^{8} M_{sun}), but roughly consistent with a recently proposed fundamental mass-metallicity relation when the LAEs' relatively low SFR is taken into account. The Ha and Lya luminosities of our NB-selected LAEs indicate that the escape fraction of Lya photons is ~12-30 %, much higher than the values derived for other galaxy populations at z~2.Comment: 21 pages, 15 figures, 8 tables. Accepted for publication in Ap

First Spectroscopic Evidence for High Ionization State and Low Oxygen Abundance in Lya Emitters

We present results from Keck/NIRSPEC and Magellan/MMIRS follow-up spectroscopy of Lya emitters (LAEs) at z=2.2 identified in our Subaru narrowband survey. We successfully detect Ha emission from seven LAEs, and perform a detailed analysis of six LAEs free from AGN activity, two out of which, CDFS-3865 and COSMOS-30679, have [OII] and [OIII] line detections. They are the first [OII]-detected LAEs at high-z, and their [OIII]/[OII] ratios and R23-indices provide the first simultaneous determinations of ionization parameter and oxygen abundance for LAEs. CDFS-3865 has a very high ionization parameter (q_{ion}=2.5^{+1.7}_{-0.8}x10^8 cm s^{-1}) and a low oxygen abundance (12+log(O/H)=7.84^{+0.24}_{-0.25}) in contrast with moderate values of other high-z galaxies such as Lyman-break galaxies (LBGs). COSMOS-30679 also possesses a relatively high ionization parameter (q_{ion}=8^{+10}_{-4}x10^7 cm s^{-1}) and a low oxygen abundance (12+log(O/H)=8.18^{+0.28}_{-0.28}). Both LAEs appear to fall below the mass-metallicity relation of z~2 LBGs. Similarly, a low metallicity of 12+log(O/H)<8.4 is independently indicated for typical LAEs from a composite spectrum and the [NII]/Ha index. Such high ionization parameters and low oxygen abundances can be found in local star-forming galaxies, but this extreme local population occupies only ~0.06% of the SDSS spectroscopic galaxy sample with a number density ~100 times smaller than that of LAEs. With their high ionization parameters and low oxygen abundances, LAEs would represent an early stage of galaxy formation dominated by massive stars in compact star-forming regions. High-q_{ion} galaxies like LAEs would produce ionizing photons efficiently with a high escape fraction achieved by density-bounded HII regions, which would significantly contribute to cosmic reionization at z>6.Comment: 19 pages, 11 figures. Accepted for publication in Ap

A feasibility randomised controlled trial with an embedded qualitative evaluation of perinatal emotional skills groups for women with borderline personality disorder : protocol for the EASE study

Background Borderline personality disorder (BPD) is a severe mental disorder characterised by emotional instability, impaired interpersonal functioning and an increased risk of suicide. There is no clear evidence about how best to help women with BPD during the perinatal period. Perinatal Emotional Skills Groups (ESGs) consist of 12 group sessions, focussing on core skills in emotion regulation, interpersonal effectiveness, distress tolerance and mindfulness and how these skills can best be utilised during the perinatal period. Prior observational research has shown that perinatal ESGs may help women with BPD. We set out to test the feasibility of conducting a randomised controlled trial to investigate the clinical effectiveness of perinatal ESGs. Methods A two-arm, parallel-group, feasibility randomised controlled trial of Perinatal ESGs in addition to Treatment as Usual (TAU) versus TAU for women aged over 18 years, who are likely to have a diagnosis of BPD and are either pregnant or are within 12 months of having a live birth. We will exclude women who have a co-existing organic, psychotic mental disorder or substance use dependence syndrome; those with cognitive or language difficulties that would preclude them from consenting or participating in study procedures; those judged to pose an acute risk to their baby and those requiring admission to a mother and baby unit. After consenting to participation and completing screening assessments, eligible individuals will be randomly allocated, on a 1:1 ratio, to either ESGs + TAU or to TAU. Randomisation will be stratified according to recruitment centre. Feasibility outcomes will be the proportion of participants: (1) consenting; (2) completing baseline measures and randomised; (3) completing the intervention and (4) completing follow-up assessments. All study participants will complete a battery of self-report measures at 2 and 4 months post-randomisation. A nested qualitative study will examine participants’ and therapists’ experiences of the trial and the intervention. Discussion Evidence is lacking about how to help women with BPD during the perinatal period. Perinatal ESGs are a promising intervention and if they prove to be an effective adjunct to usual care, a large population of vulnerable women and their children could experience substantial health gains. Trial registration ISRCTN80470632

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

On-the-job and off-the-job embeddedness differentially influence relationships between informal job search and turnover

Whereas informal job search (i.e., using personal contacts for job search) is positively associated with the receipt of job offers, research has yet to consider the extent to which informal job search translates into current employees\u27 turnover decisions or to investigate factors that may restrain (or facilitate) the translation of informal job search into turnover decisions. In this study, we propose that on-the-job and off-the-job embeddedness play distinct roles in strengthening or weakening the positive relationship between informal job search and turnover intentions and behavior. We assert that on-the-job embeddedness reduces the likelihood that informal job search translates into turnover decisions, whereas off-the-job embeddedness strengthens the positive association between informal job search and turnover decisions. We tested these hypotheses across two samples of employed nurses. Although results were mixed, we found evidence that on-the-job embeddedness dampened the positive relationships of informal job search with turnover intentions and behaviors, whereas off-the-job embeddedness facilitated the positive relationships between informal job search and turnover decisions. Taken together, findings suggest that on-the-job and off-the-job embeddedness influence informal job search processes differently. We discuss the implications of these findings for how organizations manage employees\u27 informal job search activities as well as how researchers approach the study of job embeddedness