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The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate. 相似文献
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Bartkova J Horejsí Z Koed K Krämer A Tort F Zieger K Guldberg P Sehested M Nesland JM Lukas C Ørntoft T Lukas J Bartek J 《Nature》2005,434(7035):864-870
During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response. These include phosphorylated kinases ATM and Chk2, and phosphorylated histone H2AX and p53. Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication. Together with genetic analyses, including a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that delays or prevents cancer. Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression. 相似文献
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Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response 总被引:1,自引:1,他引:0
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一台201.5MHz、2MeV、50mA的氘离子射频四极场(RFQ)加速器将用于北京大学中子实验平台。该加速器用4杆型谐振结构,同时为方便水冷采用了微翼型电极。射频结构设计使用了三维电磁场模拟软件Microwave Studio®,并力求满足降低二极场效应和射频功率损耗的要求。文章讨论了优化设计方法并给出一个设计结果。 相似文献
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