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Cardiac defects and renal failure in mice with targeted mutations in Pkd2   总被引:13,自引:0,他引:13  
PKD2, mutations in which cause autosomal dominant polycystic kidney disease (ADPKD), encodes an integral membrane glycoprotein with similarity to calcium channel subunits. We induced two mutations in the mouse homologue Pkd2 (ref.4): an unstable allele (WS25; hereafter denoted Pkd2WS25) that can undergo homologous-recombination-based somatic rearrangement to form a null allele; and a true null mutation (WS183; hereafter denoted Pkd2-). We examined these mutations to understand the function of polycystin-2, the protein product of Pkd2, and to provide evidence that kidney and liver cyst formation associated with Pkd2 deficiency occurs by a two-hit mechanism. Pkd2-/- mice die in utero between embryonic day (E) 13.5 and parturition. They have structural defects in cardiac septation and cyst formation in maturing nephrons and pancreatic ducts. Pancreatic ductal cysts also occur in adult Pkd2WS25/- mice, suggesting that this clinical manifestation of ADPKD also occurs by a two-hit mechanism. As in human ADPKD, formation of kidney cysts in adult Pkd2WS25/- mice is associated with renal failure and early death (median survival, 65 weeks versus 94 weeks for controls). Adult Pkd2+/- mice have intermediate survival in the absence of cystic disease or renal failure, providing the first indication of a deleterious effect of haploinsufficiency at Pkd2on long-term survival. Our studies advance our understanding of the function of polycystin-2 in development and our mouse models recapitulate the complex human ADPKD phenotype.  相似文献   
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Pure TiO2 thin films were deposited onto quartz substrates using a ceramic TiO2 target at an elevated substrate temperature of 573 K by RF magnetron sputtering, and an analysis of structural, optical and photoluminescence characteristics of the films upon phase transformation is reported in this paper. Structural investigations using X-ray diffraction revealed that the as-deposited film was amorphous in nature. Thermal annealing for 2 h at 873 K in air resulted in the formation of anatase phase, and a phase transformation to rutile was observed at 1073 K.An increase in grain size and an improvement in crystallinity were also observed on annealing. Rod- like rutile crystallites were observed in the SEM images of the film annealed at 1273 K. As-deposited films and films annealed up to 1073 K were highly transparent in the visible region with a transparency 480%. Optical band gap of the films decreased upon thermal annealing which is attributed to phase transformation from amorphous to anatase and then to rutile. Optical parameters such as refractive index, optical conductivity and optical dielectric constant increased with increase in annealing temperature. Since rutile is the optically active phase, the superior refractive index of the film annealed at 1073 K along with its high transparency in visible region suggests the application of this film in antireflective coatings. Photoluminescence emission of maximum intensity was observed for the film annealed at 873 K, which exhibits anatase phase. Intense blue emission observed in this film makes it suitable for use in optoelectronic display devices.  相似文献   
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Poisson integer‐valued auto‐regressive process of order 1 (PINAR(1)) due to Al‐Osh and Alzaid (Journal of Time Series Analysis 1987; 8 (3): 261–275) and McKenzie (Advances in Applied Probability 1988; 20 (4): 822–835) has received a significant attention in modelling low‐count time series during the last two decades because of its simplicity. But in many practical scenarios, the process appears to be inadequate, especially when data are overdispersed in nature. This overdispersion occurs mainly for three reasons: presence of some extreme values, large number of zeros, and presence of both extreme values with a large number of zeros. In this article, we develop a zero‐inflated Poisson INAR(1) process as an alternative to the PINAR(1) process when the number of zeros in the data is larger than the expected number of zeros by the Poisson process. We investigate some important properties such as stationarity, ergodicity, autocorrelation structure, and conditional distribution, with a detailed study on h‐step‐ahead coherent forecasting. A comparative study among different methods of parameter estimation is carried out using some simulated data. One real dataset is analysed for practical illustration. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
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设计并合成了一种基于联二萘酚衍生物的荧光传感器1,1在乙腈溶液中对Cu2+具有很好的选择性和灵敏度.当所加金属离子的浓度为1的10倍的时候,只有Cu2+能显著猝灭1的荧光,而其它离子(Hg2+,Pb2+,Sr2+,Ba2+,Cd2+,Ni2+,Co2+,Fe2+,Mn2+,Zn2+,Ce3+,Mg2+,K2+,Fe3+...  相似文献   
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Summary Intravenous pulse injection of neurotensin produces a significant and dose-dependent increase in plasma cholesterol levels in ovariectomized conscious rats, whereas substance P has opposite effect. 4-Aminopyrazolo (3,4,-d) pyrimidine, (4-APP) also significantly lowers plasma cholesterol. The suppressive effects of both substance P and 4-APP were readily reversed by neurotensin, suggesting that the peptides act on hepatic lipoprotein secretion.Supported by grants from the Indian Council of Medical Research (ICMR), New Delhi. K.R. was recipient of a UGC fellowship.  相似文献   
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