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101.
Harris WA 《Science (New York, N.Y.)》1988,240(4849):229
102.
Solomon DA Kim T Diaz-Martinez LA Fair J Elkahloun AG Harris BT Toretsky JA Rosenberg SA Shukla N Ladanyi M Samuels Y James CD Yu H Kim JS Waldman T 《Science (New York, N.Y.)》2011,333(6045):1039-1043
Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer. 相似文献
103.
Miller AD Bezel I Gaffney KJ Garrett-Roe S Liu SH Szymanski P Harris CB 《Science (New York, N.Y.)》2002,297(5584):1163-1166
Ultrafast two-photon photoemission has been used to study electron solvation at two-dimensional metal/polar-adsorbate interfaces. The molecular motion that causes the excess electron solvation is manifested as a dynamic shift in the electronic energy. Although the initially excited electron is delocalized in the plane of the interface, interactions with the adsorbate can lead to its localization. A method for determining the spatial extent of the localized electron in the plane of the interface has been developed. This spatial extent was measured to be on the order of a single adsorbate molecule. 相似文献
104.
105.
Harris FS 《Science (New York, N.Y.)》1914,40(1023):215-216
106.
Murphy WJ Larkin DM Everts-van der Wind A Bourque G Tesler G Auvil L Beever JE Chowdhary BP Galibert F Gatzke L Hitte C Meyers SN Milan D Ostrander EA Pape G Parker HG Raudsepp T Rogatcheva MB Schook LB Skow LC Welge M Womack JE O'brien SJ Pevzner PA Lewin HA 《Science (New York, N.Y.)》2005,309(5734):613-617
The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement. 相似文献
107.
Fernandez-Gonzalez A La Spada AR Treadaway J Higdon JC Harris BS Sidman RL Morgan JI Zuo J 《Science (New York, N.Y.)》2002,295(5561):1904-1906
The classical recessive mouse mutant, Purkinje cell degeneration (pcd), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Here we identify Nna1 as the gene mutated in the original pcd and two additional pcd alleles (pcd2J and pcd3J). Nna1 encodes a putative nuclear protein containing a zinc carboxypeptidase domain initially identified by its induction in spinal motor neurons during axonal regeneration. The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility. 相似文献
108.
Prabhakar S Visel A Akiyama JA Shoukry M Lewis KD Holt A Plajzer-Frick I Morrison H Fitzpatrick DR Afzal V Pennacchio LA Rubin EM Noonan JP 《Science (New York, N.Y.)》2008,321(5894):1346-1350
Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain. 相似文献
109.
Improved surface temperature prediction for the coming decade from a global climate model 总被引:9,自引:0,他引:9
Smith DM Cusack S Colman AW Folland CK Harris GR Murphy JM 《Science (New York, N.Y.)》2007,317(5839):796-799
Previous climate model projections of climate change accounted for external forcing from natural and anthropogenic sources but did not attempt to predict internally generated natural variability. We present a new modeling system that predicts both internal variability and externally forced changes and hence forecasts surface temperature with substantially improved skill throughout a decade, both globally and in many regions. Our system predicts that internal variability will partially offset the anthropogenic global warming signal for the next few years. However, climate will continue to warm, with at least half of the years after 2009 predicted to exceed the warmest year currently on record. 相似文献
110.