Evaluated articles

eLife Assessment

This important study provides evidence, albeit still incomplete, that high-elevation species lose water at slower rates than low-elevation species. The findings imply that egg physiology may be a factor limiting the distributional range of bird species. While this work reinforces the need for all life stages to be considered when evaluating physiological adjustment to climate change, the analyses as presented by the authors do not clearly highlight the specific impact of species differences in influencing these adjustments.

eLife Assessment

In this manuscript, Jong et al. provide and validate a very useful resource for performing CRISPR screenings to study neutrophil differentiation and function by generating Hoxb8 cells that constitutively express Cas9. This library-screening approach has the potential to improve on the established lentiviral CRISPR-Cas9 editing of Hoxb8 cells. However, the technical advances provided are only incremental and the results presented in this study do not significantly further our understanding of these cells, but rather provide a good validation of their Cas9+ modified version.

eLife Assessment

In their study, Scherer and colleagues aim to use analyses of single-cell clones of murine granulocyte monocyte progenitors that are conditionally immortalized, and analyses of neutrophils derived from those clones to characterize an experimental system for studying neutrophil heterogeneity. The multi-omic and functional analyses reported are valuable but the strength of the evidence presented in support of them is incomplete because the study lacks a rigorous demonstration that the neutrophil-like cells that they derive are fully mature neutrophils.

eLife Assessment

This manuscript describes a useful integrated proteogenomics pipeline to enable the discovery of novel peptides in cancer cell lines. The method combines long-read RNA sequencing with a multi-protease digestion and proteomics approach. The method is a further development of the authors' previous approaches to identify cancer-specific peptides; however, the current study focuses on a single cell line, and the characterization remains incomplete and lacks validation for candidate alterations. The manuscript will be of interest to scientists focusing on identifying unique alterations in cancer cells.

eLife Assessment

This study demonstrates that endothelial toll-like receptor 4 is a central regulator of leptomeningeal inflammation in the context of neonatal E. coli meningitis. The data are derived from cell type-specific gene knockout in mice as well as from cultured endothelial cells, and are generally solid, with only minor weaknesses in analysis and interpretation. This work is important as it advances our understanding of host cellular processes and molecular pathways underlying meningitis pathogenesis.

eLife Assessment

This fundamental study advances our understanding of how dietary patterns shape cancer immunity by identifying a link between a Mediterranean-mimicking diet, gut bacteria, and a metabolite that enhances anti-tumor immune responses. The evidence supporting the main conclusions is solid, based on carefully controlled diet experiments, measurements of gut-derived molecules, and functional immune analyses across multiple models, together with supportive observations in human data. The work will be of broad interest to biologists working on microbiota and cancer. However, there are several issues that the authors should address to improve the manuscript.

eLife Assessment

The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this valuable manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. There are some concerns about the paper, particularly around Figures 1A, 1C, and 2E.

eLife Assessment

This study presents a valuable finding that depletion of the rRNA methyltransferase METTL5 enhances anti-tumor immunity through a novel mechanism involving neoantigen generation from non-canonical translation. The evidence supporting the central conclusions is solid, with comprehensive multi-omics data including ribosome profiling, immunopeptidomics, TCR sequencing, and multiple in vivo tumor models demonstrating synergy with immune checkpoint blockade.

eLife Assessment

Hoverflies are known for their sexually dimorphic visual systems and exquisite flight behaviors. This valuable study reports how two types of visual descending neurons differ between males and females in their motion- and speed-dependent responses, yet surprisingly, the behavior they control lacks any sexual dimorphism. The results convincingly support these findings, which will be of interest for studies of visuomotor transformations and network-level brain organization.

eLife Assessment

This useful study examines whether the sugar trehalose, coordinates energy supply with the gene programs that build muscle in the cotton bollworm (Helicoverpa armigera). The evidence for this currently is incomplete. The central claim - that trehalose specifically regulates an E2F/Dp-driven myogenic program - is not supported by the specificity of the data: perturbations and sequencing are systemic, alternative explanations such as general energy or amino-acid scarcity remain plausible, and mechanistic anchors are also limited. The work will interest researchers in insect metabolism and development; focused, tissue-resolved measurements together with stronger mechanistic controls would substantially strengthen the conclusions.

eLife Assessment

This important study substantially advances the imaging toolbox available to neuroscientists by presenting a tunable Bessel (tBessel-TPFM) platform that enables high-speed volumetric two-photon imaging. The evidence supporting the novel methodology is convincing, with rigorous benchmarking and demonstrations of a wide range of neuroimaging applications covering vascular dynamics, neurovascular coupling, optogenetic perturbation, and microglial responses. The work will be of broad interest to neuroscientists and imaging system tool developers.

eLife Assessment

This is an important study that advances our understanding of the transition from quadrupedal to bipedal gait in a neuromechanical model of the Japanese macaque. The method and results are solid; the neuromusculoskeletal model successfully reproduces experimental data, and the stability analysis based on an inverted pendulum model effectively explains the effects of different transition strategies. However, the study would benefit from a more comprehensive sensitivity analysis. The findings are highly relevant for researchers in motor control, comparative physiology/biomechanics, and robotics.

eLife Assessment

This valuable study reports results showing how different neurons in the dysgranular retrosplenial cortex code spatial orientation. Specifically, the paper reports that some neurons maintain tuning for a single head direction across multi-compartmental environments, while other neurons are tuned to different head directions that reflect the geometry within each compartment. The study was viewed as likely to expand the field's understanding of directional tuning of neurons, but incomplete evidence was provided to support the conclusions.

eLife Assessment

The study investigates, from multiple angles, the still-debated function of insect rhodopsin-7 (Rh7). The authors present compelling results for its ancient phylogenetic origin across pan-arthropods, a non-visual role based on expression analyses in the fly brain, an unusual G-protein signalling pathway, and - using behavioural genetics - that Rh7 affects how Drosophila melanogaster interprets and responds to light-dark transitions. Through this, the work provides fundamental new insights into the evolution and function of non-visual opsins.

eLife Assessment

There is a perennial question in the field of birdsong: the contribution of the cerebellum to singing and processing song-related information. This study provides a valuable first step into this discussion, using electrophysiology of cerebellar neurons during a battery of assays, including singing and song playback. While the electrophysiological dataset here is novel and could shed light on key aspects of the neural control of vocal behavior, the evidence provided for the conclusions reached by the authors is currently incomplete.

eLife Assessment

This valuable study introduces miRTarDS, a novel computational framework that predicts microRNA-target interactions based on a publicly available pretrained Sentence-BERT language model and downstream classification analysis. The strength of the evidence is incomplete, as the evaluation framework relies on unreliable ground-truth and false sets. Furthermore, the analysis fails to compare miRTarDS against existing state-of-the-art biomedical language models.

eLife Assessment

This study makes a valuable contribution to our understanding of how the lipase regulator ABHD5 may control lipase activity through interactions with lipid droplets and cellular membranes. By combining multiscale molecular dynamics simulations with experimental approaches, the authors provide novel molecular insights into this membrane-protein interaction and present evidence suggesting that the regulatory mechanism depends on protein conformational changes and local membrane remodeling. While much of the evidence supporting the main conclusions is convincing, several aspects of the analysis, interpretation, and discussion remain incomplete. Overall, this work will be of interest to structural and molecular biologists working on lipid metabolism and membrane biophysics.

eLife Assessment

This valuable study highlights the challenge of identifying the role of immune imprinting in influenza immunity. The manuscript provides solid evidence that statistical support for imprinting depends heavily on model choice and can be found in the absence of imprinting due to age-related processes. However, the results are incomplete in that the impact of incorrectly modeling imprinting is not clear. The work will be of interest to researchers who study adaptive immunity in any system where imprinting may be observed.

eLife Assessment

This important study introduces NoSeMaze, a semi-naturalistic platform for continuous, high-dimensional tracking of social and cognitive behaviors in group-housed mice, and uses it to show that individual social rank is stable across changing social contexts. By integrating automated dominance measures, proactive social behaviors, and reinforcement-learning-based profiles, the authors demonstrate a novel framework for examining how stable individual differences shape social structure. The strength of evidence is solid, advancing our understanding that social hierarchy can be viewed as a trait-like dimension of individuality. Yet, the interpretation of dominance in this paradigm and its broader ecological meaning remains somewhat ambiguous. This work will be of broad relevance for behavioral neuroscience and social behavior research.

eLife Assessment

IL21R, being a key cytokine receptor for shaping the T follicular helper and B cell functions, utilizes two STAT family members, STAT1 and STAT3. The authors utilize the IL21R ENU-induced mutant, together with relevant in vitro and in vivo experiments, to dissect the function of STAT1 and STAT3. The approach by itself sounds reasonable, but the main conclusions are incompletely supported by the data presented in this manuscript.