Biology subjects

Black, J. R.

Publications and source records attributed to Black, J. R..

5 recordsLinked to original sources

bioRxiv2026

Optimising neural contrast and minimising tissue shrinkage in dragon lizard brains: buffered Lugol's iodine versus phosphotungstic acid for contrast-enhanced μCT

Contrast-enhanced micro-computed tomography (CT) has become a valuable tool for addressing neuroanatomical questions that previously required destructive histology. As a relatively new technique, it remains subject to ongoing technical refinement, and taxon- and tissue-specific protocol optimisation. We evaluated the performance of two common contrast-enhancing agents, buffered Lugol's iodine and phosphotungstic acid (PTA) in aqueous solution, for CT visualisation of the nervous system in the Jacky dragon lizard, Amphibolurus muricatus by comparing staining time, contrast specificity and brain tissue shrinkage evaluated at three concentrations (1.25%, 2.5% and 5%). Buffered Lugol's iodine outperformed aqueous PTA by requiring shorter staining times (as short as four days) and providing better white matter-grey matter differentiation, whereas PTA required longer incubation periods of approximately three weeks and produced poorer white-grey matter differentiation. Importantly, buffered Lugol's iodine produced higher brain-to-endocast occupancy estimates than aqueous PTA, suggesting substantially reduced tissue shrinkage. PTA-treated specimens exhibited an estimated 13.3% reduction in occupancy and approximately 20% greater brain tissue shrinkage than buffered Lugol's-treated specimens. Together, these findings demonstrate that buffered Lugol's iodine staining provides the high level of internal tissue contrast required to resolve fine-scale neuroanatomical organisation in three dimensions, preserves the spatial relationships among anatomical structures, and reduces artefacts, all of which result in a closer correspondence between the brain and endocranial cavity. From a practical perspective, the study provides guidance for contrast agent selection in future CT studies and reveals that buffered Lugol's iodine is better suited to fine-scale neuroanatomical, volumetric and geometric morphometric analyses, whereas PTA is advantageous for applications prioritising general soft-tissue or musculoskeletal visualisation.

neuroscience↗

bioRxiv2026

Quantifying evolutionary novelty and design efficiency in generative genome design

Generative genome design models can now produce previously unobserved genome-length sequences, but assessing their capabilities is complicated by limitations in functional prediction. The ability to engineer genomes faster than we can understand them risks creating biosecurity vulnerabilities. To evaluate these potential risks systematically, we propose a framework that distinguishes between (i) evolutionary novelty, quantified through phylogenetic and sequence similarity to natural genomes; and (ii) design efficiency - the efficiency with which a model finds viable sequences compared to simple baseline generators. Applying this framework to bacteriophages designed by the genome language model Evo 2, we find that model likelihood strongly predicts experimental viability, capturing functional constraints beyond simple biological heuristics. However, this efficiency derives largely from staying close to previously observed sequences rather than exploring novel sequence space, reflecting the combined performance of the model and additional filters that were applied to its outputs. Compared to baselines of random mutagenesis and serial passage, the model achieves substantial design efficiency while its outputs remain phylogenetically close to natural genomes. We conclude that the generative capabilities of Evo 2 warrant low to moderate biosecurity concern for de novo hazard creation, although the degree to which these findings generalise to larger or less constrained viral architectures is an open question. Our framework enables an evidence-based capability assessment of generative genome design tools, informing future biosecurity evaluations.

genomics↗

bioRxiv2026

YAP disrupts bile acid homeostasis to drive cancer-associated cachexia

Cancer-associated cachexia is a severe metabolic syndrome marked by dramatic loss of adipose and muscle mass. Although preclinical models have advanced our understanding of cachexia, there are still no approved therapies due to the limited insights into the mechanisms underlying tissue wasting. Here, we utilise a YAP-driven model of liver cancer in zebrafish, which rapidly develops cachexia, to uncover an evolutionarily conserved role for bile acid disruption in the onset of cachexia. Spatial transcriptomic analysis revealed that YAP induces a bi-lineage cholangiocarcinoma phenotype, which was associated with bile acid dysregulation. Mechanistically, we establish that both bile acid synthesis (via CYP7A1) and signalling through the bile acid receptor TGR5 are essential for cachexia induction. Notably, we find that the promotion of bile acid excretion with odevixibat ameliorates cachexia. Together, our findings reveal an evolutionarily conserved mechanism by which YAP promotes cachexia and suggest a potential therapeutic strategy to treat the syndrome.

cancer biology↗

bioRxiv2025

Agent-based simulations of lung tumour evolution suggest that ongoing cell competition drives realistic clonal expansions

Computational simulations of tumour evolution are increasingly used to infer the rules underlying cancer growth, with the goal of one day recommending tailored treatments. To make reliable inferences, such models must be able to reflect the properties of real tumours. Recent work has shown that lung tumours undergo frequent and late subclonal expansions, which are associated with poor prognosis. This paper tests three candidate simulations of three-dimensional tumour growth, which make different assumptions about the nature of competition between cells, for their ability to replicate these late expansions. Only a model which assumes stringent competition between tumour cells for existing tissue space, after the tumour has reached a fixed size, can produce multiregion sequencing data realistic to lung tumours. This work also assesses the influence of these assumptions on the inferred selection strength of individual tumours in a large cohort of lung cancers, and finds that inferences from a well-tailored model produce much higher estimates than poorly-tailored models of the effects of driver mutations on cell fitness. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/686578v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@40fae9org.highwire.dtl.DTLVardef@18f2d2org.highwire.dtl.DTLVardef@1edec55org.highwire.dtl.DTLVardef@136d1da_HPS_FORMAT_FIGEXP M_FIG Computational simulations of tumour evolution are increasingly used to infer the rules underlying cancer growth, with the goal of one day recommending tailored treatments. Here we show that the properties of lung cancer sequencing data are best replicated by a model which assumes that cells compete both to proliferate and survive. C_FIG

cancer biology↗

bioRxiv2020

High throughput micro-CT scanning of small fossils: preparation, packing, parameters and post-processing

High-resolution X-ray microcomputed tomography, or microCT (CT), enables the digital imaging of whole objects in three dimensions. The power of CT to visualise internal features without disarticulation makes it particularly valuable for the study of museum collections, which house millions of physical specimens documenting the spatio-temporal patterns of life. Despite its potential for comparative analyses, most CT studies include limited numbers of museum specimens, due to the challenges of digitising numerous individuals within a project scope. Here we describe a method for high-throughput CT scanning of hundreds of small (< 2 cm) specimens in a single container, followed by individual labelling and archival storage. We also explore the effects of various packing materials and multiple specimens per capsule to minimize sample movement that can degrade image quality, and hence CT investment. We demonstrate this protocol on vertebrate fossils from Queensland Museum, Australia, as part of an effort to track community responses to climate change over evolutionary time. This system can be easily modified for other types of wet and dry material amenable to X-ray attenuation, including geological, botanical and zoological samples, providing greater access to large-scale phenotypic data and adding value to global collections.

evolutionary biology↗