An Infrared/X-ray Survey for New Members of the Taurus Star-Forming Region

We present the results of a search for new members of the Taurus star-forming region using data from the Spitzer Space Telescope and the XMM-Newton Observatory. We have obtained optical and near-infrared spectra of 44 sources that exhibit red Spitzer colors that are indicative of stars with circumstellar disks and 51 candidate young stars that were identified by Scelsi and coworkers using XMM-Newton. We also performed spectroscopy on four possible companions to members of Taurus that were reported by Kraus and Hillenbrand. Through these spectra, we have demonstrated the youth and membership of 41 sources, 10 of which were independently confirmed as young stars by Scelsi and coworkers. Five of the new Taurus members are likely to be brown dwarfs based on their late spectral types (>M6). One of the brown dwarfs has a spectral type of L0, making it the first known L-type member of Taurus and the least massive known member of the region (M=4-7 M_Jup). Another brown dwarf exhibits a flat infrared spectral energy distribution, which indicates that it could be in the protostellar class I stage (star+disk+envelope). Upon inspection of archival images from various observatories, we find that one of the new young stars has a large edge-on disk (r=2.5=350 AU). The scattered light from this disk has undergone significant variability on a time scale of days in optical images from the Canada-France-Hawaii Telescope. Using the updated census of Taurus, we have measured the initial mass function for the fields observed by XMM-Newton. The resulting mass function is similar to previous ones that we have reported for Taurus, showing a surplus of stars at spectral types of K7-M1 (0.6-0.8 M_sun) relative to other nearby star-forming regions like IC 348, Chamaeleon I, and the Orion Nebula Cluster

Fundamental Parameters of He-Weak and He-Strong Stars

We carried out low resolution spectroscopic observations in the wavelength range 3400-4700 A of 20 He-weak and 8 He-strong stars to determine their fundamental parameters by means of the Divan-Chalonge-Barbier (BCD) spectrophotometric system. For a few He-weak stars we also estimate the effective temperatures and the angular diameters by integrating absolute fluxes observed over a wide spectral range. Non-LTE model calculations are carried out to study the influence of the He/H abundance ratio on the emergent radiation of He-strong stars and on their Teff determination. We find that the effective temperatures, surface gravities and bolometric absolute magnitudes of He-weak stars estimated with the BCD system and the integrated flux method are in good agreement between each other, and they also agree with previous determinations based on several different methods. The mean discrepancy between the visual absolute magnitudes derived using the Hipparcos parallaxes and the BCD values is on average 0.3 mag for He-weak stars, while it is 0.5 mag for He-strong stars. For He-strong stars, we note that the BCD calibration, based on stars in the solar environment, leads to overestimated values of Teff. By means of model atmosphere calculations with enhanced He/H abundance ratios we show that larger He/H ratios produce smaller BD which naturally explains the Teff overestimation. We take advantage of these calculations to introduce a method to estimate the He/H abundance ratio in He-strong stars. The BD of HD 37479 suggests that the Teff of this star remains fairly constant as the star spectrum undergoes changes in the intensity of H and He absorption lines. Data for the He-strong star HD 66765 are reported for the first time.Comment: Accepted for publication in A&

Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression

Methionine adenosyltransferase α1 (MATα1, encoded by MAT1A) is responsible for hepatic biosynthesis of S‐adenosyl methionine, the principal methyl donor. MATα1 also act as a transcriptional cofactor by interacting and influencing the activity of several transcription factors. Mat1a knockout (KO) mice have increased levels of cytochrome P450 2E1 (CYP2E1), but the underlying mechanisms are unknown. The aims of the current study were to identify binding partners of MATα1 and elucidate how MATα1 regulates CYP2E1 expression. We identified binding partners of MATα1 by coimmunoprecipitation (co‐IP) and mass spectrometry. Interacting proteins were confirmed using co‐IP using recombinant proteins, liver lysates, and mitochondria. Alcoholic liver disease (ALD) samples were used to confirm relevance of our findings. We found that MATα1 negatively regulates CYP2E1 at mRNA and protein levels, with the latter being the dominant mechanism. MATα1 interacts with many proteins but with a predominance of mitochondrial proteins including CYP2E1. We found that MATα1 is present in the mitochondrial matrix of hepatocytes using immunogold electron microscopy. Mat1a KO hepatocytes had reduced mitochondrial membrane potential and higher mitochondrial reactive oxygen species, both of which were normalized when MAT1A was overexpressed. In addition, KO hepatocytes were sensitized to ethanol and tumor necrosis factor α–induced mitochondrial dysfunction. Interaction of MATα1 with CYP2E1 was direct, and this facilitated CYP2E1 methylation at R379, leading to its degradation through the proteasomal pathway. Mat1a KO livers have a reduced methylated/total CYP2E1 ratio. MATα1’s influence on mitochondrial function is largely mediated by its effect on CYP2E1 expression. Patients with ALD have reduced MATα1 levels and a decrease in methylated/total CYP2E1 ratio. Conclusion: Our findings highlight a critical role of MATα1 in regulating mitochondrial function by suppressing CYP2E1 expression at multiple levels

Search for Associations Containing Young stars (SACY): I. Sample & Searching Method

We report results from a high-resolution optical spectroscopic survey aimed to search for nearby young associations and young stars among optical counterparts of ROSAT All-Sky Survey X-ray sources in the Southern Hemisphere. We selected 1953 late-type (B-V >= 0.6), potentially young, optical counterparts out of a total of 9574 1RXS sources for follow-up observations. At least one high-resolution spectrum was obtained for each of 1511 targets. This paper is the first in a series presenting the results of the SACY survey. Here we describe our sample and our observations. We describe a convergence method in the (UVW) velocity space to find associations. As an example, we discuss the validity of this method in the framework of the BetaPic Association.Comment: Accepted for publication in A&

S4N: A Spectroscopic Survey of Stars in the Solar Neighborhood

[ABRIDGED] We report the results of a high-resolution spectroscopic survey of all the stars more luminous than Mv = 6.5 mag within 14.5 pc from the Sun. We derive stellar parameters and perform a preliminary abundance and kinematic analysis of the F-G-K stars in the sample. The inferred metallicity ([Fe/H]) distribution is centered at about -0.1 dex, and shows a standard deviation of 0.2 dex. We identify a number of metal-rich K-type stars which appear to be very old, confirming the claims for the existence of such stars in the solar neighborhood. With atmospheric effective temperatures and gravities derived independently of the spectra, we find that our classical LTE model-atmosphere analysis of metal-rich (and mainly K-type) stars provides discrepant abundances from neutral and ionized lines of several metals. Based on transitions of majority species, we discuss abundances of 16 chemical elements. In agreement with earlier studies we find that the abundance ratios to iron of Si, Sc, Ti, Co, and Zn become smaller as the iron abundance increases until approaching the solar values, but the trends reverse for higher iron abundances. At any given metallicity, stars with a `low' galactic rotational velocity tend to have high abundances of Mg, Si, Ca, Sc, Ti, Co, Zn, and Eu, but low abundances of Ba, Ce, and Nd. The Sun appears deficient by roughly 0.1 dex in O, Si, Ca, Sc, Ti, Y, Ce, Nd, and Eu, compared to its immediate neighbors with similar iron abundances.Comment: 24 pages, 19 figures, to appear in A&A; data can be accessed from http://hebe.as.utexas.edu/s4n/ or http://www.astro.uu.se/~s4n

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen

Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease (NAFLD) by increasing mitochondrial fatty acid oxidation

Nonalcoholic fatty liver disease (NAFLD) is considered the next major health epidemic with an estimated 25% worldwide prevalence. No drugs have yet been approved and NAFLD remains a major unmet need. Here, we identify MCJ (Methylation-Controlled J protein) as a target for non-alcoholic steatohepatitis (NASH), an advanced phase of NAFLD. MCJ is an endogenous negative regulator of the respiratory chain Complex I that acts to restrain mitochondrial respiration. We show that therapeutic targeting of MCJ in the liver with nanoparticle- and GalNAc-formulated siRNA efficiently reduces liver lipid accumulation and fibrosis in multiple NASH mouse models. Decreasing MCJ expression enhances the capacity of hepatocytes to mediate beta -oxidation of fatty acids and minimizes lipid accumulation, which results in reduced hepatocyte damage and fibrosis. Moreover, MCJ levels in the liver of NAFLD patients are elevated relative to healthy subjects. Thus, inhibition of MCJ emerges as an alternative approach to treat NAFLD. Non-alcoholic fatty liver (NAFLD) disease causes degeneration of the liver, affects about 25% of people globally, and has no approved treatment. Here, the authors show that the therapeutic siRNA-driven silencing of MCJ in the liver is an effective and safe treatment for NAFLD in multiple mouse models.We thank Douglas Taatjes and Nicole Bouffard for help with confocal microscopy analysis (Microscopy Imaging Center) at the University of Vermont. We also thank the University of Vermont Medical Center's Department of Pathology and Laboratory Medicine Histology and Clinical Laboratories for assistance with liver section staining and AST/ALT measurement, respectively. This work was supported by NIH STTR R41DK112429 (M.R.), NIH PO GM103496 (M.R.), Mitotherapeutix LLC (M.R., K.F, and M.L.M.-C.), MINECO/Feder SAF2015-65327-R and RTI2018-096494-B-100 (J.A.), MINECO/Feder SAF2017-87301-R (M.L.M-C.), BIOEF (M.L.M.-C.), EITB Maratoia BIO15/CA/014 (M.L.M-C), BBVA (M.L.M.-C.), La Caixa Foundation (M.L.M.-C.), Basque Country Health Department 2013111114 (M.L.M-C), MINECO/Feder SAF2015-64352-R (P.A.) and MINECO-Feder RTI2018-095134-B-100 (P.A.). ISCIII-Feder PI17/00535 (C.G.-M.), ISCIII-Feder CP14/00181, and PI16/00823 (A.G-R.), and Francisco Cobos Foundation (A.G.-R.). CIC bioGUNE is the recipient of a Severo Ochoa Excellence Accreditation (SEV-2016-0644) by the Ministry of Science, Innovation and Universities