The tumor suppressor p53 mediates the cellular response to various stresses. It was experimentally shown that the concentration of p53 can show oscillations with short or long periods upon DNA damage. The underlying m...The tumor suppressor p53 mediates the cellular response to various stresses. It was experimentally shown that the concentration of p53 can show oscillations with short or long periods upon DNA damage. The underlying mechanism for this phenomenon is still not fully understood. Here, we construct a network model comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops and ATM autoactivation. We recapitulate the typical features of p53 oscillations including p53 birhythmicity. We show the dependence of p53 birhythmicity on various factors such as the phosphorylation status of ATM. We also perform stochastic simulation and find the noise-induced transitions between two modes of p53 oscillation, which increases the p53 variability in both the amplitude and period. These results suggest that p53 birhythmicity enhances the responsiveness of p53 network, which may facilitate its tumor suppressive function.展开更多
Two kinds of different mechanistic oscillations can be displayed in the H_2O_2-KSCN-CuSO_4-NaOH system. One discovered by this study is the pH oscillation in a continuous flow stirred tank reactor(CSTR) resulting from...Two kinds of different mechanistic oscillations can be displayed in the H_2O_2-KSCN-CuSO_4-NaOH system. One discovered by this study is the pH oscillation in a continuous flow stirred tank reactor(CSTR) resulting from the oxidation of KSCN. The other is the oscillation of H_2O_2 decomposition in both CSTR and batch reactors(reported by Orbáin in 1986). Under appropriate experimental conditions, the system exhibits a birhythmicity in a CSTR. Two different pH oscillations are reported here. The pH oscillations which accompany the decomposition of H_2O_2 exist in the batch reactor and the CSTR at a high flowrate, but the pH oscillations in a CSTR at a low flowrate originates from proton positive and negative feedback in the oxidation of KSCN. The oscillation of non-catalyzed oxidation of KSCN by hydrogen peroxide in a CSTR can be found. Also we have observed whether Cu^(2+) exists or not in the batch system, the pH increases to near neutral ultimately after pH drops twice.展开更多
An autocatalytic biochemical system in the presence of recycling enzyme is solved numerically using two numerical methods based on finite difference schemes. The first method is the well known Euler method which is an...An autocatalytic biochemical system in the presence of recycling enzyme is solved numerically using two numerical methods based on finite difference schemes. The first method is the well known Euler method which is an explicit method, whereas the second method is implicit. Although the implicit method, method 2, is first-order accurate in time it converges to the fixed point（s） for large time step, L Numerical results show the existence of hard excitation and birhythmicity.展开更多
基金Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant Nos.16KJB180007 and 16KJB140014)the Special Foundation of Theoretical Physics Research Program of China(Grant No.11547025)the National Natural Science Foundation of China(Grant No.11574139)
文摘The tumor suppressor p53 mediates the cellular response to various stresses. It was experimentally shown that the concentration of p53 can show oscillations with short or long periods upon DNA damage. The underlying mechanism for this phenomenon is still not fully understood. Here, we construct a network model comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops and ATM autoactivation. We recapitulate the typical features of p53 oscillations including p53 birhythmicity. We show the dependence of p53 birhythmicity on various factors such as the phosphorylation status of ATM. We also perform stochastic simulation and find the noise-induced transitions between two modes of p53 oscillation, which increases the p53 variability in both the amplitude and period. These results suggest that p53 birhythmicity enhances the responsiveness of p53 network, which may facilitate its tumor suppressive function.
基金Supported by NSFC(29573109) and Research fund of CUMT.
文摘Two kinds of different mechanistic oscillations can be displayed in the H_2O_2-KSCN-CuSO_4-NaOH system. One discovered by this study is the pH oscillation in a continuous flow stirred tank reactor(CSTR) resulting from the oxidation of KSCN. The other is the oscillation of H_2O_2 decomposition in both CSTR and batch reactors(reported by Orbáin in 1986). Under appropriate experimental conditions, the system exhibits a birhythmicity in a CSTR. Two different pH oscillations are reported here. The pH oscillations which accompany the decomposition of H_2O_2 exist in the batch reactor and the CSTR at a high flowrate, but the pH oscillations in a CSTR at a low flowrate originates from proton positive and negative feedback in the oxidation of KSCN. The oscillation of non-catalyzed oxidation of KSCN by hydrogen peroxide in a CSTR can be found. Also we have observed whether Cu^(2+) exists or not in the batch system, the pH increases to near neutral ultimately after pH drops twice.
文摘An autocatalytic biochemical system in the presence of recycling enzyme is solved numerically using two numerical methods based on finite difference schemes. The first method is the well known Euler method which is an explicit method, whereas the second method is implicit. Although the implicit method, method 2, is first-order accurate in time it converges to the fixed point（s） for large time step, L Numerical results show the existence of hard excitation and birhythmicity.
