271 research outputs found

    Fracture system influence on the reservoirs rock formation of Ordovician-Devonian carbonates in West Siberia tectonic depression

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    During the Paleozoic period from the beginning of the Cambrian to the end of the Carboniferous in the boundaries of the West Siberia tectonic depression there occurred the sea, where the carbonate platforms were formed by the limestones accumulation. All the area at the end of the Carboniferous period was turned to land. Resulting from Gertsynskaya folding in the times of Permian - Triassic the formed deposits were folded and denudated to a considerable extent. Besides, the reservoir rocks of the crust of weathering including redeposited one, were formed as a result of hypergenesis, during the continental stand of the area in the near-surface zone. A new geological prospecting unit has been suggested which underlies these crusts of weathering and formed during fracture tectonic processes with hydrothermal-metasomatic limestones reworking and the processes of hydrothermal leaching and dolomitization. So, in the carbonate platforms the system of fissure zones related to tectonic disturbance was formed. This has a dendrite profile where the series of tangential, more thinned fractures deviate from the stem and finish in pores and caverns. The carbonate platforms formation in the West Siberia tectonic depression has been analyzed, their dynamics and gradual increasing from the minimal in Ordovician and Silurian to maximal at the end of the Late Devonian has been shown

    Variability of Sequence Surrounding the Xist Gene in Rodents Suggests Taxon-Specific Regulation of X Chromosome Inactivation

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    One of the two X chromosomes in female mammalian cells is subject to inactivation (XCI) initiated by the Xist gene. In this study, we examined in rodents (voles and rat) the conservation of the microsatellite region DXPas34, the Tsix gene (antisense counterpart of Xist), and enhancer Xite that have been shown to flank Xist and regulate XCI in mouse. We have found that mouse regions of the Tsix gene major promoter and minisatellite repeat DXPas34 are conserved among rodents. We have also shown that in voles and rat the region homologous to the mouse Tsix major promoter, initiates antisense to Xist transcription and terminates around the Xist gene start site as is observed with mouse Tsix. A conservation of Tsix expression pattern in voles, rat and mice suggests a crucial role of the antisense transcription in regulation of Xist and XIC in rodents. Most surprisingly, we have found that voles lack the regions homologous to the regulatory element Xite, which is instead replaced with the Slc7a3 gene that is unassociated with the X-inactivation centre in any other eutherians studied. Furthermore, we have not identified any transcription that could have the same functions as murine Xite in voles. Overall, our data show that not all the functional elements surrounding Xist in mice are well conserved even within rodents, thereby suggesting that the regulation of XCI may be at least partially taxon-specific

    Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a

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    <p>Abstract</p> <p>Background</p> <p>X chromosome inactivation is the mechanism used in mammals to achieve dosage compensation of X-linked genes in XX females relative to XY males. Chromosome silencing is triggered in <it>cis </it>by expression of the non-coding RNA <it>Xist</it>. As such, correct regulation of the <it>Xist </it>gene promoter is required to establish appropriate X chromosome activity both in males and females. Studies to date have demonstrated co-transcription of an antisense RNA <it>Tsix </it>and low-level sense transcription prior to onset of X inactivation. The balance of sense and antisense RNA is important in determining the probability that a given <it>Xist </it>allele will be expressed, termed the X inactivation choice, when X inactivation commences.</p> <p>Results</p> <p>Here we investigate further the mechanism of <it>Xist </it>promoter regulation. We demonstrate that both sense and antisense transcription modulate <it>Xist </it>promoter DNA methylation in undifferentiated embryonic stem (ES) cells, suggesting a possible mechanistic basis for influencing X chromosome choice. Given the involvement of sense and antisense RNAs in promoter methylation, we investigate a possible role for the RNA interference (RNAi) pathway. We show that the <it>Xist </it>promoter is hypomethylated in ES cells deficient for the essential RNAi enzyme Dicer, but that this effect is probably a secondary consequence of reduced levels of <it>de novo </it>DNA methyltransferases in these cells. Consistent with this we find that Dicer-deficient XY and XX embryos show appropriate <it>Xist </it>expression patterns, indicating that Xist gene regulation has not been perturbed.</p> <p>Conclusion</p> <p>We conclude that <it>Xist </it>promoter methylation prior to the onset of random X chromosome inactivation is influenced by relative levels of sense and antisense transcription but that this probably occurs independent of the RNAi pathway. We discuss the implications for this data in terms of understanding <it>Xist </it>gene regulation and X chromosome choice in random X chromosome inactivation.</p

    Observation of TeV Gamma Rays from the Crab Nebula with Milagro Using a New Background Rejection Technique

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    The recent advances in TeV gamma-ray astronomy are largely the result of the ability to differentiate between extensive air showers generated by gamma rays and hadronic cosmic rays. Air Cherenkov telescopes have developed and perfected the "imaging" technique over the past several decades. However until now no background rejection method has been successfully used in an air shower array to detect a source of TeV gamma rays. We report on a method to differentiate hadronic air showers from electromagnetic air showers in the Milagro gamma ray observatory, based on the ability to detect the energetic particles in an extensive air shower. The technique is used to detect TeV emission from the Crab nebula. The flux from the Crab is estimated to be 2.68(+-0.42stat +- 1.4sys) x10^{-7} (E/1TeV)^{-2.59} m^{-2} s^{-1} TeV^{-1}, where the spectral index is assumed to be as given by the HEGRA collaboration.Comment: 22 pages, 11 figures, submitted to Astrophysical Journa

    A Dual Origin of the Xist Gene from a Protein-Coding Gene and a Set of Transposable Elements

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    X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA

    Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

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    <p>Abstract</p> <p>Background</p> <p>The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8).</p> <p>Results</p> <p>RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation.</p> <p>Conclusion</p> <p>Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.</p

    Measuring extensive air showers with Cherenkov light detectors of the Yakutsk array: The energy spectrum of cosmic rays

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    The energy spectrum of cosmic rays in the range 10^15 eV to 6*10^19 eV has been studied using the air Cherenkov light detectors of the Yakutsk array. The total flux of photons produced by relativistic electrons (including positrons as well, hereafter) of extensive air showers in the atmosphere is used as the energy estimator of the primary particle initiating a shower. The resultant differential flux of cosmic rays exhibits, in accordance with previous measurements, a knee and ankle features at energies 3*10^15 and ~10^19 eV, respectively. A comparison of observational data with simulations is made in the knee and ankle regions in order to choose the models of galactic and extragalactic components of cosmic rays which describe better the energy spectrum measured.Comment: 27 pages, 22 figures, accepted for publication in New Journal of Physics (Focus Issue

    Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials

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    X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals

    Non-invasive measurements of atherosclerosis in adult cystinosis patients

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    Item does not contain fulltextBACKGROUND: Cystinosis is characterized by intralysosomal cystine accumulation, causing end stage renal disease around 10 years of age if not treated with cysteamine. Cystine accumulation in blood vessels might increase atheroma formation or arterial stiffness and therefore increase the risk for cardiovascular disease (CVD). This study aimed to investigate the risk for CVD by non-invasive measures of atherosclerosis (NIMA) and to evaluate the effect of cysteamine treatment. PATIENTS AND METHODS: Thirteen Dutch adult cystinosis patients were included. White blood cell (WBC) cystine levels, glomerular filtration rate (GFR) and concommitant medications were obtained from medical records. NIMA included carotid intima-media thickness (cIMT, n = 13), pulse wave velocity (PWV, n = 8) and pulse wave analysis (PWA, n = 6). Results : GFR ranged between 4-95 mL/min/1.73 m(2). All but one patient were treated with cysteamine, mean WBC cystine values ranged between 0.34-1.64 nmol cystine/mg protein, 8 patients had mean WBC cystine levels <1 nmol cystine/mg protein. When compared to healthy subjects, cIMT and PWV levels were above normal values in 1 patient for each measure. PWA measurements showed high augmentation index in three patients who did not receive lipid-lowering medication. When corrected for renal function, cIMT and PWV levels were within the normal range. CONCLUSION: Young adult cystinosis patients treated with cysteamine have no additional risk for CVD when compared to patients with chronic kidney disease of other causes
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