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321.
Postel-Vinay S Véron AS Tirode F Pierron G Reynaud S Kovar H Oberlin O Lapouble E Ballet S Lucchesi C Kontny U González-Neira A Picci P Alonso J Patino-Garcia A de Paillerets BB Laud K Dina C Froguel P Clavel-Chapelon F Doz F Michon J Chanock SJ Thomas G Cox DG Delattre O 《Nature genetics》2012,44(3):323-327
Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2. 相似文献
322.
Sylvie Elsen Véronique Collin-Faure Xavier Gidrol Claudie Lemercier 《Cellular and molecular life sciences : CMLS》2013,70(22):4385-4397
Highly hazardous DNA double-strand breaks can be induced in eukaryotic cells by a number of agents including pathogenic bacterial strains. We have investigated the genotoxic potential of Pseudomonas aeruginosa, an opportunistic pathogen causing devastating nosocomial infections in cystic fibrosis or immunocompromised patients. Our data revealed that infection of immune or epithelial cells by P. aeruginosa triggered DNA strand breaks and phosphorylation of histone H2AX (γH2AX), a marker of DNA double-strand breaks. Moreover, it induced formation of discrete nuclear repair foci similar to gamma-irradiation-induced foci, and containing γH2AX and 53BP1, an adaptor protein mediating the DNA-damage response pathway. Gene deletion, mutagenesis, and complementation in P. aeruginosa identified ExoS bacterial toxin as the major factor involved in γH2AX induction. Chemical inhibition of several kinases known to phosphorylate H2AX demonstrated that Ataxia Telangiectasia Mutated (ATM) was the principal kinase in P. aeruginosa-induced H2AX phosphorylation. Finally, infection led to ATM kinase activation by an auto-phosphorylation mechanism. Together, these data show for the first time that infection by P. aeruginosa activates the DNA double-strand break repair machinery of the host cells. This novel information sheds new light on the consequences of P. aeruginosa infection in mammalian cells. As pathogenic Escherichia coli or carcinogenic Helicobacter pylori can alter genome integrity through DNA double-strand breaks, leading to chromosomal instability and eventually cancer, our findings highlight possible new routes for further investigations of P. aeruginosa in cancer biology and they identify ATM as a potential target molecule for drug design. 相似文献
323.
N. -E. Andén B.-E. B. -E. Roos B. Werdinius 《Cellular and molecular life sciences : CMLS》1963,19(7):359-360
Zusammenfassung Es wird papierchromatographisch gezeigt, dass Cerebrospinalflüssigkeit gesunder Menschen sowohl Homovanillinsäure als auch 3-Methoxy-4-hydroxymandelsäure enthält. Die Konzentration der ersteren ist etwa 75 ng/ml und die der letzteren etwa 25 ng/ml.
Acknowledgment. This work has been supported by grants from Leo Ltd., Hälsingborg, and from the Medical Faculty, University of Göteborg (Sweden). For technical assistance we are indebted to Mrs.I. Olofson. 相似文献
Acknowledgment. This work has been supported by grants from Leo Ltd., Hälsingborg, and from the Medical Faculty, University of Göteborg (Sweden). For technical assistance we are indebted to Mrs.I. Olofson. 相似文献
324.
Gehrels N Norris JP Barthelmy SD Granot J Kaneko Y Kouveliotou C Markwardt CB Mészáros P Nakar E Nousek JA O'Brien PT Page M Palmer DM Parsons AM Roming PW Sakamoto T Sarazin CL Schady P Stamatikos M Woosley SE 《Nature》2006,444(7122):1044-1046
Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at approximately 2 s. Long-duration bursts originate from star-forming regions in galaxies, have accompanying supernovae when these are near enough to observe and are probably caused by massive-star collapsars. Recent observations show that short-duration bursts originate in regions within their host galaxies that have lower star-formation rates, consistent with binary neutron star or neutron star-black hole mergers. Moreover, although their hosts are predominantly nearby galaxies, no supernovae have been so far associated with short-duration GRBs. Here we report that the bright, nearby GRB 060614 does not fit into either class. Its approximately 102-s duration groups it with long-duration GRBs, while its temporal lag and peak luminosity fall entirely within the short-duration GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short-duration GRBs. This combination of a long-duration event without an accompanying supernova poses a challenge to both the collapsar and the merging-neutron-star interpretations and opens the door to a new GRB classification scheme that straddles both long- and short-duration bursts. 相似文献
325.
从科、属 2个层次对河北省盐生植物区系进行了统计分析 ,得出如下结论 :(1)盐生植物共计有 2 5科、6 2属、91种 ;(2 )植物区系基本上属于温带性质 ;(3)特有现象无 相似文献
326.
327.
Hemoglobin is widely used as an inhibitor of EDRF effects. Hemoglobin contracts pig coronary arteries in vitro. However, during this contraction, effects of substance P and bradykinin which act via the EDRF are not inhibited. This means that the hemoglobin contraction is not caused by inhibition of the EDRF. This contraction is caused by a substance released from the endothelium, and by eicosano?ds released from the smooth muscles. 相似文献
328.
Consequences of acute ischemia for the electrical and mechanical function of the ventricular myocardium. A brief review 总被引:1,自引:0,他引:1
A G Kléber 《Experientia》1990,46(11-12):1162-1167
Reduction or interruption of the blood supply to the myocardium leads to marked disturbances of electrical and mechanical function within a few seconds. Electrical dysfunction is characterized by an initial depolarization of the resting membrane, and a decrease of the amplitude, the upstroke velocity and the duration of the action potential. Both depolarization and depression of the action potential are closely associated with intracellular metabolic acidosis. After this initial phase, electrical cell-to-cell uncoupling develops, probably as a consequence of increased cytosolic free [Ca++]. Mechanical dysfunction is characterized by a dissociation of the initial decrease of active force development from the subsequent ischemic contracture. Active force development in acute ischemia is inhibited by the accumulation of ischemic metabolic products (H+, inorganic phosphate (Pi), Mg++) but not by a marked decrease of [ATP]. The subsequent ischemic contracture is probably initiated by release of Ca++ from intracellular stores. This release causes rapid consumption of ATP and the development of rigor within 1-2 minutes. 相似文献
329.
330.