A New History for Human Rights: Conflict of Laws as Adjacent Possibility

The pivotal contributions of private international law to the conceptual emergence of international human rights law have been largely ignored. Using the idea of adjacent possibility as a theoretical metaphor, this article shows that conflict of laws analysis and technique enabled the articulation of human rights universalism. The nineteenth-century epistemic practice of private international law was a key arena where the claims of individuals were incrementally cast as being spatially independent from their state of nationality before rights universalism became mainstream. Conflict of laws was thus a vital combinatorial ingredient contributing to the dislocation of rights from territory that underwrites international human rights today

Nat Metab.

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3,4,5,6,7,8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system.Développment d'une infrastructure française distribuée coordonnéeLa signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métaboliqueInnovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeu