MicroRNA-26a Is Strongly Downregulated in Melanoma and Induces Cell Death through Repression of Silencer of Death Domains (SODD)

Melanoma is an aggressive cancer that metastasizes rapidly and is refractory to conventional chemotherapies. Identifying microRNAs (miRNAs) that are responsible for this pathogenesis is therefore a promising means of developing new therapies. We identified miR-26a through microarray and quantitative reverse-transcription–PCR (qRT-PCR) experiments as an miRNA that is strongly downregulated in melanoma cell lines as compared with primary melanocytes. Treatment of cell lines with miR-26a mimic caused significant and rapid cell death compared with a negative control in most melanoma cell lines tested. In surveying targets of miR-26a, we found that protein levels of SMAD1 (mothers against decapentaplegic homolog 1) and BAG-4/SODD were strongly decreased in sensitive cells treated with miR-26a mimic as compared with the control. The luciferase reporter assays further demonstrated that miR-26a can repress gene expression through the binding site in the 3′ untranslated region (3′UTR) of SODD (silencer of death domains). Knockdown of these proteins with small interfering RNA (siRNA) showed that SODD has an important role in protecting melanoma cells from apoptosis in most cell lines sensitive to miR-26a, whereas SMAD1 may have a minor role. Furthermore, transfecting cells with a miR-26a inhibitor increased SODD expression. Our findings indicate that miR-26a replacement is a potential therapeutic strategy for metastatic melanoma, and that SODD, in particular, is a potentially useful therapeutic target

Spitzer observations of extended Lyman-alpha Clouds in the SSA22 field

We present the results of a Spitzer IRAC and MIPS 24 micron study of extended Lyman-alpha clouds (or Lyman-alpha Blobs, LABs) within the SSA22 filamentary structure at z = 3.09. We detect 6/26 LABs in all IRAC filters, four of which are also detected at 24 micron, and find good correspondence with the 850 micron measurements of Geach et al. 2005. An analysis of the rest-frame ultraviolet, optical, near- and mid-infrared colors reveals that these six systems exhibit signs of nuclear activity (AGN)and/or extreme star formation. Notably, they have properties that bridge galaxies dominated by star formation (Lyman-break galaxies; LBGs) and those with AGNs (LBGs classified as QSOs). The LAB systems not detected in all four IRAC bands, on the other hand, are, as a group, consistent with pure star forming systems, similar to the majority of the LBGs within the filament. These results indicate that the galaxies within LABs do not comprise a homogeneous population, though they are also consistent with scenarios in which the gas halos are ionized through a common mechanism such as galaxy-scale winds driven by the galaxies within them, or gravitational heating of the collapsing cloud itself.Comment: 11 pages, 6 figures, accepted for publication in the Astrophysical Journa

Health related quality of life six months following surgical treatment for secondary peritonitis – using the EQ-5D questionnaire

Background: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL. Design: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy. Setting: Multicenter study in two academic and seven regional teaching hospitals. Patients: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires. Results: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p <0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS. Conclusion: Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 month

HST/ACS Emission Line Imaging of Low Redshift 3CR Radio Galaxies I: The Data

We present 19 nearby (z<0.3) 3CR radio galaxies imaged at low- and high-excitation as part of a Cycle 15 Hubble Space Telescope snapshot survey with the Advanced Camera for Surveys. These images consist of exposures of the H-alpha (6563 \AA, plus [NII] contamination) and [OIII] 5007 \AA emission lines using narrow-band linear ramp filters adjusted according to the redshift of the target. To facilitate continuum subtraction, a single-pointing 60 s line-free exposure was taken with a medium-band filter appropriate for the target's redshift. We discuss the steps taken to reduce these images independently of the automated recalibration pipeline so as to use more recent ACS flat-field data as well as to better reject cosmic rays. We describe the method used to produce continuum-free (pure line-emission) images, and present these images along with qualitative descriptions of the narrow-line region morphologies we observe. We present H-alpha+[NII] and [OIII] line fluxes from aperture photometry, finding the values to fall expectedly on the redshift-luminosity trend from a past HST/WFPC2 emission line study of a larger, generally higher redshift subset of the 3CR. We also find expected trends between emission line luminosity and total radio power, as well as a positive correlation between the size of the emission line region and redshift. We discuss the associated interpretation of these results, and conclude with a summary of future work enabled by this dataset.Comment: 18 pages, 12 figures, accepted for publication in ApJ

Gas Accretion and Giant Lyman-alpha Nebulae

Several decades of observations and discoveries have shown that high-redshift AGN and massive galaxies are often surrounded by giant Lyman-alpha nebulae extending in some cases up to 500 kpc in size. In this review, I discuss the properties of the such nebulae discovered at z>2 and their connection with gas flows in and around the galaxies and their halos. In particular, I show how current observations are used to constrain the physical properties and origin of the emitting gas in terms of the Lyman-alpha photon production processes and kinematical signatures. These studies suggest that recombination radiation is the most viable scenario to explain the observed Lyman-alpha luminosities and Surface Brightness for the large majority of the nebulae and imply that a significant amount of dense, ionized and cold clumps should be present within and around the halos of massive galaxies. Spectroscopic studies suggest that, among the giant Lyman-alpha nebulae, the one associated with radio-loud AGN should have kinematics dominated by strong, ionized outflows within at least the inner 30-50 kpc. Radio-quiet nebulae instead present more quiescent kinematics compatible with stationary situation and, in some cases, suggestive of rotating structures. However, definitive evidences for accretion onto galaxies of the gas associated with the giant Lyman-alpha emission are not unambiguously detected yet. Deep surveys currently ongoing using other bright, non-resonant lines such as Hydrogen H-alpha and HeII1640 will be crucial to search for clearer signatures of cosmological gas accretion onto galaxies and AGN.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dave', to be published by Springe

Do Physicians with Self-Reported Non-English Fluency Practice in Linguistically Disadvantaged Communities?

BackgroundLanguage concordance between physicians and patients may reduce barriers to care faced by patients with limited English proficiency (LEP). It is unclear whether physicians with fluency in non-English languages practice in areas with high concentrations of people with LEP.ObjectiveTo investigate whether physician non-English language fluency is associated with practicing in areas with high concentrations of people with LEP.DesignCross-sectional cohort study.ParticipantsA total of 61,138 practicing physicians no longer in training who participated in the California Medical Board Physician Licensure Survey from 2001-2007.MeasuresSelf-reported language fluency in Spanish and Asian languages. Physician practice ZIP code corresponding to: (1) high concentration of people with LEP and (2) high concentration of linguistically isolated households.MethodsPractice location ZIP code was geocoded with geographic medical service study designations. We examined the unadjusted relationships between physician self-reported fluency in Spanish and selected Asian languages and practice location, stratified by race-ethnicity. We used staged logistic multiple variable regression models to isolate the effect of self-reported language fluency on practice location controlling for age, gender, race-ethnicity, medical specialty, and international medical graduate status.ResultsPhysicians with self-reported fluency in Spanish or an Asian language were more likely to practice in linguistically designated areas in these respective languages compared to those without fluency. Physician fluency in an Asian language [adjusted odds ratio (AOR) = 1.77; 95% confidence intervals (CI): 1.63-1.92] was independently associated with practicing in areas with a high number of LEP Asian speakers. A similar pattern was found for Spanish language fluency (AOR = 1.77; 95% CI: 1.43-1.82) and areas with high numbers of LEP Spanish-speakers. Latino and Asian race-ethnicity had the strongest effect on corresponding practice location, and this association was attenuated by language fluency.ConclusionsPhysicians who are fluent in Spanish or an Asian language are more likely to practice in geographic areas where their potential patients speak the corresponding language

Modelling the Pan-Spectral Energy Distribution of Starburst Galaxies: I. The role of ISM pressure & the Molecular Cloud Dissipation Timescale

In this paper, we combine the stellar spectral synthesis code STARBURST 99, the nebular modelling code MAPPINGS IIIq, a 1-D dynamical evolution model of \HII regions around massive clusters of young stars and a simplified model of synchrotron emissivity to produce purely theoretical self-consistent synthetic spectral energy distributions (SEDs) for (solar metallicity) starbursts lasting some $10^8$ years. These SEDs extend from the Lyman Limit to beyond 21 cm. We find that two ISM parameters control the form of the SED; the pressure in the diffuse phase of the ISM (or, equivalently, its density), and the molecular cloud dissipation timescale. We present detailed SED fits to Arp 220 and NGC 6240, and we give the predicted colors for starburst galaxies derived from our models for the IRAS and the Spitzer Space Observatory MIPS and IRAC instruments. Our models reproduce the spread in observed colors of starburst galaxies. Finally, we present absolute calibrations to convert observed fluxes into star formation rates in the UV (GALEX), at optical wavelengths (H$\alpha$), and in the IR (IRAS or the Spitzer Space Observatory). (Abstract Truncated)Comment: 56 pages, 16 figures, accepted by The Apstrophysical Journal For version with full, colour figures go to http://www.mso.anu.edu.au/~bgroves/starburst

Black hole accretion and host galaxies of obscured quasars in XMM-COSMOS

We explore the connection between black hole growth at the center of obscured quasars selected from the XMM-COSMOS survey and the physical properties of their host galaxies. We study a bolometric regime ( 8 x 10^45 erg/s) where several theoretical models invoke major galaxy mergers as the main fueling channel for black hole accretion. We confirm that obscured quasars mainly reside in massive galaxies (Mstar>10^10 Msun) and that the fraction of galaxies hosting such powerful quasars monotonically increases with the stellar mass. We stress the limitation of the use of rest-frame color-magnitude diagrams as a diagnostic tool for studying galaxy evolution and inferring the influence that AGN activity can have on such a process. We instead use the correlation between star-formation rate and stellar mass found for star-forming galaxies to discuss the physical properties of the hosts. We find that at z ~1, ~62% of Type-2 QSOs hosts are actively forming stars and that their rates are comparable to those measured for normal star-forming galaxies. The fraction of star-forming hosts increases with redshift: ~71% at z ~2, and 100% at z ~3. We also find that the the evolution from z ~1 to z ~3 of the specific star-formation rate of the Type-2 QSO hosts is in excellent agreement with that measured for star-forming galaxies. From the morphological analysis, we conclude that most of the objects are bulge-dominated galaxies, and that only a few of them exhibit signs of recent mergers or disks. Finally, bulge-dominated galaxies tend to host Type-2 QSOs with low Eddington ratios (lambda<0.1), while disk-dominated or merging galaxies have at their centers BHs accreting at high Eddington ratios (lambda > 0.1).Comment: Accepted by A&A. 20 pages, 16 figures, 2 tables. A version with higher resolution figures and SED fits of Appendix A is available at http://www.eso.org/~vmainier/QSO2/qso2.pd

Periodontal disease in a patient with Prader-Willi syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare.</p> <p>Case presentation</p> <p>We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution.</p> <p>Conclusions</p> <p>Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.</p

Magnetic support of the optical emission line filaments in NGC 1275

The giant elliptical galaxy NGC 1275, at the centre of the Perseus cluster, is surrounded by a well-known giant nebulosity of emission-line filaments, which are plausibly about >10^8 yr old. The filaments are dragged out from the centre of the galaxy by the radio bubbles rising buoyantly in the hot intracluster gas before later falling back. They act as dramatic markers of the feedback process by which energy is transferred from the central massive black hole to the surrounding gas. The mechanism by which the filaments are stabilized against tidal shear and dissipation into the surrounding 4x10^7 K gas has been unclear. Here we report new observations that resolve thread-like structures in the filaments. Some threads extend over 6 kpc, yet are only 70 pc wide. We conclude that magnetic fields in the threads, in pressure balance with the surrounding gas, stabilize the filaments, so allowing a large mass of cold gas to accumulate and delay star formation.Comment: Published in Nature, includes supplementary information, high resolution images available at http://www-xray.ast.cam.ac.uk/papers/ngc1275