X-ray flares in Orion young stars. I. Flare characteristics

Pre-main sequence (PMS) stars are known to produce powerful X-ray flares which resemble magnetic reconnection solar flares scaled by factors up to 10^4. However, numerous puzzles are present including the structure of X-ray emitting coronae and magnetospheres, effects of protoplanetary disks, and effects of stellar rotation. To investigate these issues in detail, we examine 216 of the brightest flares from 161 PMS stars observed in the Chandra Orion Ultradeep Project (COUP). These constitute the largest homogeneous dataset of PMS, or indeed stellar flares at any stellar age, ever acquired. Our effort is based on a new flare spectral analysis technique that avoids nonlinear parametric modeling. It can be applied to much weaker flares and is more sensitive than standard methods. We provide a catalog with >30 derived flare properties and an electronic atlas for this unique collection of stellar X-ray flares. The current study (Paper I) examines the flare morphologies, and provides general comparison of COUP flare characteristics with those of other active X-ray stars and the Sun. Paper II will concentrate on relationships between flare behavior, protoplanetary disks, and other stellar properties. Several results are obtained. First, the COUP flares studied here are among the most powerful, longest, and hottest stellar X-ray flares ever studied. Second, no significant statistical differences in peak flare luminosity or temperature distributions are found among different morphological flare classes, suggesting a common underlying mechanism for all flares. Third, comparison with the general solar-scaling laws indicates that COUP flares may not fit adequately proposed power-temperature and duration-temperature solar-stellar fits. Fourth, COUP super-hot flares are found to be brighter but shorter than ... ABRIDGEDComment: Accepted for publication in ApJ (07/11/08); 63 pages, 16 figures, 4 table

X-Ray flares in Orion Young Stars. II. Flares, Magnetospheres, and Protoplanetary Disks

We study the properties of powerful X-ray flares from 161 pre-main sequence (PMS) stars observed with the Chandra X-ray Observatory in the Orion Nebula region. Relationships between flare properties, protoplanetary disks and accretion are examined in detail to test models of star-disk interactions at the inner edge of the accretion disks. Previous studies had found no differences in flaring between diskfree and accreting systems other than a small overall diminution of X-ray luminosity in accreting systems. The most important finding is that X-ray coronal extents in fast-rotating diskfree stars can significantly exceed the Keplerian corotation radius, whereas X-ray loop sizes in disky and accreting systems do not exceed the corotation radius. This is consistent with models of star-disk magnetic interaction where the inner disk truncates and confines the PMS stellar magnetosphere. We also find two differences between flares in accreting and diskfree PMS stars. First, a subclass of super-hot flares with peak plasma temperatures exceeding 100 MK are preferentially present in accreting systems. Second, we tentatively find that accreting stars produce flares with shorter durations. Both results may be consequences of the distortion and destabilization of the stellar magnetosphere by the interacting disk. Finally, we find no evidence that any flare types, even slow-rise flat-top flares are produced in star-disk magnetic loops. All are consistent with enhanced solar long-duration events with both footprints anchored in the stellar surface.Comment: Accepted for publication in ApJ (07/17/08); 46 pages, 14 figures, 2 table

X-ray Study of Triggered Star Formation and Protostars in IC 1396N

The IC 1396N cometary globule within the large nearby HII region IC 1396 has been observed with the ACIS detector on board the Chandra X-ray Observatory. We detect 117 X-ray sources, of which ~50-60 are likely members of the young open cluster Trumpler~37 dispersed throughout the HII region, and 25 are associated with young stars formed within the globule. Spitzer/2MASS photometry shows the X-ray population is very young: 3 older Class III stars, 16 classical T Tauri stars, 6 protostars including a Class 0/I system. We infer a total T Tauri population of ~30 stars in the globule, including the undetected population, with a star formation efficiency of 1-4%. An elongated source spatial distribution with an age gradient oriented towards the exciting star is discovered in the X-ray population of IC 1396N, supporting similar findings in other cometary globules. The geometric and age distribution is consistent with the RDI model for triggered star formation in CGs by HII region shocks. The inferred velocity of the shock front propagating into the globule is ~0.6km/s. The large number of X-ray-luminous protostars in the globule suggests either an unusually high ratio of Class I/0 vs. Class II/III stars, or a non-standard IMF favoring higher mass stars by the triggering process. The Chandra source associated with the luminous Class 0/I protostar IRAS 21391+5802 is one of the youngest stars ever detected in the X-ray band. We also establish for the first time that the X-ray absorption in protostars arises from the local infalling envelopes rather than ambient molecular cloud material.Comment: 50 pages, 11 figures, 6 tables, accepted for publication in ApJ 09/11/0

p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis

Genome organizer Satb1 is regulated by p63 and contributes to epidermal morphogenesis by remodeling chromatin structure and gene expression at the epidermal differentiation complex locus

The Multi-Level Action of Fatty Acids on Adiponectin Production by Fat Cells

Current epidemics of diabetes mellitus is largely caused by wide spread obesity. The best-established connection between obesity and insulin resistance is the elevated and/or dysregulated levels of circulating free fatty acids that cause and aggravate insulin resistance, type 2 diabetes, cardiovascular disease and other hazardous metabolic conditions. Here, we investigated the effect of a major dietary saturated fatty acid, palmitate, on the insulin-sensitizing adipokine adiponectin produced by cultured adipocytes. We have found that palmitate rapidly inhibits transcription of the adiponectin gene and the release of adiponectin from adipocytes. Adiponectin gene expression is controlled primarily by PPARγ and C/EBPα. Using mouse embryonic fibroblasts from C/EBPα-null mice, we have determined that the latter transcription factor may not solely mediate the inhibitory effect of palmitate on adiponectin transcription leaving PPARγ as a likely target of palmitate. In agreement with this model, palmitate increases phosphorylation of PPARγ on Ser273, and substitution of PPARγ for the unphosphorylated mutant Ser273Ala blocks the effect of palmitate on adiponectin transcription. The inhibitory effect of palmitate on adiponectin gene expression requires its intracellular metabolism via the acyl-CoA synthetase 1-mediated pathway. In addition, we found that palmitate stimulates degradation of intracellular adiponectin by lysosomes, and the lysosomal inhibitor, chloroquine, suppressed the effect of palmitate on adiponectin release from adipocytes. We present evidence suggesting that the intracellular sorting receptor, sortilin, plays an important role in targeting of adiponectin to lysosomes. Thus, palmitate not only decreases adiponectin expression at the level of transcription but may also stimulate lysosomal degradation of newly synthesized adiponectin

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

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