scholarly journals Dynamical phase diagram of an auto-regulating gene in fast switching conditions

2020 ◽  
Author(s):  
Chen Jia ◽  
Ramon Grima

AbstractWhile the steady-state behavior of stochastic gene expression with auto-regulation has been extensively studied, its time-dependent behavior has received much less attention. Here, under the assumption of fast promoter switching, we derive and solve a reduced chemical master equation for an auto-regulatory gene circuit with translational bursting and cooperative protein-gene interactions. The analytical expression for the time-dependent probability distribution of protein numbers enables a fast exploration of large swaths of parameter space. For a unimodal initial distribution, we identify three distinct types of stochastic dynamics: (i) the protein distribution remains unimodal at all times; (ii) the protein distribution becomes bimodal at intermediate times and then reverts back to being unimodal at long times (transient bimodality) and (iii) the protein distribution switches to being bimodal at long times. For each of these, the deterministic model predicts either monostable or bistable behaviour and hence there exist six dynamical phases in total. We investigate the relationship of the six phases to the transcription rates, the protein binding and unbinding rates, the mean protein burst size, the degree of cooperativity, the relaxation time to the steady state, the protein mean and the type of feedback loop (positive or negative). We show that transient bimodality is a noise-induced phenomenon that occurs when protein expression is sufficiently bursty and we use theory to estimate the observation time window when it is manifest.

RSC Advances ◽  
2021 ◽  
Author(s):  
Guanzhao Wen ◽  
Xianshao Zou ◽  
Rong Hu ◽  
Jun Peng ◽  
Zhifeng Chen ◽  
...  

Ground- and excited-states properties of N2200 have been studied by steady-state and time-resolved spectroscopies as well as time-dependent density functional theory calculations.


1988 ◽  
Vol 8 (5) ◽  
pp. 1957-1969 ◽  
Author(s):  
R A Shapiro ◽  
D Herrick ◽  
R E Manrow ◽  
D Blinder ◽  
A Jacobson

As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.


1976 ◽  
Vol 231 (4) ◽  
pp. 1033-1038 ◽  
Author(s):  
GM Schoepfle

Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.


2016 ◽  
Vol 20 (6) ◽  
pp. 1413-1431 ◽  
Author(s):  
Joydeep Bhattacharya ◽  
Xue Qiao ◽  
Min Wang

This paper studies the evolution of wealth inequality in an economy with endogenous borrowing constraints. In the model economy, young agents need to borrow to finance human capital investments but cannot commit to repaying their loans. Creditors can punish defaulters by banishing them permanently from the credit market. At equilibrium, loan default is prevented by imposing a borrowing limit tied to the borrower's inheritance. The heterogeneity in inheritances translates into heterogeneity in borrowing limits: endogenously, some borrowers face a zero borrowing limit, and some are partly constrained, whereas others are unconstrained. Depending on the initial distribution of inheritances, it is possible that all lineages are attracted either to the zero-borrowing-limit steady state or to the unconstrained-borrowing steady state—long-run equality. It is also possible that some lineages end up in one steady state and the rest in the other—complete polarization.


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