On the MBM12 Young Association

I present a comprehensive study of the MBM12 young association (MBM12A). By combining infrared (IR) photometry from the Two-Micron All-Sky Survey (2MASS) survey with new optical imaging and spectroscopy, I have performed a census of the MBM12A membership that is complete to 0.03 Msun (H~15) for a 1.75deg X 1.4deg field encompassing the MBM12 cloud. I find five new members with masses of 0.1-0.4 Msun and a few additional candidates that have not been observed spectroscopically. From an analysis of optical and IR photometry for stars in the direction of MBM12, I identify M dwarfs in the foreground and background of the cloud. By comparing the magnitudes of these stars to those of local field dwarfs, I arrive at a distance modulus 7.2+/-0.5 (275 pc) to the MBM12 cloud; it is not the nearest molecular cloud and is not inside the local bubble of hot ionized gas as had been implied by previous distance estimates of 50-100 pc. I have also used Li strengths and H-R diagrams to constrain the absolute and relative ages of MBM12A and other young populations; these data indicate ages of 2 +3/-1 Myr for MBM12A and 10 Myr for the TW Hya and Eta Cha associations. MBM12A may be a slightly evolved version of the aggregates of young stars within the Taurus dark clouds (~1 Myr) near the age of the IC 348 cluster (~2 Myr).Comment: to be published in The Astrophysical Journal, 41 pages, 14 figures, also found at http://cfa-www.harvard.edu/sfgroup/preprints.htm

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. a-Aminonitriles—prebiotic a–amino acid precursors—are generally produced by Strecker reactions. However, cysteine’s aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable—but energy-rich—a-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis

Large scale grain mantle disruption in the Galactic Center

We present observations of C2H5OH toward molecular clouds in Sgr A, Sgr B2 and associated with thermal and non-thermal features in the Galactic center. C2H5OH emission in Sgr A and Sgr B2 is widespread, but not uniform. C2H5OH emission is much weaker or it is not detected in some molecular clouds in both complexes, in particular those with radial velocities between 70 and 120 km/s. While most of the clouds associated with the thermal features do not show C2H5OH emission, that associated with the Non-Thermal Radio Arc shows emission. The fractional abundance of C2H5OH in most of the clouds with radial velocities between 0 and 70 km/s in Sgr A and Sgr B2 is relatively high, of few 1e-8. The C2H5OH abundance decreases by more than one order of magnitude (aprox. 1e-9) in the clouds associated with the thermal features. The large abundance of C2H5OH in the gas-phase indicates that C2H5OH has formed in grains and released to gas-phase by shocks in the last aprox. 1e5 years.Comment: In press in Astrophysical Journal Letters 7 pages, 1 table, 1 figur

The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors

The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease.FC-A, LG-G, JCL, AS, PG-M, SEL-P, SM and JA are supported by Asociación Pablo Ugarte and Miguelañez SA, ASION-La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027). TGPG is supported by a grant from ‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)’, the Daimler and Benz Foundation in cooperation with the Reinhard Frank Foundation, by LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder—Bettina-Bräu-Stiftung’, the Walter Schulz Foundation, the Fritz Thyssen Foundation (FTH-40.15.0.030MN) and by the German Cancer Aid (DKH-111886 and DKH-70112257). The ‘Genetics and Biology of Cancers’ team (TGPG, DS and OD) is supported by grants from the Ligue Nationale Contre Le Cancer (Equipe labellisée). This work was also supported by the European PROVABES, ASSET and EEC FP7 grants. We also thank the following associations for their invaluable support: the Société Française des Cancers de l’Enfant, Courir pour Mathieu, Dans les pas du Géant, Olivier Chape, Les Bagouzamanon, Enfants et Santé and les Amis de Claire. We thank Dr S Navarro (University of Valencia, Valencia, Spain) and Dr TJ Triche (Children’s Hospital Los Angeles, Los Angeles, USA) for providing us with Ewing sarcoma cell lines A4573 and TTC-466, respectively.S

INCLUDING INDIGENOUS AND LOCAL KNOWLEDGE IN THE WORK OF THE INTERGOVERNMENTAL SCIENCE-POLICY PLATFORM ON BIODIVERSITY AND ECOSYSTEM SERVICES (IPBES) GLOBAL ASSESSMENT : Outcomes and lessons for the future

This chapter makes a strong case for greater inclusion of Indigenous and Local Knowledge (ILK) in global environmental policy fora and in science-policy interfaces. The chapter specifically looks at the IPBES Global Assessment which has developed one of the first global-scale mechanisms for operationalizing ILK in sustainability decision-making. The types of knowledges that have been successfully integrated into this assessment include ways in which ILK can help (1) to assess ecosystem change and associated human vulnerability; (2) to inform the achievement of global goals like the Sustainable Development Goals and Aichi Targets; and (3) to inform policy-relevant options for decision-makers. It is argued that other global initiatives seeking to engage ILK in their endeavours can learn from the ILK approach of the IPBES Global Assessment.Peer reviewe

X-Ray Flares and Oscillations from the Black Hole Candidate X-Ray Transient XTE J1650-500 at Low Luminosity

We report on X-ray observations made with the Rossi X-ray Timing Explorer of the black hole candidate (BHC) transient XTE J1650-500 at the end of its first, and currently only, outburst. By monitoring the source at low luminosities over several months, we found 6 bright ~100 second X-ray flares and long time scale oscillations of the X-ray flux. The oscillations are aperiodic with a characteristic time scale of 14.2 days and an order of magnitude variation in the 2.8-20 keV flux. The oscillations may be related to optical "mini-outbursts" that have been observed at the ends of outbursts for other short orbital period BHC transients. The X-ray flares have durations between 62 and 215 seconds and peak fluxes that are 5-24 times higher than the persistent flux. The flares have non-thermal energy spectra and occur when the persistent luminosity is near 3E34 (d/4 kpc)^2 erg/s (2.8-20 keV). The rise time for the brightest flare demonstrates that physical models for BHC systems must be able to account for the situation where the X-ray flux increases by a factor of up to 24 on a time scale of seconds. We discuss the flares in the context of observations and theory of Galactic BHCs and compare the flares to those detected from Sgr A*, the super-massive black hole at the Galactic center. We also compare the flares to X-ray bursts that are seen in neutron star systems. While some of the flare light curves are similar to those of neutron star bursts, the flares have non-thermal energy spectra in contrast to the blackbody spectra exhibited in bursts. This indicates that X-ray bursts should not be taken as evidence that a given system contains a neutron star unless the presence of a blackbody component in the burst spectrum can be demonstrated.Comment: 9 pages, accepted by Ap