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201.
Millar CB Guy J Sansom OJ Selfridge J MacDougall E Hendrich B Keightley PD Bishop SM Clarke AR Bird A 《Science (New York, N.Y.)》2002,297(5580):403-405
The mammalian protein MBD4 contains a methyl-CpG binding domain and can enzymatically remove thymine (T) or uracil (U) from a mismatched CpG site in vitro. These properties suggest that MBD4 might function in vivo to minimize the mutability of 5-methylcytosine by removing its deamination product from DNA. We tested this hypothesis by analyzing Mbd4-/- mice and found that the frequency of of C --> T transitions at CpG sites was increased by a factor of three. On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --> TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo. 相似文献
202.
Lambert DM Ritchie PA Millar CD Holland B Drummond AJ Baroni C 《Science (New York, N.Y.)》2002,295(5563):2270-2273
Well-preserved subfossil bones of Adélie penguins, Pygoscelis adeliae, underlie existing and abandoned nesting colonies in Antarctica. These bones, dating back to more than 7000 years before the present, harbor some of the best-preserved ancient DNA yet discovered. From 96 radiocarbon-aged bones, we report large numbers of mitochondrial haplotypes, some of which appear to be extinct, given the 380 living birds sampled. We demonstrate DNA sequence evolution through time and estimate the rate of evolution of the hypervariable region I using a Markov chain Monte Carlo integration and a least-squares regression analysis. Our calculated rates of evolution are approximately two to seven times higher than previous indirect phylogenetic estimates. 相似文献
203.
Debler EW Kaufmann GF Meijler MM Heine A Mee JM Pljevaljcic G Di Bilio AJ Schultz PG Millar DP Janda KD Wilson IA Gray HB Lerner RA 《Science (New York, N.Y.)》2008,319(5867):1232-1235
The blue-emissive antibody EP2-19G2 that has been elicited against trans-stilbene has unprecedented ability to produce bright luminescence and has been used as a biosensor in various applications. We show that the prolonged luminescence is not stilbene fluorescence. Instead, the emissive species is a charge-transfer excited complex of an anionic stilbene and a cationic, parallel pi-stacked tryptophan. Upon charge recombination, this complex generates exceptionally bright blue light. Complex formation is enabled by a deeply penetrating ligand-binding pocket, which in turn results from a noncanonical interface between the two variable domains of the antibody. 相似文献
204.
Stimulation of gonadotropin release by a non-GnRH peptide sequence of the GnRH precursor 总被引:1,自引:0,他引:1
The human gonadotropin-releasing hormone (GnRH) precursor comprises the GnRH sequence followed by an extension of 59 amino acids. Basic amino acid residues in the carboxyl terminal extension may represent sites of processing to biologically active peptides. A synthetic peptide comprising the first 13 amino acids (H X Asp-Ala-Glu-Asn-Leu-Ile-Asp-Ser-Phe-Gln-Glu-Ile-Val X OH) of the 59-amino acid peptide was found to stimulate the release of gonadotropic hormones from human and baboon anterior pituitary cells in culture. The peptide did not affect thyrotropin or prolactin secretion. A GnRH antagonist did not inhibit gonadotropin stimulation by the peptide, and the peptide did not compete with GnRH for GnRH pituitary receptors, indicating that the action of the peptide is independent of the GnRH receptor. The GnRH precursor contains two distinct peptide sequences capable of stimulating gonadotropin release from human and baboon pituitary cells. 相似文献
205.