Dick, N. | bioRxiv Science

bioRxiv2023

High-density sampling reveals volume growth in human tumours

In growing cell populations such tumours, mutations can serve as markers that allow tracking the past evolution from current samples. The genomic analyses of bulk samples and samples from multiple regions have shed light on the evolutionary forces acting on tumours. However, little is known empirically on the spatio-temporal dynamics of tumour evolution. Here, we leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grow predominantly uniformly within the tumour volume instead of at the surface. We determine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. Our methods shed light on the early evolution of tumours in vivo and can be applied to high-resolution data in the emerging field of spatial biology.

cancer biology↗

bioRxiv2023

Pesticide-induced resurgence of the brown planthopper is mediated by diverse actors that promote juvenile hormone biosynthesis and female fecundity

Pesticide-induced resurgence, increases in pest insect populations following pesticide application, is a serious threat to the sustainable control of many highly damaging crop pests. Resurgence can result from pesticide-enhanced pest reproduction, however, the molecular mechanisms mediating this process remain unresolved. Here we show that brown planthopper (BPH) resurgence in rice crops following exposure to sublethal doses of the pesticide emamectin benzoate (EB) results from the coordinated action of a suite of genes that regulate juvenile hormone (JH) levels, resulting in increased JH titer in adult females and enhanced fecundity. We demonstrate that EB treatment at sublethal levels results in profound changes in female BPH fitness including increased egg maturation and oviposition. This enhanced reproductive fitness results from the EB-mediated upregulation of key genes involved in the regulation of JH, including JHAMT and Kr-h1 and the downregulation of allatostatin (AstA) and allatostatin receptor (AstAR) expression. AstA signaling is known to inhibit the production of JH in the corpora allata and hence EB exposure diminishes this inhibitory action. We find that the changes in gene expression following EB exposure are caused by the allosteric action of this insecticide on its molecular target, the glutamate-gated chloride channel (GluCl). Collectively, these results provide mechanistic insights into the regulation of negative pesticide-induced responses in insects and reveal some key actors involved in the JH-signaling pathway that underpin pesticide resurgence. SignificancePesticides remain a key means of controlling many of the worlds insect pests. However, in some cases, pesticide applications can result in resurgence of pest populations due to pesticide-induced increases in fecundity. In the current study, we show that pesticide resurgence in the brown planthopper (BPH) following exposure to the insecticide emamectin benzoate (EB) results from the transcriptional reprogramming of a diverse suite of positive and negative regulators of juvenile hormone (JH), a critical regulator of insect development and reproduction. This in turn leads to profound increases in female BPH reproductive fitness and enhanced fecundity. Our findings unravel some of the molecular mechanisms mediating pesticide-induced pest resurgence and inform the development of novel strategies to control highly damaging crop pests.

ecology↗