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83.
Understanding why some cellular components are conserved across species but others evolve rapidly is a key question of modern biology. Here we show that in Saccharomyces cerevisiae, proteins organized in cohesive patterns of interactions are conserved to a substantially higher degree than those that do not participate in such motifs. We find that the conservation of proteins in distinct topological motifs correlates with the interconnectedness and function of that motif and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate. 相似文献
84.
Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system 总被引:30,自引:0,他引:30
The development of non-viral gene-transfer technologies that can support stable chromosomal integration and persistent gene expression in vivo is desirable. Here we describe the successful use of transposon technology for the nonhomologous insertion of foreign genes into the genomes of adult mammals using naked DNA. We show that the Sleeping Beauty transposase can efficiently insert transposon DNA into the mouse genome in approximately 5-6% of transfected mouse liver cells. Chromosomal transposition resulted in long-term expression (>5 months) of human blood coagulation factor IX at levels that were therapeutic in a mouse model of haemophilia B. Our results establish DNA-mediated transposition as a new genetic tool for mammals, and provide new strategies to improve existing non-viral and viral vectors for human gene therapy applications. 相似文献
85.
Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation 总被引:20,自引:0,他引:20
Satokata I Ma L Ohshima H Bei M Woo I Nishizawa K Maeda T Takano Y Uchiyama M Heaney S Peters H Tang Z Maxson R Maas R 《Nature genetics》2000,24(4):391-395
The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis. 相似文献
86.
Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification 总被引:10,自引:0,他引:10
Wilkie AO Tang Z Elanko N Walsh S Twigg SR Hurst JA Wall SA Chrzanowska KH Maxson RE 《Nature genetics》2000,24(4):387-390
The genetic analysis of congenital skull malformations provides insight into normal mechanisms of calvarial osteogenesis. Enlarged parietal foramina (PFM) are oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM are usually asymptomatic, but may be associated with headache, scalp defects and structural or vascular malformations of the brain. Inheritance is frequently autosomal dominant, but no causative mutations have been identified in non-syndromic cases. We describe here heterozygous mutations of the homeobox gene MSX2 (located on 5q34-q35) in three unrelated families with PFM. One is a deletion of approximately 206 kb including the entire gene and the others are intragenic mutations of the DNA-binding homeodomain (RK159-160del and R172H) that predict disruption of critical intramolecular and DNA contacts. Mouse Msx2 protein with either of the homeodomain mutations exhibited more than 85% reduction in binding to an optimal Msx2 DNA-binding site. Our findings contrast with the only described MSX2 homeodomain mutation (P148H), associated with craniosynostosis, that binds with enhanced affinity to the same target. This demonstrates that MSX2 dosage is critical for human skull development and suggests that PFM and craniosynostosis result, respectively, from loss and gain of activity in an MSX2-mediated pathway of calvarial osteogenic differentiation. 相似文献
87.
Bacterial photosynthesis in surface waters of the open ocean 总被引:25,自引:0,他引:25
The oxidation of the global ocean by cyanobacterial oxygenic photosynthesis, about 2,100 Myr ago, is presumed to have limited anoxygenic bacterial photosynthesis to oceanic regions that are both anoxic and illuminated. The discovery of oxygen-requiring photosynthetic bacteria about 20 years ago changed this notion, indicating that anoxygenic bacterial photosynthesis could persist under oxidizing conditions. However, the distribution of aerobic photosynthetic bacteria in the world oceans, their photosynthetic competence and their relationship to oxygenic photoautotrophs on global scales are unknown. Here we report the first biophysical evidence demonstrating that aerobic bacterial photosynthesis is widespread in tropical surface waters of the eastern Pacific Ocean and in temperate coastal waters of the northwestern Atlantic. Our results indicate that these organisms account for 2-5% of the photosynthetic electron transport in the upper ocean. 相似文献
88.
Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice 总被引:56,自引:0,他引:56
van der Laan LJ Lockey C Griffeth BC Frasier FS Wilson CA Onions DE Hering BJ Long Z Otto E Torbett BE Salomon DR 《Nature》2000,407(6800):90-94
89.
In metazoans, most pre-messenger RNAs contain introns that are removed by splicing. The spliced mRNAs are then exported to the cytoplasm. Recent studies showed that splicing promotes efficient mRNA export, but the mechanism for coupling these two processes is not known. Here we show that Aly, the metazoan homologue of the yeast mRNA export factor Yralp (ref. 2), is recruited to messenger ribonucleoprotein (mRNP) complexes generated by splicing. In contrast, Aly does not associate with mRNPs assembled on identical mRNAs that already have no introns or with heterogenous nuclear RNP (hnRNP) complexes. Aly is recruited during spliceosome assembly, and then becomes tightly associated with the spliced mRNP. Aly shuttles between the nucleus and cytoplasm, and excess recombinant Aly increases both the rate and efficiency of mRNA export in vivo. Consistent with its splicing-dependent recruitment, Aly co-localizes with splicing factors in the nucleus. We conclude that splicing is required for efficient mRNA export as a result of coupling between the splicing and the mRNA export machineries. 相似文献
90.
The smallest known non-avian theropod dinosaur 总被引:39,自引:0,他引:39
Non-avian dinosaurs are mostly medium to large-sized animals, and to date all known mature specimens are larger than the most primitive bird, Archaeopteryx. Here we report on a new dromaeosaurid dinosaur, Microraptor zhaoianus gen. et sp. nov., from the Early Cretaceous Jiufotang Formation of Liaoning, China. This is the first mature non-avian dinosaur to be found that is smaller than Archaeopteryx, and it eliminates the size disparity between the earliest birds and their closest non-avian theropod relatives. The more bird-like teeth, the Rahonavis-like ischium and the small number of caudal vertebrae of Microraptor are unique among dromaeosaurids and improve our understanding of the morphological transition to birds. The nearly completely articulated foot shows features, such as distally positioned digit I, slender and recurved pedal claws, and elongated penultimate phalanges, that are comparable to those of arboreal birds. The discovery of these in non-avian theropods provides new insights for studying the palaeoecology of some bird-like theropod dinosaurs. 相似文献