Hancock, G. R. | bioRxiv Science

bioRxiv2025

The effects of habitat structure and lighting on object and background appearance

The color, geometry, and lighting of environments characterize their appearance to humans and other animals and, as a result, play an important role in the evolution of animal coloration. Yet despite this long-standing association, how changes in lighting from atmospheric conditions and three-dimensional geometry interact to alter the appearance of scenes and animals remains largely unexplored. To investigate these interactions, we quantified the appearance of natural backgrounds and standardized targets with color-calibrated photographs and 3-dimensional (3D) scans of 672 natural scenes taken under diffuse and direct lighting conditions. We find several instances where lighting and the local 3D environment systematically altered the colors and patterns of scenes and a target object, as well as their relationship with spatial scale. Shadows formed under direct lighting increased luminance and short-long wave (blue-yellow) contrast across spatial scales, especially at larger spatial scales for habitats with a greater 3D variation. Conversely, medium-long wave (green-red) information was highly stable to changes in lighting. Direct lighting and the 3D environment also influenced the directionality and orientation of patterns within the scenes and targets due to the formation of cast and self-shadows of different orientations. These analyses demonstrate the importance of considering the lighting and geometry of an environment when comparing the statistics of animals and their backgrounds.

ecology↗

bioRxiv2024

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ER) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ER ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ER breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29s activities in breast cancer cells harboring Y537S ER. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

cancer biology↗