Biology subjects

Page, G.

Publications and source records attributed to Page, G..

3 recordsLinked to original sources

bioRxiv2025

Enhancing cryopreservation of ex vivo 3D tumor models using vitrification strategies

Microdissected tumor tissue explants (MDTs) are promising ex vivo models for oncology research but remain limited by poor preservation and the rapid loss of viability following resection. Here, we systematically optimized MDT cryopreservation using prostate-derived 49F and ovarian TOV112D tumor models. Before cryopreservation, we evaluated the effects of antioxidant supplementation, pre-cooling, and a short recovery period. MDTs were then preserved by either conventional slow-freezing or vitrification using ultra-rapid cooling. Following thawing, tissue morphology, apoptosis, and proliferative capacity were assessed relative to fresh controls. Vitrification improved morphological preservation and reduced apoptosis compared with slow-freezing, although recovery of proliferation differed between tumor models. Antioxidant supplementation enhanced post-thaw proliferation at optimal concentrations but induced toxicity at higher doses. Pre-cooling and a short pre-cryopreservation recovery period further improved post-thaw outcomes. Combining these parameters produced an optimized vitrification protocol that preserved up to 98% of the proliferative capacity of 49F MDTs and 69% of that of TOV112D MDTs relative to fresh controls. These findings establish optimized vitrification as a reproducible, high-yield strategy for preserving MDTs for downstream ex vivo oncology applications.

cancer biology↗

bioRxiv2025

Problem-solving without a cortex: inferior lobe drives goal-directed object manipulation in cichlid fish

Goal-directed object manipulation and problem-solving, which are necessary to evolve tool use behaviors, have long been linked to the expansion of the telencephalon in mammals and birds. Here, we show that goal-directed object manipulation in cichlid fish is driven by a non-telencephalic brain structure, the inferior lobe. Using manganese-enhanced MRI (MEMRI) on an ultra-high field 17.2 Tesla MRI system, we show that the inferior lobe is activated during a puzzle-box opening task. Furthermore, magnetic resonance (MR)-guided High Intensity Focused Ultrasound (HIFU) lesions profoundly impair fine motor coordination during this task without affecting general locomotion or motivation. These results reveal that cortex-like cognitive functions can arise from non-telencephalic brain structures in teleosts. With no homolog in tetrapods, the inferior lobe is a critical hub for flexible behavior in teleost fish. Our findings highlight the existence of alternative neural architectures for the emergence of complex cognition.

neuroscience↗

bioRxiv2025

Functional Brain Imaging and Targeted Lesion Studies Using Manganese-Enhanced MRI and Focused Ultrasound in Non-Conventional ModelSpecies

Linking behavior to its neuroanatomical basis in non-conventional model species remains a significant challenge due to the scarcity of imaging and molecular tools. Commonly used approaches such as electrophysiological recordings rely on precise stereotaxic atlases or species-specific antibodies, while optogenetics requires transgenic lines which are largely unavailable beyond classical model organisms (e.g., mice, rats, zebrafish). Moreover, surgical lesion studies, a staple for verifying brain structure and behavior relationships, are logistically complex in species lacking atlases or living in aquatic environments. Here, we present a protocol integrating Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) and MR-guided High-Intensity Focused Ultrasound (HIFU) to overcome these limitations, which we demonstrate in the convict cichlid (Amatitlania nigrofasciata), a teleost fish lacking conventional neuroscience tools. MEMRI enables non-invasive, sub-millimeter resolution mapping of brain activity during behavior, and HIFU facilitates precise, surgery-free lesioning of targeted regions, adaptable to species without stereotaxic atlases. This combined approach offers a versatile, broadly applicable framework for linking brain structure and behavior in non-model organisms, advancing evolutionary and comparative neuroscience.

neuroscience↗