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排序方式: 共有689条查询结果,搜索用时 221 毫秒
351.
352.
Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus 总被引:8,自引:0,他引:8
A T-->G transversion at nt 8993 in mitochondrial DNA of MTATP6 (encoding ATPase 6 of complex V of the respiratory chain) causes impaired mitochondrial ATP synthesis in two related mitochondrial disorders: neuropathy, ataxia and retinitis pigmentosa and maternally inherited Leigh syndrome. To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag. After transfection of human cells, the precursor polypeptide was expressed, imported into and processed within mitochondria, and incorporated into complex V. Allotopic expression of stably transfected constructs in cytoplasmic hybrids (cybrids) homoplasmic with respect to the 8993T-->G mutation showed a significantly improved recovery after growth in selective medium as well as a significant increase in ATP synthesis. This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders. 相似文献
353.
Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis 总被引:4,自引:0,他引:4
354.
Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation 总被引:13,自引:0,他引:13
Lai EC 《Nature genetics》2002,30(4):363-364
355.
Meiotic arrest and aneuploidy in MLH3-deficient mice 总被引:22,自引:0,他引:22
Lipkin SM Moens PB Wang V Lenzi M Shanmugarajah D Gilgeous A Thomas J Cheng J Touchman JW Green ED Schwartzberg P Collins FS Cohen PE 《Nature genetics》2002,31(4):385-390
MutL homolog 3 (Mlh3) is a member of a family of proteins conserved during evolution and having dual roles in DNA mismatch repair and meiosis. The pathway in eukaryotes consists of the DNA-binding components, which are the homologs of the bacterial MutS protein (MSH 2 6), and the MutL homologs, which bind to the MutS homologs and are essential for the repair process. Three of the six homologs of MutS that function in these processes, Msh2, Msh3 and Msh6, are involved in the mismatch repair of mutations, frameshifts and replication errors, and two others, Msh4 and Msh5, have specific roles in meiosis. Of the four MutL homologs, Mlh1, Mlh3, Pms1 and Pms2, three are involved in mismatch repair and at least two, Pms2 and Mlh1, are essential for meiotic progression in both yeast and mice. To assess the role of Mlh3 in mammalian meiosis, we have generated and characterized Mlh3(-/-) mice. Here we show that Mlh3(-/-) mice are viable but sterile. Mlh3 is required for Mlh1 binding to meiotic chromosomes and localizes to meiotic chromosomes from the mid pachynema stage of prophase I. Mlh3(-/-) spermatocytes reach metaphase before succumbing to apoptosis, but oocytes fail to complete meiosis I after fertilization. Our results show that Mlh3 has an essential and distinct role in mammalian meiosis. 相似文献
356.
Casey G Neville PJ Plummer SJ Xiang Y Krumroy LM Klein EA Catalona WJ Nupponen N Carpten JD Trent JM Silverman RH Witte JS 《Nature genetics》2002,32(4):581-583
RNASEL (encoding ribonuclease L) has recently been proposed as a candidate for the hereditary prostate cancer (HPC1) gene. We determined that the RNASEL variant Arg462Gln has three times less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P = 0.007). At least one copy of the mutated allele that causes this substitution is carried by nearly 60% of the men in our study. Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk. 相似文献
357.
Killing activity of neutrophils is mediated through activation of proteases by K+ flux 总被引:34,自引:0,他引:34
Reeves EP Lu H Jacobs HL Messina CG Bolsover S Gabella G Potma EO Warley A Roes J Segal AW 《Nature》2002,416(6878):291-297
According to the hitherto accepted view, neutrophils kill ingested microorganisms by subjecting them to high concentrations of highly toxic reactive oxygen species (ROS) and bringing about myeloperoxidase-catalysed halogenation. We show here that this simple scheme, which for many years has served as a satisfactory working hypothesis, is inadequate. We find that mice made deficient in neutrophil-granule proteases but normal in respect of superoxide production and iodinating capacity, are unable to resist staphylococcal and candidal infections. We also show that activation provokes the influx of an enormous concentration of ROS into the endocytic vacuole. The resulting accumulation of anionic charge is compensated for by a surge of K+ ions that cross the membrane in a pH-dependent manner. The consequent rise in ionic strength engenders the release of cationic granule proteins, including elastase and cathepsin G, from the anionic sulphated proteoglycan matrix. We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria. 相似文献
358.
Giraud E Fardoux J Fourrier N Hannibal L Genty B Bouyer P Dreyfus B Verméglio A 《Nature》2002,417(6885):202-205
Plants use a set of light sensors to control their growth and development in response to changes in ambient light. In particular, phytochromes exert their regulatory activity by switching between a biologically inactive red-light-absorbing form (Pr) and an active far-red-light absorbing form (Pfr). Recently, biochemical and genetic studies have demonstrated the occurrence of phytochrome-like proteins in photosynthetic and non-photosynthetic bacteria--but little is known about their functions. Here we report the discovery of a bacteriophytochrome located downstream from the photosynthesis gene cluster in a Bradyrhizobium strain symbiont of Aeschynomene. The synthesis of the complete photosynthetic apparatus is totally under the control of this bacteriophytochrome. A similar behaviour is observed for the closely related species Rhodopseudomonas palustris, but not for the more distant anoxygenic photosynthetic bacteria of the genus Rhodobacter, Rubrivivax or Rhodospirillum. Unlike other (bacterio)phytochromes, the carboxy-terminal domain of this bacteriophytochrome contains no histidine kinase features. This suggests a light signalling pathway involving direct protein-protein interaction with no phosphorelay cascade. This specific mechanism of regulation may represent an important ecological adaptation to optimize the plant-bacteria interaction. 相似文献
359.
Wakker BP Howk JC Savage BD van Woerden H Tufte SL Schwarz UJ Benjamin R Reynolds RJ Peletier RF Kalberla PM 《Nature》1999,402(6760):388-390
Models of the chemical evolution of the Milky Way suggest that the observed abundances of elements heavier than helium ('metals') require a continuous infall of gas with metallicity (metal abundance) about 0.1 times the solar value. An infall rate integrated over the entire disk of the Milky Way of approximately 1 solar mass per year can solve the 'G-dwarf problem'--the observational fact that the metallicities of most long-lived stars near the Sun lie in a relatively narrow range. This infall dilutes the enrichment arising from the production of heavy elements in stars, and thereby prevents the metallicity of the interstellar medium from increasing steadily with time. However, in other spiral galaxies, the low-metallicity gas needed to provide this infall has been observed only in associated dwarf galaxies and in the extreme outer disk of the Milky Way. In the distant Universe, low-metallicity hydrogen clouds (known as 'damped Ly alpha absorbers') are sometimes seen near galaxies. Here we report a metallicity of 0.09 times solar for a massive cloud that is falling into the disk of the Milky Way. The mass flow associated with this cloud represents an infall per unit area of about the theoretically expected rate, and approximately 0.1-0.2 times the amount required for the whole Galaxy. 相似文献
360.
Zusammenfassung Durch KMnO4-Injektionen hervorgerufene lokale Hautverkalkung kann durch Pyrophosphatinjektionen verhindert werden. Durch alkalische Phosphatase wird die Pyrophosphatwirkung aufgehoben. 相似文献