排序方式: 共有2条查询结果,搜索用时 66 毫秒
1
1.
Hoffmann K Dreger CK Olins AL Olins DE Shultz LD Lucke B Karl H Kaps R Müller D Vayá A Aznar J Ware RE Sotelo Cruz N Lindner TH Herrmann H Reis A Sperling K 《Nature genetics》2002,31(4):410-414
Pelger-Hu?t anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy and skeletal abnormalities. Homozygous offspring in an extinct rabbit lineage showed severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortality. Here we show, by carrying out a genome-wide linkage scan, that PHA is linked to chromosome 1q41-43. We identified four splice-site, two frameshift and two nonsense mutations in LBR, encoding the lamin B receptor. The lamin B receptor (LBR), a member of the sterol reductase family, is evolutionarily conserved and integral to the inner nuclear membrane; it targets heterochromatin and lamins to the nuclear membrane. Lymphoblastoid cells from heterozygous individuals affected with PHA show reduced expression of the lamin B receptor, and cells homozygous with respect to PHA contain only trace amounts of it. We found that expression of the lamin B receptor affects neutrophil nuclear shape and chromatin distribution in a dose-dependent manner. Our findings have implications for understanding nuclear envelope-heterochromatin interactions, the pathogenesis of Pelger-like conditions in leukemia, infection and toxic drug reactions, and the evolution of neutrophil nuclear shape. 相似文献
2.
Survey‐based indicators are widely seen as leading indicators for economic activity. As such, consumer confidence might be informative for the future path of private consumption. Although the indicators receive high attention in the media, their forecasting power often appears to be very limited. This paper takes a fresh look at the data that serve as a basis for the consumer confidence indicator (CCI) reported by the EU Commission for the euro area. Different pooling methods are applied to exploit the survey information. Forecasts are based on mixed data sampling (MIDAS) and bridge equations. While the CCI does not outperform the autoregressive benchmark, the new indicators are able to raise forecasting performance. The best performing indicator should be built upon pre‐selection methods. Data‐driven aggregation methods should be preferred to determine the weights of the individual ingredients. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
1