Genetic predisposition and environmental factors, including psychological stress, play prominent roles in driving the development and progression of colorectal neoplasms. However, the mechanisms through which chronic stress drives the progression of colorectal neoplasm remain unclear. The gut microbiota is closely linked to chronic psychological stress (chronic stress) and colorectal neoplasms. Here, we found that chronic stress significantly promoted tumor growth in patients with colorectal cancer and mouse models of colitis-associated colorectal cancer, while concurrently reducing the abundance of Akkermansia muciniphila in fecal and tumor samples. Restoring the A. muciniphila abundance mitigated the tumor-promoting effects of chronic stress. Furthermore, we identified A. muciniphila outer membrane vesicles as key mediators of the protective effect of this microbe. In conclusion, A. muciniphila alleviates chronic stress-induced colorectal neoplasm growth by releasing outer membrane vesicles. These findings highlight a connection among chronic stress, the gut microbiota, and colorectal neoplasms, providing a theoretical foundation for therapeutic strategies aimed at managing tumor progression in patients with colorectal cancer experiencing chronic stress.

Salamanders provide excellent models for studying vertebrate evolution, development, and regeneration. To further advance the newt as a model organism in biology, we conducted draft genome sequencing of 20 Gb of an inbred newt (Pleurodeles waltl). As part of this study, the Hoxd11-d13 intergenic region is expanded by over 1 Mb owing to the massive insertion of repetitive sequences including newt-specific satellite DNA. Interestingly, Myod and Bmp4, genes that are typically involved in vertebrate development, are absent in salamanders. Co-option of Sodefrin Precursor-like Factor genes, which encode sex pheromone ligands, suggests a diversification of reproductive behavior among salamanders. Moreover, a limb enhancer of Shh, MFCS1/ZRS, retains its function, even though it is positioned approximately 5 Mb away from the promoter. Furthermore, we have identified a functional cis-element potentially associated with limb regeneration in this enhancer. The newt genome yields crucial insights into amphibian evolution, behavior, development, and regeneration.
© 2025 The Author(s).

Tauopathies share common features, including tau aggregation, which plays a central role in neurodegeneration. However, these disorders are highly heterogeneous, particularly in the spread of pathological tau species between cells. In Alzheimer's disease, intracellular tau aggregation is followed by a propagation between cells leading to a hierarchical pathway of neurodegeneration, whereas in other tauopathies, such as progressive supranuclear palsy (PSP), pathological tau remains largely confined within neurons and exhibits more limited spread. This variability raises the question of whether tailored treatments for each tauopathy might offer more therapeutic benefit. Hence, we designed two different immunological approaches using single domain antibody fragments, also called VHHs, to target intracellular and extracellular tau. This study aims to first evaluate the safety of these immunological tools on physiological tau and then their potential to slow disease progression.
We selected the pro-aggregative tau hexapeptide PHF6 as a common target for the VHHs. These VHHs were cloned in viral vectors allowing to compare two different expression systems: 1) intracytosolic expression to prevent tau accumulation (intraVHH) and 2) secretion into the interstitial fluid, to prevent tau spreading (extraVHH). By stereotactic injection of viral vectors, these VHHs were expressed in the brain of transgenic or wild-type mice and three readouts were studied: behavior, brain imaging and tau lesions.
We validated the correct addressing of intra- and extraVHHs. These two constructs were not associated with adverse effects, even in the absence of tau overexpression, in wild-type mice. Their efficacy was demonstrated in transgenic mouse tau models, either chronic long-term or in acute seeding with injections of human brain homogenates from Alzheimer's disease patients. They both can slow down several pathological effects (i.e. cognitive deficits, cerebral atrophy and neuronal hyperphosphorylation of tau).
This study is a proof of concept demonstrating that VHHs can be engineered to reduce both intra- and extracellular tau pathologies without major adverse effects, making them of interest for therapeutic applications.
© 2025. The Author(s).

Anterior-posterior axis formation in the mouse embryo requires the active migration of the DVE cell population at E5.5. While intracellular Ca2+ signaling has been shown to control cell migration in multiple cell contexts, it is unknown whether it is required for DVE migration. The pattern of Ca2+ activity in the mouse embryo at early peri-implantation stages is also unknown. Using the GCaMP6f Ca2+ reporter line, we performed a detailed assessment of Ca2+ dynamics between E0.5 and E5.5 using live imaging. We find that prior to implantation, Ca2+ transients are rare, but at E5.5 widespread, periodic, Ca2+ transients in extraembryonic tissues can be observed, including in the VE and ExE. In contrast, cells of the E5.5 epiblast remain relatively quiescent but show sporadic large-scale multicellular waves. Inhibition of SERCA at E5.5 abolishes Ca2+ transients and leads to DVE arrest, indicative that these transients are required for axial patterning. Together, these results reveal the pattern of Ca2+ handling in the early mouse embryo and a novel requirement in anterior-posterior axis formation.
Copyright: © 2025 Stower et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.