Dixon, V. | bioRxiv Science

bioRxiv2025

From form to function: Morphology as a proxy for life history and population performance in fish

O_LILife history strategies emerge from trade-offs between growth, survival and reproduction and are key predictors of how populations respond to environmental disturbances. However, estimating these strategies typically requires detailed demographic data, which are unavailable for many species. Because morphological traits govern whole-organism performance, selection on ecological performance can link morphology with life history strategies. Morphological traits can thus be practical proxies for life history strategies, offering a scalable approach for data-deficient populations. C_LIO_LITo test the hypothesis that morphological traits predict major life-history axes via shared performance trade-offs, we parameterised dynamic energy budget integral projection models for 290 marine and freshwater fish species to quantify life history strategies and measured eight morphological traits from lateral-view photographs for each species. We used phylogenetically corrected principal component analysis to summarise life history strategies and morphological traits, and tested whether morphology predicts life history strategies. C_LIO_LILateral size morphology, comprising body elongation, relative eye size and oral gape position predicted generation turnover depending on water column position, and predicted reproductive output depending on clade. C_LIO_LIOur results support the hypothesis that morphologies linked to ecological performance scale up to shape demographic strategies, providing proof of concept that morphology can predict life-history strategies. They also highlight the potential to develop performance-based trait proxies for rapid, low-cost estimations of demographic vulnerability and recovery potential across data-poor fish populations--expanding the scope of life-history frameworks for fisheries management and conservation under increasing pressures from overfishing, habitat loss and climate change. C_LI

ecology↗

bioRxiv2022

Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

BackgroundMuscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies or anti-FGFR treatments, these tumors are still of poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating molecular heterogeneity of MIBC and UTUC, to facilitate preclinical identification of therapies. MethodsFresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays) and genomic profiles (targeted-NGS). Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies (FGFR and EGFR inhibitors). Results31 PDXs were established from 1 non-MIBC, 25 MIBC, 5 upper urinary tract tumors, including 28 urothelial (UCC) and 3 squamous-cell carcinomas (SCC). Integrated genomic and transcriptomic profiling identified PDXs of 3 different consensus molecular subtypes (Basal/Squamous, Luminal papillary and Luminal unstable), and included FGFR3-mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a basal/squamous patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy and we did not observe association between subtypes and response. Of the 3 basal/squamous models treated with anti-EGFR therapy, two models were sensitive and one model, of sarcomatoid variant, was resistant. Treatment of 3 FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone. ConclusionsWe developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. Pharmacological characterization of the PDXs suggested that upper urinary tract and MIBCs, UCC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.

cancer biology↗