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41.
The LAR-family protein tyrosine phosphatase sigma (PTPsigma, encoded by the gene Ptprs) consists of a cell adhesion-like extracellular domain composed of immunoglobulin and fibronectin type-III repeats, a single transmembrane domain and two intracellular catalytic domains. It was previously shown to be expressed in neuronal and lung epithelial tissues in a developmentally regulated manner. To study the role of PTPsigma in mouse development, we inactivated Ptprs by gene targeting. All Ptprs+/- mice developed normally, whereas 60% of Ptprs-/- mice died within 48 hours after birth. The surviving Ptprs-/- mice demonstrated stunted growth, developmental delays and severe neurological defects including spastic movements, tremor, ataxic gait, abnormal limb flexion and defective proprioception. Histopathology of brain sections revealed reduction and hypocellularity of the posterior pituitary of Ptprs-/- mice, as well as a reduction of approximately 50-75% in the number of choline acetyl transferase-positive cells in the forebrain. Moreover, peripheral nerve electrophysiological analysis revealed slower conduction velocity in Ptprs-/- mice relative to wild-type or heterozygous animals, associated with an increased proportion of slowly conducting, small-diameter myelinated fibres and relative hypomyelination. By approximately three weeks of age, most remaining Ptprs-/- mice died from a wasting syndrome with atrophic intestinal villi. These results suggest that PTPsigma has a role in neuronal and epithelial development in mice. 相似文献
42.
High-resolution precipitation variations in the Northeast Tibetan Plateau over the last 800 years documented by sediment cores of Qinghai Lake 总被引:5,自引:1,他引:4
ZHANGJiawu JINMing CHENFahu R.W.Battarbee A.CoG.Henderson 《科学通报(英文版)》2003,48(14):1451-1456
Short cores of about 80-cm retrieved from three main basins of th e deepwater areas in Qinghai Lake,the largest inland enclosed lake in China, were studied. Sta-ble isotopes of authigenlc carbonates, grain-size, carbonate and organic matter content at 5-year resolution are used to reconstruct the climatic history over the last 800 years in the Northeastern Tibetan Plateau. Chronology was established according to 210^pb dating and 137^Cs methods and the core corrdation. It is found that cores from different deep basins of the lake can be well correlated. The sedimentary rate is highest in the western basin of the lake and lowest in the east.In the southern basin of the lake where the short core Qing-6is located, the recent average sedimentation rate is 0.1004cm/yr. Variations in effective precipitation recorded by the oxygen isotopes and grain size data durine the last 800 years are consistent with the glacial accumulation record form the Dunde and Guliya ice cores. A dry climate lasted for 300 years from 1200 AD to 1500 AD, followed by a wet period from 1500 to 1560 AD. The two dry periods, 1560 to 1650 AD and 1780 to 1850 AD, were the results of southwest monsoon weakening. The effective precipitation generally increased since 1650 AD due to the strengthening of the Asian South-west Monsoon, resulting in a wet period until the 1950s. Ex-cept the early stage, the Little Ice Age on the Plateau is characterized b y increased effective moisture. Organic mat-ter content, with nearly 200-year cycles, shows similar trend with the atmospheric delta earbon-14 before the 1850s, indi-eating that the bioproductivity responds to solar activity. 相似文献
43.
The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair 总被引:17,自引:0,他引:17
Hopfner KP Craig L Moncalian G Zinkel RA Usui T Owen BA Karcher A Henderson B Bodmer JL McMurray CT Carney JP Petrini JH Tainer JA 《Nature》2002,418(6897):562-566
The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. These functions all imply that the linked binding of two DNA substrates occurs, although the molecular basis for this process remains unknown. Here we present a 2.2 A crystal structure of the Rad50 coiled-coil region that reveals an unexpected dimer interface at the apex of the coiled coils in which pairs of conserved Cys-X-X-Cys motifs form interlocking hooks that bind one Zn(2+) ion. Biochemical, X-ray and electron microscopy data indicate that these hooks can join oppositely protruding Rad50 coiled-coil domains to form a flexible bridge of up to 1,200 A. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain. The Rad50 hook is functional, because mutations in this motif confer radiation sensitivity in yeast and disrupt binding at the distant Mre11 nuclease interface. These data support an architectural role for the Rad50 coiled coils in forming metal-mediated bridging complexes between two DNA-binding heads. The resulting assemblies have appropriate lengths and conformational properties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining. 相似文献
44.
全新世早期强降温事件的古里雅冰芯记录证据 总被引:20,自引:1,他引:20
根据古里雅冰芯记录,揭示出全新世早期存在两次低温事件,并且其发生年代(9.4和8.2kaBP左右)与全新世早期北大西洋的两次冰筏事件年代相一致。其中后一代低温事件(即“8.2kaBP冷事件)”极为显著,并表现出迅速降温、缓慢升温的明显特征,最冷时降温幅度达7.8-10℃,大于格陵兰冰芯记录中该冷事件的降温幅度。这反映了青藏高原地区对于气候变化的敏感性。弱的太阳活动和弱的热盐环流是“8.2kaBP冷事件”发生的关键原因。 相似文献
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de Bakker PI Burtt NP Graham RR Guiducci C Yelensky R Drake JA Bersaglieri T Penney KL Butler J Young S Onofrio RC Lyon HN Stram DO Haiman CA Freedman ML Zhu X Cooper R Groop L Kolonel LN Henderson BE Daly MJ Hirschhorn JN Altshuler D 《Nature genetics》2006,38(11):1298-1303
A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world. 相似文献
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Stacey SN Manolescu A Sulem P Rafnar T Gudmundsson J Gudjonsson SA Masson G Jakobsdottir M Thorlacius S Helgason A Aben KK Strobbe LJ Albers-Akkers MT Swinkels DW Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Godino J Garcia-Prats MD Polo E Tres A Mouy M Saemundsdottir J Backman VM Gudmundsson L Kristjansson K Bergthorsson JT Kostic J Frigge ML Geller F Gudbjartsson D Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Jonsson T von Holst S 《Nature genetics》2007,39(7):865-869
Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone. 相似文献