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Biomedical subjects

L A Segel

Publications and source records attributed to L A Segel.

At least 55 records · Page 3Linked to original sources

Models of the influence of predation on aspect diversity in prey populations.

By considering a model incorporating behavioral changes by predators and prey evolution, we demonstrate how under certain conditions apostatic predation influences the maintenance of diversity within prey populations, and among different prey species. Further, we estimate the intrinsic "diversity" wavelength of the system when apostasy combines with other factors to lead to nonuniform distributions of prey along aspect gradients.

Animals↗

Control of developmental transitions in the cyclic AMP signalling system of Dictyostelium discoideum.

In the first few hours after starvation, the developing cAMP secretory system in Dictyostelium discoideum has been observed to be successively in one of four states: (a) quiescent, (b) excitable (capable of relay), (c) autonomously oscillating, and (d) secreting at a high steady level. A theoretical model is presented which demonstrates that the proximal cause of the transitions between different types of behavior may be slow changes in the activities of the enzymes adenylate cyclase and phosphodiesterase. These changes affect the stability properties of the steady state admitted by the cAMP signalling system. Sustained oscillations develop when the steady state is unstable, whereas relay of cAMP signals occurs upon perturbation of a stable steady state for parameter values close to those which produce oscillations. The developmental path suggested in the adenylate cyclase-phosphodiesterase space for the sequential transitions compares with the time course observed for the synthesis of these enzymes after starvation. It is suggested that there is general significance for the understanding of differentiation in the example given of a state-point following a developmental path in parameter space, moving from one behavioral domain to another, and thereby bringing about shifts in qualitative behavior.

3',5'-Cyclic-AMP Phosphodiesterases↗

A singular perturbation approach to diffusion reaction equations containing a point source, with application to the hemolytic plaque assay.

Many cells secrete factors which diffuse and bind to receptors on neighboring cells. These processes can be described by a nonlinear diffusion equation with a point source and spatially distributed binding reaction. We show via perturbation analysis how approximate solutions can be obtained for such equations when the binding reaction is fast compared to diffusive transport. We base our analysis on an example which is of great practical importance in immunology, the hemolytic plaque technique.

Binding Sites↗

Unified mechanism for relay and oscillation of cyclic AMP in Dictyostelium discoideum.

A modified version of an allosteric model for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] previously analyzed for sustained oscillations of adenosine 3':5'-cyclic monophosphate (cAMP) in Dictyostelium discoideum [Goldbeter, A. (1975) Nature 253, 540-542] is examined to see whether it can account for the relay of cAMP pulses. Oscillations occur around a nonequilibrium, unstable stationary state when system parameters are in a certain domain. It is found that relay can occur outside this domain, in a restricted set of parameter values for which the solution ultimately tends to a stable steady state. A suprathreshold level of extracellular cAMP is needed to elicit relay which consists in a pulsatory synthesis of intracellular cAMP. Theoretical predictions are compared with the results of experiments on cAMP relay and oscillation in aggregation-competent cells of D. discoideum. The model suggests an explanation for the emergence of aggregation centers and for a sequence of developmental events observed in interphase amoebae.

Adenylyl Cyclases↗

A simple quantitative assay for bacterial motility.

It is argued that the average motility of bacterial populations should be identified with a diffusivity parameter. A simple capillary assay for quantifying this parameter is described, and some results obtained by using this procedure are presented. It is concluded that the assay combine speed and simplicity of operation with sufficient accuracy to make it a valuable tool in the assessment of motility.

Bacterial Physiological Phenomena↗

Computer evidence concerning the chemotactic signal in Dictyostelium discoideum.

Observed pulsatile aggregation of cellular slime mould amoebae is simulated on a computer. One spatial dimension is considered. In the simulation, attractant is rapidly secreted by the cells, after a delay period, when a superthreshold attractant concentration is sensed. Cells are refractory to further signals after secretion. Once secreted, the attractant diffuses and is hydrolysed. Movement results if a cell's extending pseudopods sense a supercritical increase of attractant; if increases are sensed on both sides, a sufficiently large difference can also initiate movement. The movement continues for a period independently of further signals, but then can be reversed by a attractant increase (at the back of the cell) that surpasses a high threshold. After 100s, motion stops and the threshold for movement reverts to normal. With the above rules, and with parameter values taken, as far as possible, from the literature, the simulation provides the observed pattern of aggration. Outward moving waves of attractant and organized inward pulsatile 'steps' of cell movement surround a cell that sevretes autonomously every few minutes. Other rules fail to give this picture, or give it only for a relatively narrow range of parameter values. It appears that of the various possible signals for chemotaxos, the most likely to be used by the amoebae is a temporal increase of attractant as sensed by extending pseudopods. Nonetheless, we connot rule out the 'classical' hypothesis that cells directly sense concentration differences.

Cell Aggregation↗