Chris Oldfield

This special issue explores both the metaphysical and theological significance of “middle-sized things” — everyday objects, persons, and sacraments — in light of developments in contemporary science and philosophy. Against prevailing neo-Humean and microphysicalist backdrops, where only microphysical entities are taken as fundamental, contributors interrogate the ontological reality and causal powers of the macroscopic domain through engagements with quantum physics, biology, the metaphysics of substance, and sacramental theology. Essays range from arguments for Aristotelian hylomorphism and critiques of reductionism to narrative theories of identity and teleological accounts of divine action. Together, they examine whether middle-sized entities can be causally efficacious, metaphysically basic, and theologically significant.

Protein–protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein–protein recognition mechanism, mediated by disordered regions longer than 20–30 residues. Bioinformatics predictions and well‐characterized examples, such as the kinase‐inhibitory domain of Cdk inhibitors and the Wiskott–Aldrich syndrome protein (WASP)‐homology domain 2 of actin‐binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.