Evaluated articles

eLife Assessment

This fundamental study presents a new method for longitudinally tracking cells in two-photon imaging data that addresses the specific challenges of imaging neurons in the developing cortex. It provides compelling evidence demonstrating reliable longitudinal identification of neurons across the second postnatal week in mice. The study should be of interest to development neuroscientists engaged in population-level recordings using two-photon imaging.

eLife Assessment

This work describes the establishment of an image analysis pipeline for signal correction, segmentation and quantitative data analysis of multilayered organoid and tumoroid systems. The revised study is important for the field to address many practical challenges in deep-tissue visualization. The image analysis pipeline is well-designed and compelling.

eLife Assessment

This is a fundamental study providing molecular insight into how cross-talk between histone modifications regulates the histone H3K36 methyltransferase SETD2. The manuscript contains excellent quality data, and the conclusions are convincing and justified. This work will be of interest to many biochemists working in the field of chromatin biology and epigenetics.

eLife Assessment

In this important manuscript, Cassell and colleagues set out on a mechanistic and pharmacological exploration of an engineered chimeric small conductance calcium-activated potassium channel 2 (SK2). They show compelling evidence that the SK2 channel possesses a unique extracellular structure that modulates the conductivity of the selectivity filter, and that this structure is the target for the SK2 inhibitor apamin. The interpretations are sound and the writing is clear, and the manuscript was strengthened during review by providing more detailed information for the electrophysiological experiments and the structural analyses attempted, in addition to relating dilation of the filter to mechanisms of inactivation in other potassium channels. This high-quality study will be of interest to membrane protein structural biologists, ion channel biophysicists, and chemical biologists, and will help to inform future drug development targeting SK channels.

eLife Assessment

This valuable work used molecular biology, cell biology, and genetic approaches to unravel individual genes and potential pathways that contribute to paternal mitochondrial inheritance using C. elegans as the model organism. Their microscopy method is cutting edge, with sufficient biological replicates, proper control, and appropriate statistics. These findings are convincing and are of general interest for understanding mitochondrial inheritance in C. elegans, which could have implications for understanding similar biological processes in other organisms.

eLife Assessment

The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide compelling data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.

eLife Assessment

This study presents a valuable technical advance in the long-term live imaging of limb regeneration at cellular resolution in Parhyale hawaiensis. The authors develop and carefully validate a method to continuously image entire regenerating legs over several days while minimizing photodamage and optimizing conditions for robust cell tracking, together with post-hoc in situ identification of cell types. The data are convincing, the methodology is rigorous and clearly documented, and the results will be of interest to researchers in regeneration biology, developmental biology, and advanced live imaging and cell tracking software development.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This manuscript by Li, Lu et al., presents important findings on the role of cDC1 in atherosclerosis and their influence on the adaptive immune system. Using Xcr1Cre-Gfp Rosa26LSL-DTA ApoE-/- mouse models, these data convincingly reveal an unexpected, non-redundant role of the XCL1-XCR1 axis in mediating cDC1 contributions to atherosclerosis.

eLife Assessment

This important work challenges current models of merozoite surface protein function by showing that MSP2 is dispensable for parasite growth while modulating immune responses to AMA1, with implications for malaria vaccine design. The conclusions are supported by compelling experimental evidence, including state-of-the-art technologies and well-characterized monoclonal antibodies. These findings provide new insights into immune evasion and antigen targeting that will be of broad interest to parasitology, immunology, and vaccine researchers.

eLife Assessment

This important study introduces a Bayesian method to determine bacterial counts that accounts for the experimental noise inherent to dilution and plating methods, and distinguishes it from biological uncertainty. The evidence supporting the conclusions is convincing, combining simulated data and experimental data. The method will be of interest to microbial ecologists, and potentially to the broader community interested in inference from biological data, even more so if the domain of application and the limitations are further clarified.

eLife Assessment

This valuable study presents an innovative noninvasive immunotherapeutic strategy for hepatocellular carcinoma by combining ultrasound stimulation with calcium-loaded nanodroplets to activate splenic immune responses. The authors provide solid preclinical data, including single-cell transcriptomic analyses and evidence of tumor growth suppression, supported by a creative and well-executed methodology. Further validation of the calcium signaling mechanisms and assessment of long-term safety will strengthen the translational potential of this approach. The work will be of broad interest to researchers in oncology, immunotherapy, and biomedical engineering.

eLife Assessment

This study introduces ambisim, a rigorously validated and well-documented simulation framework that enables the generation of synthetic, genotype-aware single-cell RNA and ATAC sequencing datasets under realistic conditions. The authors provide solid evidence of its utility by benchmarking multiple demultiplexing methods and proposing a new variant consistency metric. While the tool is valuable for guiding method selection, the interpretation of the new metric requires further clarification.

eLife Assessment

This study presents a valuable finding on the neural representation of time from two distinct egocentric and allocentric reference frames. The evidence is solid and largely supports the hypothesis, with one caveat that the task differences could impact the observed effects. The work will be of interest to cognitive neuroscientists working on the perception and memory of time.

eLife Assessment

This important study describes a computational model of the rat spinal locomotor circuits and how they could be plastically reconfigured after lateral hemisection or contusion injuries to replicate gaits observed experimentally in vivo. Overall, the simulation results convincingly mirror the gait parameters observed experimentally. The model suggests the emergence of detour circuits after lateral hemisection, whereas after a midline contusion, the model suggests plasticity of left-right and sensory inputs below the injury.

eLife Assessment

This important study fills a gap in our knowledge of the evolution of GPCRs in holozoans, as well as the phylogeny of associated signaling pathway components such as G proteins, GRKs, and RIC8 proteins. The evidence supporting the conclusions is compelling, with the analysis of extensive new genomic data from choanoflagellates and other non-animal holozoans. Overall, the study is thorough and well-executed. It will be a resource for researchers interested in both the comparative genomics of multicellularity and GPCR biology more broadly, especially given the importance of GPCRs as highly druggable targets

eLife Assessment

The manuscript by Ross, Miscik, and others describes an intriguing series of observations made when investigating the requirement for podxl during hepatic development in zebrafish. Understanding how genetic compensation pathways are involved in gene function is an important question. However, there is incomplete evidence provided in the manuscript at this point to conclude that discrepancies between observed phenotypes are due to genetic compensation.

eLife Assessment

In this important study, the authors set out to determine the molecular interactions between the AQP2 from Trypanosoma brucei (TbAQP2) and the trypanocidal drugs pentamidine and melarsoprol to understand how TbAQP2 mutations lead to drug resistance. Using cryo-EM, molecular dynamics simulations, and lysis assays the authors present convincing evidence that mutations in TbAQP2 make permeation of trypanocidal drugs energetically less favourable, and that this impacts the ability of drugs to achieve a therapeutic dose. Overall, this data will be of interest for those working on aquaporins, and development of trypanosomiasis drugs as well as drugs targeting aquaporins in general.

eLife Assessment

This valuable manuscript presents findings supported by solid data to identify a surprising glia-exclusive function for betapix in vascular integrity and angiogenesis. The manuscript also describes the optimisation of a modified CRISPR-based Zwitch approach to generate conditional knockouts in zebrafish

eLife Assessment

This useful study provides a spatial transcriptomic analysis of the mouse adrenal gland that could have implications for future research and applications. The authors present solid results that allow the dissection of the cell signalling pathways and cellular composition of different zones of the adrenal glands in the mouse model; they propose new zone-specific gene markers and specific intra- and inter-zonal signaling pathways based on receptor-ligand expression patterns. Their web tool is user-friendly and will be helpful for adrenal scientists; however, the validation of crucial results of the large dataset is necessary. There are also several contradictory results/interpretations, and the opportunity to dissect the sexually dimorphic gene expression pattern and mouse-human interspecies differences is a missed opportunity.

eLife Assessment

This important study explores the role of SIRT2 in regulating Japanese encephalitis virus replication and disease progression in rodent models. The findings presented are novel as sirtuins are known for their roles in aging, metabolism, and cell survival, but have not been studied in the context of viral infections until recently. The evidence supporting the claims is solid, although additional experiments to further characterize the clinical outcomes and directly test the link between acetylated NF-kB and SIRT2 expression would have strengthened the study. The work will be of interest to biologists studying viruses, sirtuins, and inflammation.