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Death patterns resulting from cell cycle-independent cell death. ?

机译:由不依赖细胞周期的细胞死亡导致的死亡模式。

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Drug-induced cell death on the one hand, and dynamics of the cell cycle on the other hand, represent two well-investigated biological principles. As the cell death machinery is highly regulated and depends on a large number of signaling proteins, a connection to the cell cycle is standing to reason. In recent studies, fluorescent cell cycle marker techniques have been combined with longterm microscopy approaches in order to shed light upon a possible cell cycle/cell death dependency for different death-inducing drugs. Here, we present a simple mechanistic model of the null hypothesis where a cell’s cycle does not influence cell death, and calculate death events in different phases of the cell cycle. In a first sample calculation, cells located according to a steady state distribution within the cell cycle are exposed to three different drugs. Dependent on the drug’s mode of action, different death patterns are observed. The second sample calculation considers the exposure of synchronized cell populations to one particular drug. Results show that an increase of cell death in G1can be obtained although cells are initially synchronized in different phases. We conclude that cumulated cell death in one phase can be explained by the stated null hypothesis. Last, the empirical mean and standard deviation are calculated for different sample sizes. Given experimental data, the presented results may help to find out whether the null hypothesis can be rejected.
机译:一方面是药物诱导的细胞死亡,另一方面是细胞周期的动力学,代表了两个经过充分研究的生物学原理。由于细胞死亡机制受到高度调节,并依赖于大量的信号蛋白,因此与细胞周期的联系是合理的。在最近的研究中,荧光细胞周期标记技术已与长期显微镜方法相结合,以阐明不同死亡诱导药物可能的细胞周期/细胞死亡依赖性。在这里,我们提出了一个零假设的简单机制模型,其中细胞周期不影响细胞死亡,并计算了细胞周期不同阶段的死亡事件。在第一样本计算中,将根据细胞周期内稳态分布定位的细胞暴露于三种不同的药物。根据药物的作用方式,观察到不同的死亡方式。第二个样本计算考虑了同步细胞群体对一种特定药物的暴露。结果表明,尽管细胞最初在不同阶段同步,但G1中细胞死亡的增加。我们得出的结论是,一个阶段的累积细胞死亡可以通过所述无效假设来解释。最后,计算不同样本量的经验均值和标准差。在给定实验数据的情况下,给出的结果可能有助于找出是否可以拒绝原假设。

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