Construction of a highly enriched marsupial Y chromosome-specific BAC sub-library using isolated Y chromosomes

The Y chromosome is perhaps the most interesting element of the mammalian genome but comparative analysis of the Y chromosome has been impeded by the difficulty of assembling a shotgun sequence of the Y. B AC-based sequencing has been successful for the human and chimpanzee Y but is difficult to do efficiently for an atypical mammalian model species (Skaletsky et al. 2003, Kuroki et al. 2006). We show how Y-specific sub-libraries can be efficiently constructed using DNA amplified from microdissected or flow-sorted Y chromosomes. A Bacterial Artificial Chromosome (BAC) library was constructed from the model marsupial, the tammar wallaby (Macropus eugenii). We screened this library for Y chromosome-derived BAC clones using DNA from both a microdissected Y chromosome and a flow-sorted Y chromosome in order to create a Y chromosome-specific sub-library. We expected that the tammar wallaby Y chromosome should detect ∼100 clones from the 2.2 times redundant library. The microdissected Y DNA detected 85 clones, 82% of which mapped to the Y chromosome and the flow-sorted Y DNA detected 71 clones, 48% of which mapped to the Y chromosome. Overall, this represented a ∼330-fold enrichment for Y chromosome clones. This presents an ideal method for the creation of highly enriched chromosome-specific sub-libraries suitable for BAC-based sequencing of the Y chromosome of any mammalian species

Transcription of a protein-coding gene on B chromosomes of the Siberian roe deer (Capreolus pygargus)

BACKGROUND: Most eukaryotic species represent stable karyotypes with a particular diploid number. B chromosomes are additional to standard karyotypes and may vary in size, number and morphology even between cells of the same individual. For many years it was generally believed that B chromosomes found in some plant, animal and fungi species lacked active genes. Recently, molecular cytogenetic studies showed the presence of additional copies of protein-coding genes on B chromosomes. However, the transcriptional activity of these genes remained elusive. We studied karyotypes of the Siberian roe deer (Capreolus pygargus) that possess up to 14 B chromosomes to investigate the presence and expression of genes on supernumerary chromosomes. RESULTS: Here, we describe a 2 Mbp region homologous to cattle chromosome 3 and containing TNNI3K (partial), FPGT, LRRIQ3 and a large gene-sparse segment on B chromosomes of the Siberian roe deer. The presence of the copy of the autosomal region was demonstrated by B-specific cDNA analysis, PCR assisted mapping, cattle bacterial artificial chromosome (BAC) clone localization and quantitative polymerase chain reaction (qPCR). By comparative analysis of B-specific and non-B chromosomal sequences we discovered some B chromosome-specific mutations in protein-coding genes, which further enabled the detection of a FPGT-TNNI3K transcript expressed from duplicated genes located on B chromosomes in roe deer fibroblasts. CONCLUSIONS: Discovery of a large autosomal segment in all B chromosomes of the Siberian roe deer further corroborates the view of an autosomal origin for these elements. Detection of a B-derived transcript in fibroblasts implies that the protein coding sequences located on Bs are not fully inactivated. The origin, evolution and effect on host of B chromosomal genes seem to be similar to autosomal segmental duplications, which reinforces the view that supernumerary chromosomal elements might play an important role in genome evolution

The HIPASS Catalogue - II. Completeness, Reliability, and Parameter Accuracy

The HI Parkes All Sky Survey (HIPASS) is a blind extragalactic HI 21-cm emission line survey covering the whole southern sky from declination -90 to +25. The HIPASS catalogue (HICAT), containing 4315 HI-selected galaxies from the region south of declination +2, is presented in Meyer et al. (2004a, Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km/s. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux > 8.2 Jy km/s. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width, and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.Comment: Accepted for publication in MNRAS. 12 pages, 11 figures. Paper with higher resolution figures can be downloaded from http://hipass.aus-vo.or

Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction

To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events

Temporal Trends in Medical Therapies for ST- and Non-ST Elevation Myocardial Infarction: (from the Atherosclerosis Risk in Communities [ARIC] Surveillance Study)

Reports from large studies using administrative datasets and event registries have characterized recent temporal trends and treatment patterns for AMI. However, few are population-based and fewer have examined differences in patterns of treatment for patients presenting with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). We examined 22-year trends in the use of 10 medical therapies and procedures by STEMI and NSTEMI classification in 30986 definite or probable MIs in the ARIC Community Surveillance Study from 1987 to 2008. We used weighted multivariable Poisson regression controlling for sex, race/center classification, age, and PREDICT score to estimate average annual percent changes in medical therapy use. From 1987 – 2008, 6106 (19.7%) hospitalized events were classified as STEMI, and 20302 (65.5%) were classified as NSTEMI. Among STEMI patients, increases (%; 95% CI) were noted in the use of ACE inhibitors (6.4; 5.7, 7.2), non-aspirin anti-platelets (5.0; 4.0, 6.0), lipid-lowering medications (4.5; 3.1, 5.8), beta blockers (2.7; 2.4, 3.0), aspirin (1.2; 1.0, 1.3), and heparin (0.8; 0.4, 1.3). Among NSTEMI patients, the use of ACE inhibitors (5.5; 5.0, 6.1), non-aspirin anti-platelets (3.7; 2.7, 4.7), lipid-lowering medications (3.0; 1.9, 4.1), beta blockers (4.2; 3.9, 4.4), aspirin (1.9, 1.6; 2.1), and heparin (1.7; 1.3, 2.1) increased. Among STEMI patients, we observed decreases in the use of thrombolytics (-7.2; -7.9, -6.6) and CABG (-2.4%; -3.6, -1.2). We noted similar increases in PCI and decreases in the use of thrombolytics and CABG among all patients. In conclusion, we found trends of increasing use of evidence-based therapies for both STEMI and NSTEMI patients over the past 22 years

Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

Swift Observations of the highly X-ray variable Narrow Line Seyfert 1 galaxy RX J0148.3-2758

We report on Swift observations of the Narrow-Line Seyfert 1 galaxy (NLS1) RX J0148.3--2758. It was observed for 41.6 ks in 2005 May and for 15.8 ks in 2005 December. On short as well as on long timescales RX J0148.3--2758 is a highly variable source. It doubles its X-ray flux within 18-25 ks. The observation of 2005 December 09, which had a flux 4 times lower than during the 2005 May observations, shows a significant hardening of the X-ray hardness ratio compared with the 2005-May and 2005-December 20/21 observations. A detailed analysis of the X-ray spectra shows that we actually observe two spectral changes in RX J0148.3-2758: First a decrease of the soft X-ray component between 2005 May and December 09, which is most likely due to an increase of the intrinsic absorber column, and second a decrease of the hard X-ray flux in the December 20/21 observations. The soft X-ray spectral slope $\alpha_{\rm X, soft}$=2.58$^{+0.15}_{-0.12}$ during the high state in 2005 May agrees well with that measured by ROSAT (\axs=2.54\plm0.82). In contrast to the strong X-ray variability, the analysis of the Swift UVOT photometry from December 2005 of RX J0148.3--2758 shows no significant variability in any of the 6 UVOT filters. From the simultaneous X-ray and UV observations in 2005 December we measured the X-ray loudness alpha-ox varies between alpha-ox=1.5 and 1.8. Our Swift observations of RX J0148.3-2758 demonstrate the great potential the multi-wavelength observatory Swift has for AGN science. (shortened)Comment: 19 pages; accepted for publication the Astronomical Journa

The Northern HIPASS catalogue - Data presentation, completeness and reliability measures

The Northern HIPASS catalogue (NHICAT) is the northern extension of the HIPASS catalogue, HICAT (Meyer et al. 2004). This extension adds the sky area between the declination range of +2 deg < dec. < +25.5 deg to HICAT's declination range of -90 deg < dec. < +2 deg. HIPASS is a blind HI survey using the Parkes Radio Telescope covering 71% of the sky (including this northern extension) and a heliocentric velocity range of -1,280 km/s to 12,700 km/s . The entire Virgo Cluster region has been observed in the Northern HIPASS. The galaxy catalogue, NHICAT, contains 1002 sources with v_hel > 300 km/s . Sources with -300 km/s < v_hel < 300 km/s were excluded to avoid contamination by Galactic emission. In total, the entire HIPASS survey has found 5317 galaxies identified purely by their HI content. The full galaxy catalogue is publicly-available at .Comment: 12 pages, accepted for publication by MNRA

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

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