Biomedical subjects

Steven J Cox

Publications and source records attributed to Steven J Cox.

7 recordsLinked to original sources

PubMed2006

A kinetic model of oxygen regulation of cytochrome production in Escherichia coli.

Recent experimental work has identified the principal components arrayed by Escherichia coli in its sensing of, and response to, varying levels of oxygen. This apparatus may be leveraged/modified by the metabolic engineer to identify nonuniform oxygen and glucose regimens that deliver better yields than their uniform counterparts. Toward this end we build and analyse a mathematical model that captures the role played by oxygen in the regulation of cytochrome production in E. coli.

Benzoquinones↗

PubMed2006

An adjoint method for channel localization.

Single cells learn by tuning their synaptic conductances and redistributing their excitable machinery. To reveal its learning rules, one must therefore know how the cell remaps its ion channels in response to physiological stimuli. We here develop an adjoint approach for discerning the non-uniform distribution of a given channel type from knowledge of the time course of membrane potential at two distinct locations following a prescribed injection of current.

Algorithms↗

PubMed2005

Development of a metabolic network design and optimization framework incorporating implementation constraints: a succinate production case study.

We have developed a pathway design and optimization scheme that accommodates genetically and/or environmentally derived operational constraints. We express the full set of theoretically optimal pathways in terms of the underlying elementary flux modes and then examine the sensitivity of the optimal yield to a wide class of physiological perturbations. Though the scheme is general it is best appreciated in a concrete context: we here take succinate production as our model system. The scheme produces novel pathway designs and leads to the construction of optimal succinate production pathway networks. The model predictions compare very favorably with experimental observations.

Computer Simulation↗

PubMed2005

Genetically constrained metabolic flux analysis.

Significant progress has been made in using existing metabolic databases to estimate metabolic fluxes. Traditional metabolic flux analysis generally starts with a predetermined metabolic network. This approach has been employed successfully to analyze the behaviors of recombinant strains by manually adding or removing the corresponding pathway(s) in the metabolic map. The current work focuses on the development of a new framework that utilizes genomic and metabolic databases, including available genetic/regulatory network structures and gene chip expression data, to constrain metabolic flux analysis. The genetic network consisting of the sensing/regulatory circuits will activate or deactivate a specific set of genes in response to external stimulus. The activation and/or repression of this set of genes will result in different gene expression levels that will in turn change the structure of the metabolic map. Hence, the metabolic map will automatically "adapt" to the external stimulus as captured by the genetic network. This adaptation selects a subnetwork from the pool of feasible reactions and so performs what we term "environmentally driven dimensional reduction." The Escherichia coli oxygen and redox sensing/regulatory system, which controls the metabolic patterns connected to glycolysis and the TCA cycle, was used as a model system to illustrate the proposed approach.

Citric Acid Cycle↗

PubMed2004

Recovering the passive properties of tapered dendrites from single and dual potential recordings.

We demonstrate that measurement of the membrane potential at one or more sites on a branched and tapered neuron following a known transient injection of subthreshold somatic current uniquely determines the cell's passive electrical properties. That is, knowledge of the potentials allows recovery of the cell's axial resistance, membrane capacitance, membrane conductance and soma conductance. The argument underlying uniqueness leads immediately to a constructive, robust algorithm that we successfully test on synthetic data. The robustness stems from the fact that the algorithm requires only a few weighted integrals, or moments, of the measured potentials.

Algorithms↗

PubMed2002

Estimating the time course of pore expansion during the spike phase of exocytotic release in mast cells of the beige mouse.

Our objective is to determine the time course of exocytotic fusion pore opening (P) in mast cells of the beige mouse from the measured efflux of the spike phase of exocytotic release (J). We show that a pore whose meridian or radius grows linearly with time cannot reproduce the efflux. We also show that a pore that opens very quickly [relative to the diffusivity of 5-hydroxytryptamine (5-HT)] and completely (P = pi) also does not mimic the experimental efflux, and estimate maximum pore angles of 70 (+/- 20) degrees. We show that a larger class of opening functions reproduces the rising phase and part of the decay phase and calculate pore expansion rate, pore radius and pore angle, none of which can be readily measured. In the initial stages of the spike phase (50-200 ms) when the gel matrix has not expanded significantly, this model suggests that the pore radius increases exponentially with a time constant of 82(+/- 62) ms with pore expansion reaching its maximum velocity of 20 (+/- 7) nm ms-1. We conclude that the release process is dynamic and suggest that the velocity of pore opening (V) and the diffusivity of 5-HT (D), in addition to the size of the vesicle (R, radius), vary with time. We discuss assumptions and improvements to the model and propose that this methodology is applicable for determining P from measured J in other endocrine cells and neurons when D within the secretory vesicle is much less than D within the pore neck.

Animals↗

PubMedDate not supplied

Estimating the location and time course of synaptic input from multi-site potential recordings.

A method is introduced that permits accurate and robust extraction of the location and time course of synaptic conductance from potentials recorded on either side of, and perhaps at some distance from, the synapse in question. It is shown that such data permits one to fully overcome the problems typically associated with lack of spaceclamp. The method does not presume anything about the nature of the time course and yet is applicable to branched, active cells receiving simultaneous input from a number of synapses.

Action Potentials↗