Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing

Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and increased neoplasia incidence. Here we evaluate the functional interaction of Atm and telomeres in vivo. We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc). These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multi-organ system compromise, accelerated ageing and premature death. We show that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of A-T pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves.     

Mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform

When recombinant and cellular prion protein (PrP(C)) binds copper, it acquires properties resembling the scrapie isoform (PrP(Sc)), namely protease resistance, detergent insolubility and increased beta sheet content. However, whether the conformations of PrP(C) induced by copper and PrP(Sc) are similar has not been studied in great detail. Here, we use a panel of seven monoclonal antibodies to decipher the epitopes on full-length mouse PrP(C) that are affected by exogenous copper, and to compare the antigenicity of the copper-treated full-length PrP(C) with the full-length PrP(Sc) present in scrapie-infected mouse brains. In the presence of copper, we found that epitopes along residues 115-130 and 153-165 become more accessible on PrP(C). These regions correspond to the two beta sheet strands in recombinant PrP and they were proposed to be important for prion conversion. However, when we compared the antibody-binding patterns between full-length PrP(C) with full-length PrP(Sc) and between copper-treated full-length PrP(C) with full-length PrP(Sc), antibody binding to residues 143-155 and 175-185 was consistently increased on PrP(Sc). Collectively, our results suggest that copper-treated full-length PrP(C) does not resemble full-length PrP(Sc), despite acquiring PrP(Sc)-like properties. In addition, since each full-length protein reacts distinctively to some of the antibodies, this binding pattern could discriminate between PrP(C) and PrP(Sc).     

对-二苯氨基苯基硼酸的光谱及光物理行为研究

利用紫外可见吸收光谱和荧光光谱对新合成的化合物：对-二苯氨基苯基硼酸(DPBA，三苯胺衍生物)在不同极性介质中的光谱、光物理行为进行了研究，并利用Lippert-Mataga方程计算了该化合物基态和激发态偶极矩间的差值△μ=3．0D．实验结果表明，溶剂极性对DPBA的吸收光谱峰位和峰形产生相对较小的影响，而使DPBA荧光光谱发生较大的红移，荧光峰的半峰宽变宽且基态和激发态间的偶极矩差值△μ变大，表明了该化合物具有典型的分子内电荷转移(ICT)的特性．     

硅单晶微缺陷的激光荧光显示

用室温激光荧光显微技术直接观察了硅单晶中的微缺陷,获得了能与择优腐蚀相对应的微缺陷形貌图.实验表明,激光荧光显微可望发展成为一种无接触、非破坏、高灵敏的硅中微缺陷的显示技术.     

Altered brain response to verbal learning following sleep deprivation

The effects of sleep deprivation on the neural substrates of cognition are poorly understood. Here we used functional magnetic resonance imaging to measure the effects of 35 hours of sleep deprivation on cerebral activation during verbal learning in normal young volunteers. On the basis of a previous hypothesis, we predicted that the prefrontal cortex (PFC) would be less responsive to cognitive demands following sleep deprivation. Contrary to our expectations, however, the PFC was more responsive after one night of sleep deprivation than after normal sleep. Increased subjective sleepiness in sleep-deprived subjects correlated significantly with activation of the PFC. The temporal lobe was activated after normal sleep but not after sleep deprivation; in contrast, the parietal lobes were not activated after normal sleep but were activated after sleep deprivation. Although sleep deprivation significantly impaired free recall compared with the rested state, better free recall in sleep-deprived subjects was associated with greater parietal lobe activation. These findings show that there are dynamic, compensatory changes in cerebral activation during verbal learning after sleep deprivation and implicate the PFC and parietal lobes in this compensation.