861 research outputs found
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
Drug-associated changes in amino acid residues in Gag p2, p7NC, and p6Gag/p6Pol in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response
AbstractRegions of HIV-1 gag between p2 and p6Gag/p6Pol, in addition to protease (PR), develop genetic diversity in HIV-1 infected individuals who fail to suppress virus replication by combination protease inhibitor (PI) therapy. To elucidate functional consequences for viral replication and PI susceptibility by changes in Gag that evolve in vivo during PI therapy, a panel of recombinant viruses was constructed. Residues in Gag p2/p7NC cleavage site and p7NC, combined with residues in the flap of PR, defined novel fitness determinants that restored replicative capacity to the posttherapy virus. Multiple determinants in Gag have a dominant effect on PR phenotype and increase susceptibility to inhibitors of drug-resistant or drug-sensitive PR genes. Gag determinants of drug sensitivity and replication alter the fitness landscape of the virus, and viral replicative capacity can be independent of drug sensitivity. The functional linkage between Gag and PR provides targets for novel therapeutics to inhibit drug-resistant viruses
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 =2.58 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
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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
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