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D M Holloway

Publications and source records attributed to D M Holloway.

6 recordsLinked to original sources

Time-resolved phosphorescence of tyrosine, tyrosine analogs, and tyrosyl residues in oxytocin and small peptides.

We present the time-resolved phosphorescence of oxytocin, two oxytocin derivatives, vasopressin and a series of compounds that serve as models for free tyrosine. One of the oxytocin derivatives, desaminodicarbaoxytocin, has the disulfide bridge replaced by an ethylene bridge, and lacks the N-terminus. Similar to the reported fluorescence decays of tyrosine in these peptides, the phosphorescence decays generally are not single exponentials, but can be fit as biexponentials. The decay times for the oxytocin peptides are shorter than for desaminodicarbaoxytocin or the model compounds, and this we attribute to enhanced spin-orbit coupling due to the presence of sulfur. We measured the phosphorescence decay of the model cyclic pentapeptide that contains tyrosine and compared it to that observed for the same cyclic pentapeptide in which tyrosine is replaced by tryptophan. We also report the phosphorescence of 2-tryptophan-oxytocin, and deamino-2-tryptophan-oxytocin in which biexponential phosphorescence decay is also observed.

Disulfides↗

Complex morphogenesis of surfaces: theory and experiment on coupling of reaction-diffusion patterning to growth.

Reaction-diffusion theory for pattern formation is considered in relation to processes of biological development in which there is continuous growth and shape change as each new pattern forms. This is particularly common in the plant kingdom, for both unicellular and multicellular organisms. In addition to the feedbacks in the chemical dynamics, there is then another loop linking size and shape changes with the reaction-diffusion patterning of growth controllers in the growing region. In studies by computation, the codes must incorporate, alongside the usual solvers of the partial differential dynamic equations, a versatile growth code, to express any kind of shape change. We have found that regulation of shape change in particular ways (e.g. to make narrow-angle branchings) demands new features in our chemical mechanisms. Our growth algorithm is for a surface growing tangentially, but moving outward and changing shape to accommodate the extra area. This is potentially applicable both to the tunica layer of multicellular plant meristems and to the growing tip of the cell surface, e.g. in the morphogenesis of single-celled chlorophyte algae which display branching processes: whorl formation in Acetabularia (Dasycladales) and repeated dichotomous branching in Micrasterias (Desmidiaceae). For computational studies, a hemispherical shell is a reasonable idealization of the initial shape. We describe results of two types of study: (1) Pattern formation by three reaction-diffusion models, with contrasted nonlinearities, on the hemispherical shell, particularly to find conditions for robust formation of annular pattern or pattern for dichotomous branching, both of which are common in plants. (2) Sequential dichotomous branchings in a system growing and changing in shape from the hemispherical start.

Journal Article↗

Suppression of positional errors in biological development.

Cells in developing embryos behave according to their positions in the organism, and therefore seem to be receiving 'positional information'. A widespread view of the mechanism for this is that each cell responds locally to the concentration level of some extracellular chemical which is distributed in a spatial gradient. For molecules conveying and receiving the positional signal, concentrations are likely to be low enough that, per individual cell, only a few thousand molecules may be involved. Fluctuations to be expected in these numbers (Poisson distribution) could readily lead to errors up to a few percent of embryo length in the reading of position. This is an intolerable level of error for some developmental pattern-forming events. Embryos must have means of suppressing such errors. We maintain that this requires communication between cells, and illustrate this by using the reaction part of two well-known Turing-type reaction-diffusion models as the local gradient reader. We show that switching on diffusion in these models leads to adequate suppression of positional errors.

Animals↗

Computations of post-inductive dynamics in axolotl heart formation.

This paper reports modelling of heart localization in the axolotl (Ambystoma mexicanum). The region of heart specification in the mesoderm defined by classical induction from the endoderm is larger than the area of final myocardial differentiation. For localizing the area of differentiation within the area of specification, we postulate a reaction-diffusion system that arises within the mesoderm in response to induction from the endoderm. This mechanism generates a spatial pattern for two chemicals, an activator and an inhibitor, corresponding to the area of myocardial differentiation. We postulate a diffusible chemical rescuer, which is absent in the cardiac lethal mutant, and which is a precursor to the reaction-diffusion mechanism. The activator, inhibitor, rescuer, and product of endodermal induction are presented in an enzyme mechanism with rate equations similar to the Gierer-Meinhardt equations. These equations were solved numerically in both one and two spatial dimensions. We have attained quantitative agreement with the experimental data for sizes of tissue regions and for times to heartbeat. Experiments modelled include wild-type heart localization as well as both in vitro and in vivo rescue of cardiac lethal mesoderm with wild-type mesoderm. Based upon the parameters necessary to model heart localization, we make a series of predictions. We predict: a specific profile for the endodermal inducer gradient; the possibility of producing multiple hearts in vivo; and a greater contribution to the heart from the wild-type mesoderm for in vivo transplants with cardiac lethal mesoderm. We make some suggestions as to the possible chemical nature of the substances in the model. We indicate that the inhibitory field and mechanochemical theories are probably not as promising as reaction-diffusion for the mechanism of heart localization.

Ambystoma mexicanum↗