Mapping Drug Physico-Chemical Features to Pathway Activity Reveals Molecular Networks Linked to Toxicity Outcome

The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either compound features (i.e., QSAR), in vitro cell based assays or molecular profiling of target tissues (i.e., expression profiling). Although these approaches have already shown the potential of predictive toxicology, we still do not have a systematic approach to model the interaction between chemical features, molecular networks and toxicity outcome. Here, we describe a computational strategy designed to address this important need. Its application to a model of renal tubular degeneration has revealed a link between physico-chemical features and signalling components controlling cell communication pathways, which in turn are differentially modulated in response to toxic chemicals. Overall, our findings are consistent with the existence of a general toxicity mechanism operating in synergy with more specific single-target based mode of actions (MOAs) and provide a general framework for the development of an integrative approach to predictive toxicology

Gardens of happiness: Sir William Temple, temperance and China

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordSir William Temple, an English statesman and humanist, wrote “Upon the Gardens of Epicurus” in 1685, taking a neo-epicurean approach to happiness and temperance. In accord with Pierre Gassendi’s epicureanism, “happiness” is characterised as freedom from disturbance and pain in mind and body, whereas “temperance” means following nature (Providence and one’s physiopsychological constitution). For Temple, cultivating fruit trees in his garden was analogous to the threefold cultivation of temperance as a virtue in the humoral body (as food), the mind (as freedom from the passions), and the bodyeconomic (as circulating goods) in order to attain happiness. A regimen that was supposed to cure the malaise of Restoration amidst a crisis of unbridled passions, this threefold cultivation of temperance underlines Temple’s reception of China and Confucianism wherein happiness and temperance are highlighted. Thus Temple’s “gardens of happiness” represent not only a reinterpretation of classical ideas, but also his dialogue with China.European CommissionLeverhulme Trus