Multiscale metabolic modeling of C4 plants: connecting nonlinear genome-scale models to leaf-scale metabolism in developing maize leaves

C4 plants, such as maize, concentrate carbon dioxide in a specialized compartment surrounding the veins of their leaves to improve the efficiency of carbon dioxide assimilation. Nonlinear relationships between carbon dioxide and oxygen levels and reaction rates are key to their physiology but cannot be handled with standard techniques of constraint-based metabolic modeling. We demonstrate that incorporating these relationships as constraints on reaction rates and solving the resulting nonlinear optimization problem yields realistic predictions of the response of C4 systems to environmental and biochemical perturbations. Using a new genome-scale reconstruction of maize metabolism, we build an 18000-reaction, nonlinearly constrained model describing mesophyll and bundle sheath cells in 15 segments of the developing maize leaf, interacting via metabolite exchange, and use RNA-seq and enzyme activity measurements to predict spatial variation in metabolic state by a novel method that optimizes correlation between fluxes and expression data. Though such correlations are known to be weak in general, here the predicted fluxes achieve high correlation with the data, successfully capture the experimentally observed base-to-tip transition between carbon-importing tissue and carbon-exporting tissue, and include a nonzero growth rate, in contrast to prior results from similar methods in other systems. We suggest that developmental gradients may be particularly suited to the inference of metabolic fluxes from expression data.Comment: 57 pages, 14 figures; submitted to PLoS Computational Biology; source code available at http://github.com/ebogart/fluxtools and http://github.com/ebogart/multiscale_c4_sourc

Prolegomena to Any Future Historicizing: The Dilthey-Husserl Debate and Why It Matters for Critical Phenomenology

For more than a century, phenomenology’s relation to history has remained a problem for phenomenological analysis. This can in part be attributed to the circumstances surrounding the beginnings of phenomenology. As Europe moved increasingly toward world war at the turn of the 20th century, a growing consciousness of the historical relativity of all values and knowledge spread throughout the continent, leading Ernst Troeltsch to speak of the “crisis of historicism” (Rand 1964, 504-5). In this same context, Edmund Husserl framed phenomenological analysis in opposition to history. While Husserl recognized the “tremendous value” that history has to offer philosophical thinking, he believed that a purely historical reduction of consciousness necessarily results in the relativity of historical understanding itself, like a serpent that bites its own tail (Husserl 2002, 280). If phenomenology was to be a genuine science, it had to attempt a phenomenological reduction which would seize upon the essence of our historical being, i.e., our essence as beings that exist within history and are inseparable from it. What was required over and beyond a historical understanding of lived experience was an analysis of the structure of historicity itself (293-4). Peer review process: Guest edite