Foley, T. | Search bioRxiv

bioRxiv2025

FishFeats: streamlined quantification of multimodal labeling at the single-cell level in 3D tissues

SummaryCharacterizing the distribution of biological marker expression at the single cell level in whole tissues requires diverse image analysis steps, such as segmentation of cells and nuclei, detection of RNA transcripts (or other staining), or their integration (e.g., assigning nuclei and RNA dots to their corresponding cell). Several software programs or algorithms have been developed for each step independently, but integrating them into a comprehensive pipeline for the quantification of individual cells from 3D imaging samples remains a significant challenge. We developed FishFeats, an open-source and flexible Napari (Sofroniew et al. 2025) plugin, to perform all of these steps together within the same framework, taking advantage of available and efficient software applications. The primary core of our pipeline is to propose a user-friendly tool for users who do not have a computational background. FishFeats streamlines extracting quantitative information from multimodal 3D fluorescent microscopy images (smFISH expression in individual cells, immunohistochemical staining, cell morphologies, cell classification) to a unified "cell-by-cell" table for downstream analysis, without requiring any coding. Our second focus is to propose and ease manual correction of each step, as measurement accuracy can be very sensitive to small errors in the automatic process. Availability and implementationFishFeats is open source under the BSD-3 license, freely available on github: https://github.com/gletort/FishFeats. FishFeats is developed in python, as a Napari plugin for the user interface. Documentation is available in the github pages: https://gletort.github.io/FishFeats/.

developmental biology↗

bioRxiv2024

A cafeteria diet blunts effects of exercise on adult hippocampal neurogenesis but not neurogenesis-dependent behaviours in adult male rats

Animal studies have shown that a cafeteria (CAF) diet (high in saturated fat and sugar), is associated with memory impairments and increased anxiety, while exercise can enhance antidepressant-like effects and cognitive function. The mechanisms underlying the effects of a CAF diet, exercise, or their convergence on memory, mood and anxiety are not fully understood, but alterations in adult hippocampal neurogenesis (AHN), gut microbial metabolites, or plasma metabolic hormones may play a role. Therefore, this study investigated whether a 7.5-week voluntary running exercise intervention in young adult male rats could alter the effects of a concurrent CAF diet on depression-like, anxiety-like and cognitive behaviours and AHN, and determined associated changes in metabolic hormones and gut microbial metabolites. We found that exercise produced a mild anxiolytic effect, regardless of diet, and increased PYY, a hormone previously shown to reduce anxiety-like behaviour. CAF diet induced differential abundance of caecal metabolites, and exercise attenuated CAF diet-induced decreases in certain metabolites implicated in cognitive function or depression-like behaviour. Although exercise exerted antidepressant-like effects in the FST, induced subtle improvements in spatial learning strategy, and increased plasma metabolic hormones previously implicated in depression-like behaviour in CAF diet-fed animals, CAF diet blunted exercise-induced increases in plasma GLP-1 and AHN, suggesting that exercise should be accompanied by a healthy diet to increase AHN. Together, these findings highlight the importance of exercise and healthy diet for hippocampal health and provide insight into potential metabolite and hormone-mediated mechanisms underlying the effects of CAF diet and exercise on brain and behaviour. Key points- Diets high in saturated fat and sugar are associated with memory impairments and increased anxiety while exercise can exert antidepressant-like effects and enhance cognitive function, but the biological underpinnings of these effects and whether exercise can negate effects of such diets remain to be elucidated. - We found that running exercise modestly reduced anxiety in rats fed either a healthy or a cafeteria-style diet and increased a hormone (peptide YY) previously shown to decrease anxiety. - Running exercise exerted antidepressant-like effects in cafeteria diet-fed rats and attenuated cafeteria diet-induced decreases in gut metabolites previously implicated in cognition or depression-like behaviour. - Cafeteria diet blunted exercise-induced production of new neurons in the hippocampus, a brain region important in mood and memory. - These data highlight the importance of combining exercise with a healthy diet for hippocampal health, while identifying potential targets for intervention or dietary supplementation to prevent a cafeteria diet blunting beneficial effects of exercise

neuroscience↗

bioRxiv2024

Discovery of orally active SARS-CoV-2 papain-like protease (PLpro) inhibitors

Vaccines and first-generation antiviral therapeutics have provided important protection against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease (Mpro) have demonstrated clinical efficacy, known PLpro inhibitors have to date lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Herein, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

microbiology↗