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排序方式: 共有194条查询结果,搜索用时 250 毫秒
101.
Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility
Astuti D Morris MR Cooper WN Staals RH Wake NC Fews GA Gill H Gentle D Shuib S Ricketts CJ Cole T van Essen AJ van Lingen RA Neri G Opitz JM Rump P Stolte-Dijkstra I Müller F Pruijn GJ Latif F Maher ER 《Nature genetics》2012,44(3):277-284
Perlman syndrome is a congenital overgrowth syndrome inherited in an autosomal recessive manner that is associated with Wilms tumor susceptibility. We mapped a previously unknown susceptibility locus to 2q37.1 and identified germline mutations in DIS3L2, a homolog of the Schizosaccharomyces pombe dis3 gene, in individuals with Perlman syndrome. Yeast dis3 mutant strains have mitotic abnormalities. Yeast Dis3 and its human homologs, DIS3 and DIS3L1, have exoribonuclease activity and bind to the core RNA exosome complex. DIS3L2 has a different intracellular localization and lacks the PIN domain found in DIS3 and DIS3L1; nevertheless, we show that DIS3L2 has exonuclease activity. DIS3L2 inactivation was associated with mitotic abnormalities and altered expression of mitotic checkpoint proteins. DIS3L2 overexpression suppressed the growth of human cancer cell lines, and knockdown enhanced the growth of these cells. We also detected evidence of DIS3L2 mutations in sporadic Wilms tumor. These observations suggest that DIS3L2 has a critical role in RNA metabolism and is essential for the regulation of cell growth and division. 相似文献
102.
Bodin K Ellmerich S Kahan MC Tennent GA Loesch A Gilbertson JA Hutchinson WL Mangione PP Gallimore JR Millar DJ Minogue S Dhillon AP Taylor GW Bradwell AR Petrie A Gillmore JD Bellotti V Botto M Hawkins PN Pepys MB 《Nature》2010,468(7320):93-97
Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis. 相似文献
103.
104.
Cryptic striations in the upper mantle revealed by hafnium isotopes in southeast Indian ridge basalts 总被引:1,自引:0,他引:1
The Earth's mantle is isotopically heterogeneous on length scales ranging from centimetres to more than 10(4) kilometres. This heterogeneity originates from partial melt extraction and plate tectonic recycling, whereas stirring during mantle convection tends to reduce it. Here we show that mid-ocean ridge basalts from 2,000 km along the southeast Indian ridge (SEIR) display a bimodal hafnium isotopic distribution. This bimodality reveals the presence of ancient compositional striations (streaks) in the Indian Ocean upper mantle. The number density of the streaks is described by a Poisson distribution, with an average thickness of approximately 40 km. Such a distribution is anticipated for a well-stirred upper mantle, in which heterogeneity is continually introduced by plate tectonic recycling, and redistributed by viscous stretching and convective refolding. 相似文献
105.
The supply of some essential metals to pelagic ecosystems is less than the demand, so many phytoplankton have slow rates of photosynthetic production and restricted growth. The types and amounts of metals required by phytoplankton depends on their evolutionary history and on their adaptations to metal availability, which varies widely among ocean habitats. Diatoms, for example, need considerably less iron (Fe) to grow than chlorophyll-b-containing taxa, and the oceanic species demand roughly one-tenth the amount of coastal strains. Like Fe, copper (Cu) is scarce in the open sea, but notably higher concentrations of it are required for the growth of oceanic than of coastal isolates. Here we report that the greater Cu requirement in an oceanic diatom, Thalassiosira oceanica, is entirely due to a single Cu-containing protein, plastocyanin, which--until now--was only known to exist in organisms with chlorophyll b and cyanobacteria. Algae containing chlorophyll c, including the closely related coastal species T. weissflogii, are thought to lack plastocyanin and contain a functionally equivalent Fe-containing homologue, cytochrome c6 (ref. 9). Copper deficiency in T. oceanica inhibits electron transport regardless of Fe status, implying a constitutive role for plastocyanin in the light reactions of photosynthesis in this species. The results suggest that selection pressure imposed by Fe limitation has resulted in the use of a Cu protein for photosynthesis in an oceanic diatom. This biochemical switch reduces the need for Fe and increases the requirement for Cu, which is relatively more abundant in the open sea. 相似文献
106.
107.
Growth and neutralization of the trachoma agent in mouse lungs 总被引:4,自引:0,他引:4
D M Graham 《Nature》1965,207(5004):1379-1380
108.
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
109.
Helium isotope variations in igneous rocks are important for relating isotopic heterogeneity to convective mixing in the Earth's mantle. High 3He/4He ratios at many ocean islands, along with lower and relatively uniform values in mid-ocean-ridge basalts (MORBs), are thought to result from a well mixed upper-mantle source for MORB and a distinct deeper-mantle source for ocean island basalts. At finer scales, 3He/4He variations along mid-ocean ridges have been related to underlying mantle heterogeneity, but relationships between the scales of geochemical segmentation and mantle convection remain enigmatic. Here we present helium isotope data for MORB glasses recovered along approximately 5,800 km of the southeast Indian ridge, and develop an approach to quantitatively relate spatial variations in geochemical and geophysical parameters at the Earth's surface. A point-to-point correlation analysis reveals structure in the helium isotope data at length scales of approximately 150 and approximately 400 km that appears to be related to secondary convection in the underlying mantle. 相似文献
110.