Supporting Online Material Materials and Methods Som Text Figs. S1 to S3 Table S1 References Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops-猫眼课题宝

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A N James;M. J. B. Green;J. R. Paine;A Balmford;K. Gaston;S. Blyth;A. James;V. Kapos;K K Kar

29. 将多个保护区重叠的缓冲区合并进行分析，将306个保护区的样本减少到284个缓冲区。只有一个公园的国家和生态区域被排除在缓冲区中位数增长率的统计分析之外，尽管结果并没有随着它们的纳入而变化。一个简单的相互作用的基因或蛋白质的负反馈循环有可能产生持续的振荡。然而，许多生物振荡器也有一个正反馈回路，这就提出了额外环路带来什么好处的问题。通过计算研究，我们表明通常很难在不影响其幅度的情况下调整负反馈振荡器的频率，而使用正加负反馈，可以实现广泛可调的频率和接近恒定的幅度。这种可调性使得后一种设计适用于需要在一定频率范围内提供恒定输出的生物节律，如心跳和细胞周期。正负振荡器似乎也更健壮，更容易进化，这就解释了为什么它们被发现在可调频率不重要的环境中。哺乳动物心率通常由窦房结测定。该节点以每分钟约50至150个动作电位的可调频率产生恒定振幅的动作电位，这取决于身体的氧气需求。细胞周期振荡器也可能需要这种可调频率和不变振幅的组合。细胞周期的范围从快速分裂的胚胎的约10分钟到快速分裂的体细胞的数十小时（在缓慢分裂的体细胞中更长），但是振荡的振幅变化[活性周期蛋白依赖性激酶-1 （CDK1）的峰值浓度]似乎既不必要也不可取。已经为生物振荡器提出了两种基本类型的电路：(i)包含正反馈和负反馈回路的电路和（ii）仅包含负反馈的电路（表1）（1 - 6）。窦房结振荡器和细胞周期振荡器都属于正负反馈类，这表明这种设计可能更适合产生频率可调、振幅恒定的振荡。我们通过计算研究验证了这一观点，从非洲爪蟾胚胎细胞周期中CDK1振荡的常微分方程模型开始(7)。该模型包括一个负反馈回路[活性CDK1通过后期促进复合体（APC）使其失活]和一对正反馈回路（活性CDK1激活其激活因子Cdc25并使其抑制剂Wee1失活）（图1A）。．．.

29. Overlapping buffers in multiple PAs were combined for analysis, which decreased the sample of 306 PAs to 284 buffer areas. Countries and ecoregions with one park were excluded from statistical analysis of median buffer growth rates, although results did not vary with their inclusion. A simple negative feedback loop of interacting genes or proteins has the potential to generate sustained oscillations. However, many biological oscillators also have a positive feedback loop, raising the question of what advantages the extra loop imparts. Through computational studies, we show that it is generally difficult to adjust a negative feedback oscillator's frequency without compromising its amplitude, whereas with positive-plus-negative feedback, one can achieve a widely tunable frequency and near-constant amplitude. This tunability makes the latter design suitable for biological rhythms like heartbeats and cell cycles that need to provide a constant output over a range of frequencies. Positive-plus-negative oscillators also appear to be more robust and easier to evolve, rationalizing why they are found in contexts where an adjustable frequency is unimportant. T he mammalian heart rate is normally established by the sino-atrial node. The node generates constant-amplitude action potentials at a tunable frequency of ~50 to 150 action potentials per minute, depending on the body's oxygen demands. The cell cycle oscillator may also require this combination of an adjustable frequency and invariant amplitude. The period of the cell cycle ranges from about 10 min in rapidly dividing embryos to tens of hours in rapidly dividing somatic cells (and longer in slowly dividing somatic cells), but variations in the amplitude [the peak concentration of active cyclin-dependent kinase-1 (CDK1)] of the oscillations seem neither necessary nor desirable. Two basic types of circuits have been proposed for biological oscillators: (i) those that contain both positive and negative feedback loops and (ii) those containing only negative feedback (Table 1) (1–6). Both the sino-atrial node oscil-lator and the cell cycle oscillator fall into the positive-plus-negative feedback class, suggesting that this design might be better suited for generating oscillations with a tunable frequency and constant amplitude. We tested this idea through computational studies, beginning with an ordinary differential equation model of CDK1 oscillations in the Xenopus embryonic cell cycle (7). The model includes a negative feedback loop [active CDK1 brings about its inactivation through the anaphase-promoting complex (APC)] and a pair of positive feedback loops (active CDK1 activates its acti-vator Cdc25 and inactivates its inhibitor Wee1) (Fig. 1A). …

Supporting Online Material Materials and Methods Som Text Figs. S1 to S3 Table S1 References Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops

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