543 research outputs found

    Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

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    Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals

    New transitions and feeding of the J\u3csup\u3eπ\u3c/sup\u3e=(8\u3csup\u3e+\u3c/sup\u3e) isomer in \u3csup\u3e186\u3c/sup\u3eRe

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    The spallation neutron source at the Los Alamos Neutron Science Center Weapons Neutron Research facility was used to populate excited states in 186Re via (n,2nγ) reactions on an enriched 187Re target. Gamma rays were detected with the GErmanium Array for Neutron Induced Excitations spectrometer, a Compton-suppressed array of 18 HPGe detectors. Incident neutron energies were determined by the time-of-flight technique and used to obtain γ-ray excitation functions for the purpose of identifying γ rays by reaction channel. Analysis of the singles γ-ray spectrum gated on the neutron energy range 10≤En≤25MeV resulted in five transitions and one level added to the 186Re level scheme. The additions include the placement of three γ rays at 266.7, 381.2, and 647.7 keV which have been identified as feeding the 2.0×105yr, Jπ=(8+) isomer and yield an improved value of 148.2(5)keV for the isomer energy. These transitions may have astrophysical implications related to the use of the Re-Os cosmochronometer. Abstract © APS

    The echo-transponder electrode catheter: A new method for mapping the left ventricle

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    AbstractThe ability to locate catheter position in the left ventricle with respect to endocardial landmarks might enhance the accuracy of ventricular tachycardia mapping. An echotransponder system (Telectronics, Inc.) was compared with biplane fluoroscopy for left ventricular endocardial mapping. A 6F electrode catheter was modified with the addition of a piezoelectric crystal 5 mm from the tip. This crystal was connected to a transponder that received and transmitted ultrasound, resulting in a discrete artifact on the two-dimensional echocardiographic image corresponding to the position of the catheter tip.Catheters were introduced percutaneously into the left ventricle of nine anesthetized dogs. Two-dimensional echotransponder and biplane fluoroscopic images were recorded on videotape with the catheter at multiple endocardial sites. Catheter location was marked by delivering radiofrequency current to the distal electrode, creating a small endocardial lesion. Catheter location by echo-transponder and by fluoroscopy were compared with lesion location without knowledge of other data. Location by echo-transponder was 8.7 ± 5.1 mm from the center of the radiofrequency lesion versus 14 + 7.8 mm by fluoroscopy (n = 15, p = 0.023). Echo-transponder localization is more precise than is biplane fluoroscopy and may enhance the accuracy of left ventricular eledrophysiologic mapping

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

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    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

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

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    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

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment
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