Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two‐step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non‐sleeping systems can be made insensitive (...) (or hypersensitive) to some anesthetics by modifying a single pre‐synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep. (shrink)

Leibniz claimed that the universe, if God-created, would be physically and morally optimal in this conjoint sense: Of all possible worlds, it would be richest in phenomena, but its richness would arise from the simplest physical laws and conditions. This claim raises two difficult questions. First, why would this “richest/simplest” world be morally optimal? Second, what is the optimal balance between these competing criteria? The latter question is especially hard to answer in the context of a multiverse or multi-domain universe. (...) Leibniz focused on goodness as God’s motive in creation. “This is the cause of the existence of the best: that his wisdom makes it known to God, his goodness makes him choose it, and his power lets him produce it.” This article suggests that love is God’s motive. Since love entails acting to both benefit and be with the beloved, limitless love would entail God’s becoming as much unified reality as possible. The physical laws that govern the universe and its vast richness of phenomena appear to be those that we should expect if this claim is true and there are ways of testing the closeness of this fit. The claim that God has become the world (pandeism) also offers a satisfying resolution to the problem of evil. (shrink)