An adaptable in silico ensemble model of the arachidonic acid cascade.

Eicosanoids are a family of bioactive lipids, including derivatives of the ubiquitous fatty acid arachidonic acid (AA). The intimate involvement of eicosanoids in inflammation motivates the development of predictive in silico models for a systems-level exploration of disease mechanisms, drug development and replacement of animal models. Using an ensemble modelling strategy, we developed a computational model of the AA cascade. This approach allows the visualisation of plausible and thermodynamically feasible predictions, overcoming the limitations of fixed-parameter modelling. A quality scoring method was developed to quantify the accuracy of ensemble predictions relative to experimental data, measuring the overall uncertainty of the process. Monte Carlo ensemble modelling was used to quantify the prediction confidence levels. Model applicability was demonstrated using mass spectrometry mediator lipidomics to measure eicosanoids produced by HaCaT epidermal keratinocytes and 46BR.1N dermal fibroblasts, treated with stimuli (calcium ionophore A23187), (ultraviolet radiation, adenosine triphosphate) and a cyclooxygenase inhibitor (indomethacin). Experimentation and predictions were in good qualitative agreement, demonstrating the ability of the model to be adapted to cell types exhibiting differences in AA release and enzyme concentration profiles. The quantitative agreement between experimental and predicted outputs could be improved by expanding network topology to include additional reactions. Overall, our approach generated an adaptable, tuneable ensemble model of the AA cascade that can be tailored to represent different cell types and demonstrated that the integration of in silico and in vitro methods can facilitate a greater understanding of complex biological networks such as the AA cascade.

Specialist Herbivore Performance on Introduced Plants During Native Host Decline.

Ash (Fraxinus spp.) is in rapid decline across the northeastern USA due to the invasive emerald ash borer (Agrilus planipennis Fairmaire). Three recently co-occurring confamilial species may serve as alternative larval host plants for ash-reliant Lepidoptera. These prospective hosts are nonnative shrubs often planted in managed suburban landscapes and are sometimes invasive or naturalized in North America. Given the imminent decline of ash trees, we considered potential downstream effects on insect herbivores historically specialized on ash foliage. We measured the performance of three ash-specialist hawkmoths (Lepidoptera: Sphingidae) on native white ash (Fraxinus americana L.) and alternative host plants: common lilac (Syringa vulgaris L.), weeping forsythia [Forsythia suspensa (Thunb.) Vahl], and European privet (Ligustrum vulgare L.). We found the nonnative host plants provided varied support for larval survival to pupation, with biomass and growth rate affected differently by both plant and insect identity. Nearly all caterpillars reared on one alternative host, European privet, exhibited distinct malformations of the wing buds at pupation. Given caterpillar presence on privet in the field, privet may constitute an ecological trap (i.e., when female moths select a sub-optimal host, offspring survival and fitness are reduced). This work demonstrates how performance testing can reveal species-specific effects of host plant loss on mono- or oligophagous insects. For some ash specialists, alternative nonnative host plants may be suboptimal, but some cultivated host plants may be able to support certain specialist insects during native host decline. We suggest that landscaping decisions can be tailored to support threatened insect species.