Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design

Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids.

L1 Acquisition of interface properties across Portuguese dialects: modular and interdisciplinary interfaces as sources of explanation

This study investigates the child (L1) acquisition of properties at the interfaces of morphosyntax, syntax-semantics and syntax-pragmatics, by focusing on inflected infinitives in European Portuguese (EP). Three child groups were tested, 6–7-year-olds, 9–10-year-olds and 11–12-year-olds, as well as an adult control group. The data demonstrate that children as young as 6 have knowledge of the morpho-syntactic properties of inflected infinitives, although they seem at first glance to show partially insufficient knowledge of their syntax–semantic interface properties (i.e. non-obligatory control properties), differently from children aged 9 and older, who show clearer evidence of knowledge of both types of properties. However, in general, both morpho-syntactic and syntax–semantics interface properties are also accessible to 6–7-year-old children, although these children give preference to a range of interpretations partially different from the adults; in certain cases, they may not appeal to certain pragmatic inferences that permit additional interpretations to adults and older children. Crucially, our data demonstrate that EP children master the two types of properties of inflected infinitives years before Brazilian Portuguese children do (Pires and Rothman, 2009a,b), reasons for and implications of which we discuss in detail.

Interfaces in the acquisition of syntax

We introduce empirical work on Romance language acquisition with respect to the interfaces of syntax with other modules of grammar (internal interfaces) and other domains of cognition (external interfaces). We do so by choosing specific phenomena within the following interfaces: syntax-morphology, syntax-semantics and syn-tax-pragmatics. In the domain of syntax-morphology we focus on grammatical gender, with respect to the syntax-semantics interface we focus on adjectival placement (pre- and post-nominal) and with regard to the syntax-discourse/pragmatics interface we review work on the null/overt subject distribution. Finally, we summarize research on articles, suggesting that articles represent a multiple interface. We provide examples from different types of learners and across the four major Romance languages French, Italian, Portuguese and Spanish. While our central goal is to summarize and generalize across major findings, we will also point to potential problems concerning the interface approach, e.g. the association of particular phenomena with a specific interface and the assumption that internal interfaces are less problematic than external ones.