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.     

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.     

The planetary increase of brightness during retrograde motion: An explanandum constructed ad explanantem

In Ancient Greek two models were proposed for explaining the planetary motion: the homocentric spheres of Eudoxus and the Epicycle and Deferent System. At least in a qualitative way, both models could explain the retrograde motion, the most challenging phenomenon to be explained using circular motions. Nevertheless, there is another explanandum: during retrograde motion the planets increase their brightness. It is natural to interpret a change of brightness, i.e., of apparent size, as a change in distance. Now, while according to the Eudoxian model the planet is always equidistant from the earth, according to the epicycle and deferent system, the planet changes its distance from the earth, approaching to it during retrograde motion, just as observed. So, it is usually affirmed that the main reason for the rejection of Eudoxus' homocentric spheres in favor of the epicycle and deferent system was that the first cannot explain the manifest planetary increase of brightness during retrograde motion, while the second can. In this paper I will show that this historical hypothesis is not as firmly founded as it is usually believed to be.     

Increasing risk of Amazonian drought due to decreasing aerosol pollution

The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region (Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity. The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern, especially as some general circulation models (GCMs) predict a severe drying of Amazonia in the twenty-first century. Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated with unusually warm North Atlantic sea surface temperatures (SSTs). We show that reduction of dry-season (July-October) rainfall in western Amazonia correlates well with an index of the north-south SST gradient across the equatorial Atlantic (the 'Atlantic N-S gradient'). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth-century multidecadal variability in the Atlantic N-S gradient, provided that the effects of aerosols are included in the model. Simulations for the twenty-first century using the same model show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere.     

Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo

During embryogenesis, cells are spatially patterned as a result of highly coordinated and stereotyped morphogenetic events. In the vertebrate embryo, information on laterality is conveyed to the node, and subsequently to the lateral plate mesoderm, by a complex cascade of epigenetic and genetic events, eventually leading to a left-right asymmetric body plan. At the same time, the paraxial mesoderm is patterned along the anterior-posterior axis in metameric units, or somites, in a bilaterally symmetric fashion. Here we characterize a cascade of laterality information in the zebrafish embryo and show that blocking the early steps of this cascade (before it reaches the lateral plate mesoderm) results in random left-right asymmetric somitogenesis. We also uncover a mechanism mediated by retinoic acid signalling that is crucial in buffering the influence of the flow of laterality information on the left-right progression of somite formation, and thus in ensuring bilaterally symmetric somitogenesis.