Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.     

Gould, Hull, and the Individuation of Scientific Theories

When is conceptual change so significant that we should talk about a new theory, not a new version of the same theory? We address this problem here, starting from Gould’s discussion of the individuation of the Darwinian theory. He locates his position between two extremes: ‘minimalist’—a theory should be individuated merely by its insertion in a historical lineage—and ‘maximalist’—exhaustive lists of necessary and sufficient conditions are required for individuation. He imputes the minimalist position to Hull and attempts a reductio: this position leads us to give the same ‘name’ to contradictory theories. Gould’s ‘structuralist’ position requires both ‘conceptual continuity’ and descent for individuation. Hull’s attempt to assimilate into his general selectionist framework Kuhn’s notion of ‘exemplar’ and the ‘semantic’ view of the structure of scientific theories can be used to counter Gould’s reductio, and also to integrate structuralist and population thinking about conceptual change.     

Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.