We present the first APOKASC catalog of spectroscopic and asteroseismic properties of 1916 red giants observed in the Kepler fields. The spectroscopic parameters provided from the Apache Point ...Observatory Galactic Evolution Experiment project are complemented with asteroseismic surface gravities, masses, radii, and mean densities determined by members of the Kepler Asteroseismology Science Consortium. We assess both random and systematic sources of error and include a discussion of sample selection for giants in the Kepler fields. Total uncertainties in the main catalog properties are of the order of 80 K in T sub(eff), 0.06 dex in M/H, 0.014 dex in log g, and 12% and 5% in mass and radius, respectively; these reflect a combination of systematic and random errors. Asteroseismic surface gravities are substantially more precise and accurate than spectroscopic ones, and we find good agreement between their mean values and the calibrated spectroscopic surface gravities. There are, however, systematic underlying trends with T sub(eff) and log g. Our effective temperature scale is between 0 and 200 K cooler than that expected from the infrared flux method, depending on the adopted extinction map, which provides evidence for a lower value on average than that inferred for the Kepler Input Catalog (KIC). We find a reasonable correspondence between the photometric KIC and spectroscopic APOKASC metallicity scales, with increased dispersion in KIC metallicities as the absolute metal abundance decreases, and offsets in T sub(eff) and log g consistent with those derived in the literature. We present mean fitting relations between APOKASC and KIC observables and discuss future prospects, strengths, and limitations of the catalog data.
We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated ...the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 × 10−10 and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.
Abstract
Prompted by peculiar spectroscopic variability observed in SDSS/APOGEE
H
-band spectra, we monitored the Be star HD 55606 using optical spectroscopy and found that it is an exotic ...double-lined spectroscopic binary (SB2) consisting of a Be star and a hot, compact companion that is probably an OB subdwarf (sdOB) star. The motion of the sdOB star is traced by its impact on the strong He
i
lines, observed as radial velocity (
V
r
) variable, double-peaked emission profiles with narrow central absorption cores. Weak He
ii
4686 Å absorption associated with the companion star is detected in most spectra. Use of the emission peaks of low-ionization emission lines to trace the Be star
V
r
and the He
i
lines to trace the companion star
V
r
yields a circular orbital solution with a 93.8 day period and masses of
M
Be
= 6.2
M
⊙
and
M
sdOB
= 0.9
M
⊙
in the case of
i
= 80°. HD 55606 exhibits a variety of phase-locked variability, including the development of shell lines twice per orbit. The shell phases coincide with variation in the double emission peak separations, and both forms of variability are likely caused by a two-armed spiral density perturbation in the Be disk. The intensity ratios of the double emission peaks are also phase-locked, possibly indicating heating by the sdOB star of the side of the Be disk facing it. HD 55606 is a new member of the growing sample of Be+sdOB binaries, in which the Be star’s rapid rotation and ability to form a disk can be attributed to past mass-transfer.
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone‐H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify ...non‐histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin‐independent role of Ezh2 during T‐cell development and immune homeostasis. T‐cell‐specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2‐deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2‐deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin‐independent function of Ezh2 that impacts on the development of the immune system.
Synopsis
Increasing evidence indicates that the histone methyltransferase Ezh2 also modifies non‐histone substrates in a chromatin‐independent fashion. This study shows that Ezh2 controls immune homeostasis through such a non‐canonical mechanism by directly methylating the transcription factor PLZF.
Loss of Ezh2 leads to the accumulation of PLZFhigh NKT cells, whereas the depletion of Eed and Suz12 blocks NKT cell development.
PLZF in the expanded Ezh2‐depleted NKT cell population shows increased protein stability.
Ezh2‐dependent methylation of PLZF creates a “methyl degron”, which promotes the ubiquitinylation and degradation of PLZF.
Ezh2‐deficient PLZFhigh NKT cells perturb the homeostasis of T cells and B cells.
Increasing evidence indicates that the histone methyltransferase Ezh2 also modifies non‐histone substrates in a chromatin‐independent fashion. This study shows that Ezh2 controls immune homeostasis through such a non‐canonical mechanism by directly methylating the transcription factor PLZF.
Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30 % of HGGs). To identify additional driver mutations in ...HGGs, we investigated a cohort of 60 pediatric HGGs using whole-exome sequencing (WES) and compared them to 543 exomes from non-cancer control samples. We identified mutations in
SETD2
, a H3K36 trimethyltransferase, in 15 % of pediatric HGGs, a result that was genome-wide significant (FDR = 0.029). Most
SETD2
alterations were truncating mutations. Sequencing the gene in this cohort and another validation cohort (123 gliomas from all ages and grades) showed
SETD2
mutations to be specific to high-grade tumors affecting 15 % of pediatric HGGs (11/73) and 8 % of adult HGGs (5/65) while no
SETD2
mutations were identified in low-grade diffuse gliomas (0/45). Furthermore,
SETD2
mutations were mutually exclusive with
H3F3A
mutations in HGGs (
P
= 0.0492) while they partly overlapped with
IDH1
mutations (4/14), and
SETD2
-mutant tumors were found exclusively in the cerebral hemispheres (
P
= 0.0055). SETD2 is the only H3K36 trimethyltransferase in humans, and
SETD2
-mutant tumors showed a substantial decrease in H3K36me3 levels (
P
< 0.001), indicating that the mutations are loss-of-function. These data suggest that loss-of-function SETD2 mutations occur in older children and young adults and are specific to HGG of the cerebral cortex, similar to the H3.3 G34R/V and IDH mutations. Taken together, our results suggest that mutations disrupting the histone code at H3K36, including H3.3 G34R/V, IDH1 and/or SETD2 mutations, are central to the genesis of hemispheric HGGs in older children and young adults.
Abstract
We report the discovery of a new ultra-faint stellar system found near the Magellanic Clouds in the DECam Local Volume Exploration Survey. This new system, DELVE J0155−6815 (DELVE 2), is ...located at a heliocentric distance of
D
⊙
= 71 ± 4 kpc, which places it at a 3D physical separation of 12 ± 3 kpc from the center of the Small Magellanic Cloud and
from the center of the Large Magellanic Cloud (LMC). DELVE 2 is identified as a resolved overdensity of old (
τ
> 13.3 Gyr) and metal-poor (
dex) stars with a projected half-light radius of
and an absolute magnitude of
. The size and luminosity of DELVE 2 are consistent with both the population of recently discovered ultra-faint globular clusters and the smallest ultra-faint dwarf galaxies. However, its photometrically derived age and metallicity would place it among the oldest and most metal-poor globular clusters in the Magellanic system. In the absence of spectroscopic measurements of the system’s metallicity dispersion and internal kinematics, we are unable to conclusively classify this system at this time. DELVE 2 is detected in
Gaia
DR2 with a clear proper-motion signal, with multiple blue horizontal-branch stars near the centroid of the system with proper motions consistent with the systemic mean. We measure the system proper motion to be
=
mas yr
−1
. We compare the spatial position and proper motion of DELVE 2 with simulations of the accreted satellite population of the LMC and find that it is very likely to be associated with the LMC.
Whole exome sequencing (WES) has greatly facilitated the identification of causal mutations for diverse human genetic disorders. We applied WES as a molecular diagnostic tool to identify ...disease‐causing genes in consanguineous families in Qatar. Seventeen consanguineous families with diverse disorders were recruited. Initial mutation screening of known genes related to the clinical diagnoses did not reveal the causative mutations. Using WES approach, we identified the definitive disease‐causing mutations in four families: (i) a novel nonsense homozygous (c.1034C>G) in PHKG2 causing glycogen storage disease type 9C (GSD9C) in a male with initial diagnosis of GSD3; (ii) a novel homozygous 1‐bp deletion (c.915del) in NSUN2 in a male proband with Noonan‐like syndrome; (iii) a homozygous SNV (c.1598C>G) in exon 11 of IDUA causing Hurler syndrome in a female proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation (c.1645+1G>A) in PHEX in a female proband with initial diagnosis of autosomal recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the unambiguous identification of disease‐causing mutations in phenotypically complex disorders or correction of the initial clinical diagnosis in ˜25% of our cases.
The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several
human cancers, including basal cell carcinoma, medulloblastoma, and ...sarcomas. We identified 147 genes whose levels of expression
were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras -expressing cells established a set of genes unique to GLI1 -induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras -expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus
DNA-binding sequences were identified in the 5â² regions of cyclin D2, IGFBP-6 , osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed
the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were
demonstrated in GLI1 -amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1 -induced cell transformation occurs through multiple downstream pathways.
ABSTRACT The SDSS-III/Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey operated from 2011-2014 using the APOGEE spectrograph, which collects high-resolution (R ∼ 22,500), ...near-IR (1.51-1.70 m) spectra with a multiplexing (300 fiber-fed objects) capability. We describe the survey data products that are publicly available, which include catalogs with radial velocity, stellar parameters, and 15 elemental abundances for over 150,000 stars, as well as the more than 500,000 spectra from which these quantities are derived. Calibration relations for the stellar parameters ( , , M/H, /M) and abundances (C, N, O, Na, Mg, Al, Si, S, K, Ca, Ti, V, Mn, Fe, Ni) are presented and discussed. The internal scatter of the abundances within clusters indicates that abundance precision is generally between 0.05 and 0.09 dex across a broad temperature range; it is smaller for some elemental abundances within more limited ranges and at high signal-to-noise ratio. We assess the accuracy of the abundances using comparison of mean cluster metallicities with literature values, APOGEE observations of the solar spectrum and of Arcturus, comparison of individual star abundances with other measurements, and consideration of the locus of derived parameters and abundances of the entire sample, and find that it is challenging to determine the absolute abundance scale; external accuracy may be good to 0.1-0.2 dex. Uncertainties may be larger at cooler temperatures ( ). Access to the public data release and data products is described, and some guidance for using the data products is provided.
ABSTRACT We present the discovery of a new dwarf galaxy, Hydra II, found serendipitously within the data from the ongoing Survey of the Magellanic Stellar History conducted with the Dark Energy ...Camera on the Blanco 4 m Telescope. The new satellite is compact ( 11 pc) and faint ( 0.3), but well within the realm of dwarf galaxies. The stellar distribution of Hydra II in the color-magnitude diagram is well-described by a metal-poor ( ) and old (13 Gyr) isochrone and shows a distinct blue horizontal branch, some possible red clump stars, and faint stars that are suggestive of blue stragglers. At a heliocentric distance of 134 10 kpc, Hydra II is located in a region of the Galactic halo that models have suggested may host material from the leading arm of the Magellanic Stream. A comparison with N-body simulations hints that the new dwarf galaxy could be or could have been a satellite of the Magellanic Clouds.
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