Pattern selection in reaction diffusion systems.

Turing's theory of pattern formation has been used to describe the formation of self-organized periodic patterns in many biological, chemical, and physical systems. However, the use of such models is hindered by our inability to predict, in general, which pattern is obtained from a given set of model parameters. While much is known near the onset of the spatial instability, the mechanisms underlying pattern selection and dynamics away from onset are much less understood. Here, we provide physical insight into the dynamics of these systems. We find that peaks in a Turing pattern behave as point sinks, the dynamics of which is determined by the diffusive fluxes into them. As a result, peaks move toward a periodic steady-state configuration that minimizes the mass of the diffusive species. We also show that the preferred number of peaks at the final steady state is such that this mass is minimized. Our work presents mass minimization as a potential general principle for understanding pattern formation in reaction diffusion systems far from onset.

The control of growth and differentiation of the wing imaginal disks of Manduca sexta.

During the larval feeding period, the growth of the wing imaginal disks of Lepidoptera is dependent on continuous feeding. Feeding and nutrition exert their effect via the secretion of bombyxin, the lepidopteran insulin-like hormone. When larvae stop feeding and enter the wandering stage in preparation for metamorphosis, the control of imaginal disk growth becomes feeding and nutrition-independent. Growth of the wing imaginal disks of non-feeding wandering stage Manduca sexta can be stopped by removal of the brain, indicating that a brain-derived factor is required for continued disk growth. Isolated wing disk growth in vitro requires both 20-hydroxyecdysone (20E) and either brain extract or bombyxin to achieve normal growth. In vitro, brain extracts and synthetic bombyxin have little or no effect in stimulating disk growth, but they greatly enhance the effect of 20E, indicating that 20E and bombyxin act synergistically to modulate growth of the imaginal disk. Brain extract and bombyxin induce a suite of insulin-response events in cultured wing disks, which indicate that bombyxin and 20E act through separate and synergistic pathways. The dose-response to 20E reaches a plateau at about 0.1 microg/ml. Tracheal differentiation of the wing disks can be induced to initiate in vitro by a low concentration of 20E, whereas higher concentrations of 20E only stimulate growth.

Corticotropin-releasing hormone deficiency increases allergen-induced airway inflammation in a mouse model of asthma.

BACKGROUND: Corticotropin-releasing hormone (CRH) is a major regulator of adrenocorticotropic hormone and the production of glucocorticoids by the adrenal gland. Abnormal regulation of CRH and endogenous glucocorticoids has been implicated in the pathogenesis of asthma. OBJECTIVE: We postulated that CRH deficiency could increase asthma severity by disrupting hypothalamus-pituitary-adrenal axis function and the induction of glucocorticoids through inflammatory and physiologic stress. However, CRH is expressed by several types of immune cells and might be induced at sites of inflammation, where it has local immunostimulatory actions. Thus CRH deficiency could decrease asthma severity. METHODS: To test these possibilities, we subjected CRH-knockout mice to an ovalbumin-induced airway inflammation protocol that mimics many features of asthma. RESULTS: CRH-knockout mice had an increase in airway inflammation of approximately 80% to 300% and an increase in goblet cell hyperplasia of approximately 70% compared with wild-type mice. In contrast, IgE induction was unaffected by CRH deficiency. The increased inflammation in knockout mice was associated with increased tissue resistance, elastance, and hysteresivity. Levels of IL-4, IL-5, IL-13, RANTES, IFN-gamma, and eotaxin were all increased in knockout mice. Serum corticosterone levels were decreased in knockout mice and might account for some of the differences between knockout and wild-type mice. CONCLUSION: We conclude that CRH deficiency disrupts endogenous glucocorticoid production and enhances allergen-induced airway inflammation and lung mechanical dysfunction in mice. Thus inherited or acquired CRH deficiency could increase asthma severity in human subjects.