Biomedical subjects

J Srividhya

Publications and source records attributed to J Srividhya.

4 recordsLinked to original sources

PubMed2006

The effects of time delays in a phosphorylation-dephosphorylation pathway.

Complex signaling cascades involve many interlocked positive and negative feedback loops which have inherent delays. Modeling these complex cascades often requires a large number of variables and parameters. Delay differential equation models have been helpful in describing inherent time lags and also in reducing the number of governing equations. However the consequences of model reduction via delay differential equations have not been fully explored. In this paper we systematically examine the effect of delays in a complex network of phosphorylation-dephosphorylation cycles (described by Gonze and Goldbeter, J. Theor. Biol., 210, (2001) 167-186), which commonly occur in many biochemical pathways. By introducing delays in the positive and negative regulatory interactions, we show that a delay differential model can indeed reduce the number of cycles actually required to describe the phosphorylation-dephosphorylation pathway. In addition, we find some of the unique properties of the network and a quantitative measure of the minimum number of delay variables required to model the network. These results can be extended for modeling complex signalling cascades.

Feedback, Physiological↗

PubMed2006

Why substrate depletion has apparent first-order kinetics in enzymatic digestion.

A number of enzyme digestion assays show apparent first-order kinetics of reactant depletion. There are four possible explanations of this phenomenon: (i) the reaction is dominated by a first-order limiting step, (ii) the digestion follows a pseudo-first-order kinetics under the excess of a reactant species, (iii) the first-order kinetics is only applicable to the slow transient of the reaction, or (iv) the aggregate behavior of the reaction pathway produces behavior indistinguishable from the first-order kinetics. In this paper, we investigate the kinetics for protein digestion by formulating rate equations for two proposed mechanisms, namely the one-by-one mechanism and the zipper mechanism. Our analysis shows that the kinetics of protein digestion follows apparent first-order kinetics irrespective of the mechanism for low initial substrate concentration compared to the initial enzyme concentration. Also, our results provide an explanation for experimental observations and suggest a new experimental protocol that could reveal information on the mechanism of digestion.

Digestion↗

PubMed2006

A simple time delay model for eukaryotic cell cycle.

We propose a seven variable model with time delay in one of the variables for the cell cycle in higher eukaryotes. The model consists of four important phosphorylation-dephosphorylation (P-D) cycles that govern the cell cycle, namely Pre-MPF-MPF, Cdc25P-Cdc25, Wee1P-Wee1 and APCP-APC. Other variables are cyclin, free cyclin dependent kinase (Cdk) and mass. The mass acts as a G2/M checkpoint and the checkpoint is represented by a saddle node loop bifurcation. The key feature of the model is that a time lag has been introduced in the activation of anaphase promoting complex (APC) by maturation promoting factor (MPF). This is effected by treating MPF as a time-delayed variable in the activation step of APC. The time lag acts as a spindle checkpoint. Absence of time delay induces a bistability in our model. Time delay also brings about variability in G1 phase timings. The model also reproduces the mutant phenotype experiments on wee1 cells. Stochasticity has been introduced in the model to simulate the dependence of the cycle time on cell birth length. Mutant phenotypes in the stochastic model reproduce the experimental observations better than the deterministic model.

Animals↗

PubMed2004

Concentration of CO2 over melting ice oscillates.

We report that the concentration of CO2 over melting ice oscillates as long as water and ice coexist. A phenomenological model involving melting of CO2 containing ice leading to its release, readsorption of the vapor on ice, and dissolution in water is proposed. Thermokinetics of these processes lead to nonlinearity of the dynamics. This phenomenon is also observed over impure ice contaminated with salts or in the presence of nitrogen or air. Oscillations have been observed in several other solute or ice-water systems.

Journal Article↗