Down a rabbit hole: burrowing behaviour and larger home ranges are related to larger brains in leporids

Studies on the evolution of brain size variation usually focus on large clades encompassing broad phylogenetic groups. This risks introducing ‘noise’ in the results, often obscuring effects that might be detected in less inclusive clades. Here, we focus on a sample of endocranial volumes (endocasts) of 18 species of rabbits and hares (Lagomorpha: Leporidae), which are a discrete radiation of mammals with a suitably large range of body sizes. Using 60 individuals, we test five popular hypotheses on brain size and olfactory bulb evolution in mammals. We also address the pervasive issue of missing data, using multiple phylogenetic imputations as to conserve the full sample size for all analyses. Our analyses show that home range and burrowing behaviour are the only predictors of leporid brain size variation. Litter size, which is one of the most widely reported constraints on brain size, was unexpectedly not associated with brain size. However, a constraining effect may be masked by a strong association of litter size with temperature seasonality, warranting further study. Lastly, we show that unreasonable estimations of phylogenetic signal (Pagel’s lamba) warrant additional caution when using small sample sizes, such as ours, in comparative studies

Anti-CTLA-4 therapy requires an Fc domain for efficacy

Item does not contain fulltextIpilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcgamma receptor (FcgammaR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4 and its ligand by occluding the ligand-binding motif on CTLA-4 as shown crystallographically. We used H11 to visualize CTLA-4 expression in vivo using whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4 blockade has minimal effects on antitumor responses. Installation of the murine IgG2a constant region on H11 dramatically enhances its antitumor response. Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding antibodies require an Fc domain for antitumor effect