The N2K Consortium. VII. Atmospheric Parameters of 1907 Metal-Rich Stars: Finding Planet-Search Targets

We report high-precision atmospheric parameters for 1907 stars in the N2K low-resolution spectroscopic survey, designed to identify metal-rich FGK dwarfs likely to harbor detectable planets. 284 of these stars are in the ideal temperature range for planet searches, T_eff <= 6000K, and have a 10% or greater probability of hosting planets based on their metallicities. The stars in the low-resolution spectroscopic survey should eventually yield >60 new planets, including 8-9 hot Jupiters. Short-period planets have already been discovered orbiting the survey targets HIP 14801 and HD 149143.Comment: Accepted for publication in Astrophysical Journal Supplements. 24 pages, including 8 figures and one table. Two more tables will appear in ApJS online editio

Mutations in the Gene DNAJC5 Cause Autosomal Dominant Kufs Disease in a Proportion of Cases: Study of the Parry Family and 8 Other Families

Background: The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD). Methodology and Principal Findings We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p.Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment. Conclusions: Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change

Conservation of the endemic dwarf carnivores of Cozumel Island, Mexico.

Cozumel Island, Mexico, harbours two endemic species of dwarf procyonids: the Pygmy Raccoon Procyon pygmaeus and the Dwarf Coati Nasua nelsoni. Both species are Critically Endangered, and are among the world&rsquo;s most threatened Carnivora. Here we summarise the research we have been conducting on their ecology, evolution, genetics, and conservation. We also summarise the conservation initiatives we have been undertaking and promoting in order to advance the conservation of these unique species and their habitats. This effort illustrates the importance of an interdisciplinary approach in conservation science and action in maximising effectiveness. Nevertheless, the precarious status of the species make it imperative to continue and expand the work we have carried out in Cozumel to prevent two imminent global extinctions.<br /

Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis

Genome-wide association studies (GWAS) conducted using commercial single nucleotide polymorphisms (SNP) arrays have proven to be a powerful tool for the detection of common disease susceptibility variants. However, their utility for the detection of lower frequency variants is yet to be practically investigated. Here we describe the application of a rare variant collapsing method to a large genome-wide SNP dataset, the Wellcome Trust Case Control Consortium rheumatoid arthritis (RA) GWAS. We partitioned the data into gene-centric bins and collapsed genotypes of low frequency variants (defined here as MAF ≤0.05) into a single count coupled with univariate analysis. We then prioritised gene regions for further investigation in an independent cohort of 3,355 cases and 2,427 controls based on rare variant signal p value and prior evidence to support involvement in RA. A total of 14,536 gene bins were investigated in the primary analysis and signals mapping to the TNFAIP3 and chr17q24 loci were selected for further investigation. We detected replicating association to low frequency variants in the TNFAIP3 gene (combined p = 6.6 × 10−6). Even though rare variants are not well-represented and can be difficult to genotype in GWAS, our study supports the application of low frequency variant collapsing methods to genome-wide SNP datasets as a means of exploiting data that are routinely ignored

Microevolution of Pandemic Vibrio parahaemolyticus Assessed by the Number of Repeat Units in Short Sequence Tandem Repeat Regions

The emergence of the pandemic strain Vibrio parahaemolyticus O3:K6 in 1996 caused a large increase of diarrhea outbreaks related to seafood consumption in Southeast Asia, and later worldwide. Isolates of this strain constitutes a clonal complex, and their effectual differentiation is possible by comparison of their variable number tandem repeats (VNTRs). The differentiation of the isolates by the differences in VNTRs will allow inferring the population dynamics and microevolution of this strain but this requires knowing the rate and mechanism of VNTRs' variation. Our study of mutants obtained after serial cultivation of clones showed that mutation rates of the six VNTRs examined are on the order of 10−4 mutant per generation and that difference increases by stepwise addition of single mutations. The single stepwise mutation (SSM) was deduced because mutants with 1, 2, 3, or more repeat unit deletions or insertions follow a geometric distribution. Plausible phylogenetic trees are obtained when, according to SSM, the genetic distance between clusters with different number of repeats is assessed by the absolute differences in repeats. Using this approach, mutants originated from different isolates of pandemic V. parahaemolyticus after serial cultivation are clustered with their parental isolates. Additionally, isolates of pandemic V. parahaemolyticus from Southeast Asia, Tokyo, and northern and southern Chile are clustered according their geographical origin. The deepest split in these four populations is observed between the Tokyo and southern Chile populations. We conclude that proper phylogenetic relations and successful tracing of pandemic V. parahaemolyticus requires measuring the differences between isolates by the absolute number of repeats in the VNTRs considered

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Early Science with the Large Millimeter Telescope: Detection of Dust Emission in Multiple Images of a Normal Galaxy at z \u3e 4 Lensed by a Frontier Fields Cluster

We directly detect dust emission in an optically detected, multiply imaged galaxy lensed by the Frontier Fields cluster MACSJ0717.5+3745. We detect two images of the same galaxy at 1.1 mm with the AzTEC camera on the Large Millimeter Telescope leaving no ambiguity in the counterpart identification. This galaxy, MACS0717_Az9, is at z \u3e 4 and the strong lensing model (μ=7.5) allows us to calculate an intrinsic IR luminosity of 9.7 × 1010 Le and an obscured star formation rate of 14.6 ± 4.5 Me yr−1. The unobscured star formation rate from the UV is only 4.1 ± 0.3 Me yr−1, which means the total star formation rate (18.7 ± 4.5 Me yr−1) is dominated (75%–80%) by the obscured component. With an intrinsic stellar mass of only 6.9 × 109 Me, MACS0717_Az9 is one of only a handful of z \u3e 4 galaxies at these lower masses that is detected in dust emission. This galaxy lies close to the estimated star formation sequence at this epoch. However, it does not lie on the dust obscuration relation (IRX-β) for local starburst galaxies and is instead consistent with the Small Magellanic Cloud attenuation law. This remarkable lower mass galaxy, showing signs of both low metallicity and high dust content, may challenge our picture of dust production in the early universe

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN