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51.
53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility 总被引:1,自引:0,他引:1
Double-strand breaks activate the ataxia telangiectasia mutated (ATM) kinase, which promotes the accumulation of DNA damage factors in the chromatin surrounding the break. The functional significance of the resulting DNA damage foci is poorly understood. Here we show that 53BP1 (also known as TRP53BP1), a component of DNA damage foci, changes the dynamic behaviour of chromatin to promote DNA repair. We used conditional deletion of the shelterin component TRF2 (also known as TERF2) from mouse cells (TRF2(fl/-)) to deprotect telomeres, which, like double-strand breaks, activate the ATM kinase, accumulate 53BP1 and are processed by non-homologous end joining (NHEJ). Deletion of TRF2 from 53BP1-deficient cells established that NHEJ of dysfunctional telomeres is strongly dependent on the binding of 53BP1 to damaged chromosome ends. To address the mechanism by which 53BP1 promotes NHEJ, we used time-lapse microscopy to measure telomere dynamics before and after their deprotection. Imaging showed that deprotected telomeres are more mobile and sample larger territories within the nucleus. This change in chromatin dynamics was dependent on 53BP1 and ATM but did not require a functional NHEJ pathway. We propose that the binding of 53BP1 near DNA breaks changes the dynamic behaviour of the local chromatin, thereby facilitating NHEJ repair reactions that involve distant sites, including joining of dysfunctional telomeres and AID (also known as AICDA)-induced breaks in immunoglobulin class-switch recombination. 相似文献
52.
The amphioxus genome and the evolution of the chordate karyotype 总被引:2,自引:0,他引:2
Putnam NH Butts T Ferrier DE Furlong RF Hellsten U Kawashima T Robinson-Rechavi M Shoguchi E Terry A Yu JK Benito-Gutiérrez EL Dubchak I Garcia-Fernàndez J Gibson-Brown JJ Grigoriev IV Horton AC de Jong PJ Jurka J Kapitonov VV Kohara Y Kuroki Y Lindquist E Lucas S Osoegawa K Pennacchio LA Salamov AA Satou Y Sauka-Spengler T Schmutz J Shin-I T Toyoda A Bronner-Fraser M Fujiyama A Holland LZ Holland PW Satoh N Rokhsar DS 《Nature》2008,453(7198):1064-1071
53.
Disson O Grayo S Huillet E Nikitas G Langa-Vives F Dussurget O Ragon M Le Monnier A Babinet C Cossart P Lecuit M 《Nature》2008,455(7216):1114-1118
The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier. 相似文献
54.
Orton GS Yanamandra-Fisher PA Fisher BM Friedson AJ Parrish PD Nelson JF Bauermeister AS Fletcher L Gezari DY Varosi F Tokunaga AT Caldwell J Baines KH Hora JL Ressler ME Fujiyoshi T Fuse T Hagopian H Martin TZ Bergstralh JT Howett C Hoffmann WF Deutsch LK Van Cleve JE Noe E Adams JD Kassis M Tollestrup E 《Nature》2008,453(7192):196-199
Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-microm methane and 12.2-microm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 +/- 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation. 相似文献
55.
Global trends in emerging infectious diseases 总被引:3,自引:0,他引:3
Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease 'hotspots'). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate. 相似文献
56.
Investigation on regenerator temperature inhomogeneity in Stirling-type pulse tube cooler 总被引:1,自引:0,他引:1
Regenerator is one of the most crucial components to pulse tube cooler (PTC) and thermoacoustic engine. As such regenerator is scaled up to high-power, the thermal and hydrodynamic communication transverse to the acoustic axis gets weaker and weaker. Under this condition, any unsymmetric factor could cause serious instability to the cooler or engine, which degrades their performance. Investigation has been carried out on a high-power two-stage thermal-coupled U-shape Stirling-type PTC. By detailed circumferential temperature measurements along the middle heat exchanger and second stage regen-erator, a kind of temperature inhomogeneity caused by unsymmetric pre-cooling effect of inter-stage thermal bridge was found in the lower part of the regenerator of the PTC. The temperature inhomoge-neity originating from the middle heat exchanger of the second stage regenerator amplified itself in the lower part of the regenerator and then internal streaming formed. The maximal radial temperature dif-ference could reach 30―40 K. Experimental results show that the temperature inhomogeneity intensi-fies with increased pre-cooling power and its direction can be reversed by changing the pre-cooling effect of the first stage PTC to heating effect by using external thermal load. This research shows that it is important to maintain the heating or cooling effects of heat exchangers uniform in high-power re-generative coolers and engines. 相似文献
57.
回热器是脉管制冷机和热声热机中的最关键部件之一. 当回热器由中小功率放大到大功率时, 其内垂直于声传播方向的热力和水力联系变弱. 在这种情况下, 任何的非对称因素都可能在制冷机或发动机的回热器内引发严重的不稳定性问题, 从而降低制冷机或发动机的性能. 对一台大功率二级热耦合U型斯特林脉管制冷机进行了实验研究, 通过对中间换热器和回热器周向温度分布进行测量, 发现了一种由级间预冷不对称性引起的回热器温度不均匀性. 观察发现, 回热器周向的温度不均匀性源于第二级回热器的中间换热器, 之后, 这个温度不均匀性在回热器中以内部直流的形式自行放大, 最大径向温差可达30~40 K. 在对第一级冷头外加热负荷并逐步增大热负荷直至把第一级的预冷效应转变为加热效应的过程中, 回热器内的温度不均性逐渐变弱, 最后其方向发生逆转. 本研究证明了在大功率回热式热机中保持换热器加热或冷却作用周向均一的重要性. 相似文献
58.
J. Marc Macdonald 《Annals of science》2020,77(2):215-252
ABSTRACTEighteenth-century events, replete with Dickensian dualities, brought two Enlightenment families to America. Pierre-Samuel du Pont and Joseph Priestley contemplated relocating their families decades before immigrating. After arriving, they discovered deficiencies in education and chemistry. Their experiences were indicative of the challenges in transmitting transatlantic chemistry. The Priestleys were primed to found an American chemical legacy. Science connected Priestley to British manufacturers, Continental chemists, and American statesmen. Priestley's marriage into the Wilkinson ironmaster dynasty, and Lunar Society membership, helped his sons apprentice, and befriend manufacturer-chemist Thomas Cooper. However, ideological persecution forced them from England. Priestley's plans for his sons to inherit Wilkinson's ironworks evaporated; in America, efforts to establish manufactories, colonies, farms, and a college miscarried. Cooper taught college chemistry, but his materialism provoked dismissals. The Du Ponts were unlikely founders of an industrial-chemistry empire. Du Pont's philosophy promulgated that agriculture, not industry, produced wealth. Eleuthère-Irénée apprenticed in France's gunpowder administration, however, plans for his succession died and director Antoine Lavoisier, a family friend, was executed. E.-I. and Du Pont's arrest precipitated relocation to America. Du Pont's utopian colony and schemes proved unrealistic. Nevertheless, E.-I.'s gunpowder manufactory—utilizing transatlantic contacts and privileged knowledge of advanced French chemistry—succeeded through practical application. 相似文献
59.
Initial sequencing and comparative analysis of the mouse genome 总被引:2,自引:0,他引:2
Mouse Genome Sequencing Consortium Waterston RH Lindblad-Toh K Birney E Rogers J Abril JF Agarwal P Agarwala R Ainscough R Alexandersson M An P Antonarakis SE Attwood J Baertsch R Bailey J Barlow K Beck S Berry E Birren B Bloom T Bork P Botcherby M Bray N Brent MR Brown DG Brown SD Bult C Burton J Butler J Campbell RD Carninci P Cawley S Chiaromonte F Chinwalla AT Church DM Clamp M Clee C Collins FS Cook LL Copley RR Coulson A Couronne O Cuff J Curwen V Cutts T Daly M David R Davies J 《Nature》2002,420(6915):520-562
The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism. 相似文献
60.