Inactivation of the p53 pathway in retinoblastoma

Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.     

Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana

Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes.     

Seismic Performance Assessment of High-rise Buildings Subjected to Near-Fault Ground Motion with Fling Effects

近断层地震地面运动区别于远场地震,具有滑冲效应特性和向前方向性效应特性.其中,具有单方向速度脉冲和阶跃式永久位移的滑冲效应对长周期结构影响较大.取1999年Turkey地震中台站SKR带有滑冲效应的近断层地震记录作为输入获得弹性和弹塑性反应谱,并详细分析具有不同大小线性特征周期的单自由度体系从线性发展到非线性的整个过程中滑冲效应的作用.以某典型的钢筋混凝土剪力墙高层建筑结构为例,具体研究近断层地震滑冲效应对结构抗震性能的影响.结果表明,近断层地震滑冲效应除了对较长周期的高层结构抗震性能具有不利影响之外,对可能产生较大非线性变形的短周期结构的影响同样不可忽视.     

Ecosystem carbon loss with woody plant invasion of grasslands

The invasion of woody vegetation into deserts, grasslands and savannas is generally thought to lead to an increase in the amount of carbon stored in those ecosystems. For this reason, shrub and forest expansion (for example, into grasslands) is also suggested to be a substantial, if uncertain, component of the terrestrial carbon sink. Here we investigate woody plant invasion along a precipitation gradient (200 to 1,100 mm yr(-1)) by comparing carbon and nitrogen budgets and soil delta(13)C profiles between six pairs of adjacent grasslands, in which one of each pair was invaded by woody species 30 to 100 years ago. We found a clear negative relationship between precipitation and changes in soil organic carbon and nitrogen content when grasslands were invaded by woody vegetation, with drier sites gaining, and wetter sites losing, soil organic carbon. Losses of soil organic carbon at the wetter sites were substantial enough to offset increases in plant biomass carbon, suggesting that current land-based assessments may overestimate carbon sinks. Assessments relying on carbon stored from woody plant invasions to balance emissions may therefore be incorrect.     

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.     

大型水电站实时仿真建模方法研究

应用动态大系统模型解耦方法和分割求解法，将大型水电站仿真培训系统的教学模型分解成若干个独立运算的子系统，大大减少了每一时步的计算时间，并将该方法应用到一水电站仿真培训系统。     

A gamma-ray burst with a high-energy spectral component inconsistent with the synchrotron shock model

Gamma-ray bursts are among the most powerful events in nature. These events release most of their energy as photons with energies in the range from 30 keV to a few MeV, with a smaller fraction of the energy radiated in radio, optical, and soft X-ray afterglows. The data are in general agreement with a relativistic shock model, where the prompt and afterglow emissions correspond to synchrotron radiation from shock-accelerated electrons. Here we report an observation of a high-energy (multi-MeV) spectral component in the burst of 17 October 1994 that is distinct from the previously observed lower-energy gamma-ray component. The flux of the high-energy component decays more slowly and its fluence is greater than the lower-energy component; it is described by a power law of differential photon number index approximately -1 up to about 200 MeV. This observation is difficult to explain with the standard synchrotron shock model, suggesting the presence of new phenomena such as a different non-thermal electron process, or the interaction of relativistic protons with photons at the source.