The impact of integrating rabbit haemorrhagic disease virus (K5) release with pindone baiting on wild rabbit populations.

Several conventional and recently available tools are available for an integrated control of European rabbits in Australia. We quantified the impact of the release of rabbit haemorrhagic disease virus K5 (RHDV K5, hereafter K5) and pindone (2-pivalyl-1,3-indandione) baiting at 13 sites within Cudlee Creek fire scar in the Adelaide Hills, South Australia. K5 release was followed by pindone baiting between December 2021 and March 2022; the application of both control methods followed industry best practice. We counted rabbits using spotlights before and after the application of both control methods. Fly samples and livers from dead rabbits were collected to track K5 transmission within and between sites, and to detect the natural circulation of rabbit haemorrhagic disease virus 2 (RHDV2). K5 release had minimal impact on rabbit populations, with treated populations increasing by a mean of 65.5% at 14 days post-release and 27.9% at 77 days post-K5 release across all sites, comparable to the changes at control sites. K5 detection in flies up to 77 days post its release, and its detection in rabbit livers, demonstrates that it can survive and transmit in the environment for prolonged periods and that it can lethally infect some rabbits. This limited impact of K5 is consistent with previous studies and may be explained by pre-existing RHDV/RHDV2 immunity in the target populations or the presence of young rabbits with natural innate RHDV immunity. The detection of K5 in flies from control sites demonstrates that it was vectored beyond its release location. A reduction in rabbit counts post-pindone baiting was observed at most treatment sites, with a mean population reduction of 36.6% across all sites. Landholders need to carefully and strategically plan their integrated rabbit control programmes. Not all combinations of controls, even if theoretically logical, achieve meaningful outcomes for rabbit management.

Correction: Measurement and models accounting for cell death capture hidden variation in compound response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Measurement and models accounting for cell death capture hidden variation in compound response.

Cancer cell sensitivity or resistance is almost universally quantified through a direct or surrogate measure of cell number. However, compound responses can occur through many distinct phenotypic outcomes, including changes in cell growth, apoptosis, and non-apoptotic cell death. These outcomes have divergent effects on the tumor microenvironment, immune response, and resistance mechanisms. Here, we show that quantifying cell viability alone is insufficient to distinguish between these compound responses. Using an alternative assay and drug-response analysis amenable to high-throughput measurement, we find that compounds with identical viability outcomes can have very different effects on cell growth and death. Moreover, additive compound pairs with distinct growth/death effects can appear synergistic when only assessed by viability. Overall, these results demonstrate an approach to incorporating measurements of cell death when characterizing a pharmacologic response.

Multi-input chemical control of protein dimerization for programming graded cellular responses.

Chemical and optogenetic methods for post-translationally controlling protein function have enabled modulation and engineering of cellular functions. However, most of these methods only confer single-input, single-output control. To increase the diversity of post-translational behaviors that can be programmed, we built a system based on a single protein receiver that can integrate multiple drug inputs, including approved therapeutics. Our system translates drug inputs into diverse outputs using a suite of engineered reader proteins to provide variable dimerization states of the receiver protein. We show that our single receiver protein architecture can be used to program a variety of cellular responses, including graded and proportional dual-output control of transcription and mammalian cell signaling. We apply our tools to titrate the competing activities of the Rac and Rho GTPases to control cell morphology. Our versatile tool set will enable researchers to post-translationally program mammalian cellular processes and to engineer cell therapies.