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Protecting against promiscuity: the regulatory role of insulators 总被引:11,自引:0,他引:11
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G. Geyer M. Biedermann H. -P. Schmidt 《Cellular and molecular life sciences : CMLS》1978,34(3):363-364
Summary Rapid loss of cochlear microphonics in guinea-pigs previously exposed to high-energy impulse noise was shown to be related to the breakdown of the endolymphatic boundary. The cochlear duct was rendered leaky by deterioration of the reticular membrane, and damage of sensory and supporting cells.Aided by grants from the Ministerium für Gesundheitswesen der DDR. 相似文献
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IgH class switching and translocations use a robust non-classical end-joining pathway 总被引:1,自引:0,他引:1
Yan CT Boboila C Souza EK Franco S Hickernell TR Murphy M Gumaste S Geyer M Zarrin AA Manis JP Rajewsky K Alt FW 《Nature》2007,449(7161):478-482
Immunoglobulin variable region exons are assembled in developing B cells by V(D)J recombination. Once mature, these cells undergo class-switch recombination (CSR) when activated by antigen. CSR changes the heavy chain constant region exons (Ch) expressed with a given variable region exon from Cmu to a downstream Ch (for example, Cgamma, Cepsilon or Calpha), thereby switching expression from IgM to IgG, IgE or IgA. Both V(D)J recombination and CSR involve the introduction of DNA double-strand breaks and their repair by means of end joining. For CSR, double-strand breaks are introduced into switch regions that flank Cmu and a downstream Ch, followed by fusion of the broken switch regions. In mammalian cells, the 'classical' non-homologous end joining (C-NHEJ) pathway repairs both general DNA double-strand breaks and programmed double-strand breaks generated by V(D)J recombination. C-NHEJ, as observed during V(D)J recombination, joins ends that lack homology to form 'direct' joins, and also joins ends with several base-pair homologies to form microhomology joins. CSR joins also display direct and microhomology joins, and CSR has been suggested to use C-NHEJ. Xrcc4 and DNA ligase IV (Lig4), which cooperatively catalyse the ligation step of C-NHEJ, are the most specific C-NHEJ factors; they are absolutely required for V(D)J recombination and have no known functions other than C-NHEJ. Here we assess whether C-NHEJ is also critical for CSR by assaying CSR in Xrcc4- or Lig4-deficient mouse B cells. C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks. However, an alternative end-joining pathway, which is markedly biased towards microhomology joins, supports CSR at unexpectedly robust levels in C-NHEJ-deficient B cells. In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations. 相似文献
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Rapid loss of cochlear microphonics in guinea-pigs previously exposed to high-energy impulse noise was shown to be related to the breakdown of the endolymphatic boundary. The cochlear duct was rendered leaky by deterioration of the reticular membrane, and damage of sensory and supporting cells. 相似文献
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Christina Ulm Mona Saffarzadeh Poornima Mahavadi Sandra Müller Gerlinde Prem Farhan Saboor Peter Simon Ralf Middendorff Hildegard Geyer Ingrid Henneke Nils Bayer Susanne Rinné Thomas Lütteke Eva Böttcher-Friebertshäuser Rita Gerardy-Schahn David Schwarzer Martina Mühlenhoff Klaus T. Preissner Andreas Günther Rudolf Geyer Sebastian P. Galuska 《Cellular and molecular life sciences : CMLS》2013,70(19):3695-3708
Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes. 相似文献
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对澄江化石库中Yunnanozoon(云南虫)重新研究表明,其身体由吻、邻和躯干三部发构成;躯干前段为具有成对鳃孔的咽腔,后段为消化区这种独特的身体造型与现生肠鳃类半索动物几无二致,从鸸 有明这个早寒武世动物是地球上半索动物门中书已知最古老的祖先类型。 相似文献
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We present a cointegration analysis on the triangle (USD–DEM, USD–JPY, DEM–JPY) of foreign exchange rates using intra‐day data. A vector autoregressive model is estimated and evaluated in terms of out‐of‐sample forecast accuracy measures. Its economic value is measured on the basis of trading strategies that account for transaction costs. We show that the typical seasonal volatility in high‐frequency data can be accounted for by transforming the underlying time scale. Results are presented for the original and the modified time scales. We find that utilizing the cointegration relation among the exchange rates and the time scale transformation improves forecasting results. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
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Mitchell Y. Sun Melissa Geyer Yulia A. Komarova 《Cellular and molecular life sciences : CMLS》2017,74(22):4189-4207
The endothelium, a monolayer of endothelial cells lining vessel walls, maintains tissue-fluid homeostasis by restricting the passage of the plasma proteins and blood cells into the interstitium. The ion Ca2+, a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca2+ is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP3) messenger facilitates Ca2+ release through IP3 receptors which are Ca2+-selective intracellular channels located within the membrane of the endoplasmic reticulum. Binding of IP3 to the IP3Rs initiates assembly of IP3R clusters, a key event responsible for amplification of Ca2+ signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IP3R clusters, and their specific role in propagation of Ca2+ signals in endothelial cells. 相似文献