All's well that begins Wells: Celebrating 60 years of Animal Behaviour and 36 years of research on anuran social behaviour

The scientific study of frogs and toads as important systems in behavioural ecology traces its roots to an influential review published in this journal 36 years ago (Wells 1977a, ‘The social behaviour of anuran amphibians’, Animal Behaviour, 25, 666–693). In just 28 pages, Wells summarized the state of knowledge on important behaviours associated with anuran breeding and introduced an evolutionary framework ‘for understanding the relationship between social behaviour and ecology’ (page 666) that was largely lacking in earlier treatments of this group. Not only is Wells's review one of the most cited papers ever published in Animal Behaviour, it is also responsible for setting broad research agendas and shaping much of our current thinking on social behaviour in an entire order of vertebrates. As such, it is entirely appropriate that we honour Wells's review and its contributions to the study of animal behaviour in this inaugural essay celebrating 12 papers selected by the community as the most influential papers published in the 60-year history of Animal Behaviour. In our essay, we place Wells's review in historical context at the dawn of behavioural ecology, highlight the field's progress in answering some major research questions outlined in the review, and provide our own prospectus for future research on the social behaviour of anuran amphibians. Highlights ► This essay celebrates Kent Wells's (1977, Animal Behaviour, 25, 666–693) paper, ‘The social behaviour of anuran amphibians’. ► We place the article in historical context and outline its major contributions. ► We discuss progress on anuran social behaviour since its publication in 1977. ► We provide our own prospectus on the future of anuran behavioural ecology

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Knockout and transgenic studies in mice demonstrate that normal somatic tissues redundantly express 3 cyclin D proteins, whereas tumor cells seem dependent on a single overexpressed cyclin D. Thus, selective suppression of the individual cyclin D deregulated in a tumor represents a biologically valid approach to targeted cancer therapy. In multiple myeloma, overexpression of 1 of the cyclin D proteins is a ubiquitous feature, unifying at least 7 different initiating genetic events. We demonstrate here that RNAi of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. By screening a chemical library using a cell-based assay for inhibition of CCND2 trans-activation, we identified the plant cytokinin kinetin riboside as an inhibitor of CCND2 trans-activation. Kinetin riboside induced marked suppression of CCND2 transcription and rapidly suppressed cyclin D1 and D2 protein expression in primary myeloma cells and tumor lines, causing cell-cycle arrest, tumor cell–selective apoptosis, and inhibition of myeloma growth in xenografted mice. Mechanistically, kinetin riboside upregulated expression of transcription repressor isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by various myeloma oncogenes and cis-activation of translocated CCND1, suggesting induction of an overriding repressor activity that blocks multiple oncogenic pathways targeting cyclin D genes. These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies