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S. Naddaf Dezfuli Zhigang Huan J.M.C. Mol M.A. Lee flang Jiang Chang Jie Zhou 《自然科学进展(英文版)》2014,24(5):531-538
The human body is a buffered environment where p H is effectively maintained. HEPES is a biological buffer often used to mimic the buffering activity of the body in in vitro studies on the degradation behavior of magnesium. However, the influence of HEPES on the degradation behavior of magnesium in the DMEM pseudo-physiological solution has not yet been determined. The research aimed at elucidating the degradation mechanisms of magnesium in DMEM with and without HEPES. The morphologies and compositions of surface layers formed during in vitro degradation tests for 15–3600 s were characterized. The effect of HEPES on the electrochemical behavior and corrosion tendency was determined by performing electrochemical tests. HEPES indeed retained the local p H, leading to intense intergranular/interparticle corrosion of magnesium made from powder and an increased degradation rate. This was attributed to an interconnected network of cracks formed at the original powder particle boundaries and grain boundaries in the surface layer, which provided pathways for the corrosive medium to interact continuously with the internal surfaces and promoted further dissolution. Surface analysis revealed significantly reduced amounts of precipitated calcium phosphates due to the buffering activity of HEPES so that magnesium became less well protected in the buffered environment. 相似文献
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DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected 总被引:8,自引:0,他引:8
Non-coding apurinic/apyrimidinic (AP) sites in DNA are continually created in cells both spontaneously and by damage-specific DNA glycosylases. The biologically critical human base excision repair enzyme APE1 cleaves the DNA sugar-phosphate backbone at a position 5' of AP sites to prime DNA repair synthesis. Here we report three co-crystal structures of human APE1 bound to abasic DNA which show that APE1 uses a rigid, pre-formed, positively charged surface to kink the DNA helix and engulf the AP-DNA strand. APE1 inserts loops into both the DNA major and minor grooves and binds a flipped-out AP site in a pocket that excludes DNA bases and racemized beta-anomer AP sites. Both the APE1 active-site geometry and a complex with cleaved AP-DNA and Mn2+ support a testable structure-based catalytic mechanism. Alanine substitutions of the residues that penetrate the DNA helix unexpectedly show that human APE1 is structurally optimized to retain the cleaved DNA product. These structural and mutational results show how APE1 probably displaces bound glycosylases and retains the nicked DNA product, suggesting that APE1 acts in vivo to coordinate the orderly transfer of unstable DNA damage intermediates between the excision and synthesis steps of DNA repair. 相似文献
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Lorenzen ED Nogués-Bravo D Orlando L Weinstock J Binladen J Marske KA Ugan A Borregaard MK Gilbert MT Nielsen R Ho SY Goebel T Graf KE Byers D Stenderup JT Rasmussen M Campos PF Leonard JA Koepfli KP Froese D Zazula G Stafford TW Aaris-Sørensen K Batra P Haywood AM Singarayer JS Valdes PJ Boeskorov G Burns JA Davydov SP Haile J Jenkins DL Kosintsev P Kuznetsova T Lai X Martin LD McDonald HG Mol D Meldgaard M Munch K Stephan E Sablin M Sommer RS Sipko T Scott E Suchard MA Tikhonov A Willerslev R 《Nature》2011,479(7373):359-364
Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change. 相似文献
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N J de Both M Vermey E van't Hull E Klootwijk-van-Dijke L J van Griensven J N Mol T J Stoof 《Nature》1978,272(5654):626-628
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