Evaluated articles

eLife Assessment

This study characterizes a potentially targetable mechanism by which phosphate scarcity drives polymyxin B resistance in Enterobacteriaceae. The findings are important. While some aspects of the approach are very strong, particularly the diversity of techniques, it is recommended to include genetic controls and antibiotic resistance experiments in order to strengthen the evidence, which is currently solid. The clarity and presentation of the findings could also be improved.

eLife Assessment

This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiates developmental retinal Ca²⁺ waves and coordinates microglial activation and vascular outgrowth during postnatal maturation. The work is important because it proposes an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. Although the mechanistic conclusions would benefit from complementary genetic validation, the study provides a convincing foundation for future investigations into the coordination of neural circuit development and tissue remodeling.

eLife Assessment

This is an important study that establishes a zebrafish model of PIK3CA-related overgrowth syndrome. The imaging characterization of the mesodermal, particularly vascular, lesions of the model is compelling. The scRNA-Seq analysis is convincing, revealing key perturbations in the PIK3CA-mutation model, although deeper investigation of the exact mechanism leading to the lesions, as well as validation at different time points, could further strengthen the findings. This work will be of interest to medical biologists working on PROS, and potentially to a broader audience interested in non-cell-autonomous signaling of PIK3CA and its implications in other diseases.

eLife Assessment

This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools is characterized by exceptional evidence after a thorough revision.

eLife Assessment

This valuable study provides the first broad cross-species evolutionary analysis of the pir multigene family in malaria parasites, showing that the family evolved through rapid duplication and loss while retaining a small number of conserved orthologs with essential functions. The authors identify pirC1 as a key determinant of parasite growth across multiple Plasmodium species. However, the work remains incomplete because the mechanistic role of PIRCl and its precise subcellular localization are not directly resolved.

eLife Assessment

This study makes an important contribution by broadening the range of eukaryotic model systems and establishing Blastocystis, the most prevalent microeukaryote in the human gut, tractable for reverse-genetics investigations. The presented imaging data are convincing and informative. The work should interest readers studying host-microbe interactions in the human gut, as well as those developing new systems for eukaryotic research.

eLife Assessment

In this manuscript, the authors investigate programmed DNA elimination (PDE) across nematodes using a large-scale cytological approach. This work is potentially significant because it expands PDE beyond a few known nematodes to a much broader set of Rhabditidae species, providing an important resource for investigating PDE's evolutionary origins and functions. The strength of evidence, however, is incomplete; the technique used to evaluate PDE is insufficient to provide unambiguous support for the phenomenon, so additional methods, such as genomic sequencing from a few species spanning the range of elimination levels, would be required to confirm these findings. This research would be of interest to geneticists, evolutionary biologists, and those working on the regulation of genome integrity.

eLife Assessment

This is a fundamental study of individual variation and the contribution of learning to behavioural individuality. The experimental design of massively parallel behavioural phenotypes is outstanding and the conclusions are supported by a compelling and rigorous analysis across a large number of experiments in thousands of individuals across genotypes and conditions. The dataset further represents an advance in studying visual associative learning thanks to the ability to make longitudinal measurements of many behavioural decisions within the same animals. These results are a major contribution to the understanding of the sources of behavioural individuality.

eLife Assessment

This study presents valuable findings on phase-separated condensate formation by the MUT-16 protein, which plays a key role in small RNA biogenesis. A detailed analysis of the interactions governing condensate formation was carried out using coarse-grained and all-atom molecular dynamics simulations, complemented by in vitro phase separation experiments. While many of the results appear solid, a number of technical details are lacking, the computational part appears incomplete and would benefit from additional analyses and clarifications, and the novelty of the study should also be clarified, particularly in comparison with the authors' previous work on MUT-16. Overall, the work will be of interest to biophysicists and molecular biologists studying phase separation and biomolecular condensates.

eLife Assessment

Overall, this is an important manuscript that delivers an invaluable community resource. The execution is relatively simple, but the evidence of this resource is solid. The effort invested in generating the knockout lines that for validation experiments is a clear strength of the study, but it doesn't substitute for a careful evaluation of the same reagents in the end-users' specific protocols before making any biological statement.

eLife Assessment

This important study provides a quantitative comparison of how zebrafish and medaka larvae process visual motion, revealing clear differences in how they integrate information across space and time. The evidence is convincing, combining a broad set of behavioral assays with response decomposition and mechanistic modeling that together support the central conclusions. Some aspects remain incomplete, particularly the link between the spatial and temporal findings, the extent to which the model accounts for the full range of behavioral results, and the framing of broader evolutionary or social interpretations. Overall, the work offers a careful and informative analysis that should be of broad interest to researchers studying visual processing, sensorimotor computation, and comparative neuroscience.

eLife Assessment

This study presents a large-scale characterization of single-neuron responses during reading and listening, enabling examination of both 'low-level' (orthographic/phonological) and 'higher-level' (syntactic) features, as well as links between single-neuron activity and multi-scale field potentials, making it a valuable resource for bridging micro- and macroscale accounts of language processing. The analyses identify modality-specific and putatively modality-independent responses across distributed brain regions, offering an intriguing framework for understanding how sensory-specific and abstract representations may relate. However, the evidence supporting the central claims is currently incomplete, due to limited population-level quantification, insufficient statistical characterization of how many neurons encode the relevant features, ambiguity in the interpretation of encoding model results, and a lack of rigorous tests of cross-modal generalization and alternative accounts, which together weaken the conclusions about amodal representations and hierarchical processing.

eLife assessment

This is a valuable survey of movements and locomotor patterns produced by circuits in the medial reticular formation (MRF) of the brainstem. The authors provide solid evidence that activation of GABAergic MRF neurons slowed down walking, activation of glutamatergic neurons induced a specific "shuffle" limb trajectory, and the activation of serotonergic neurons increased locomotor speed without affecting walking signature. This study adds to the growing body of knowledge about the effects of brainstem circuits on specific aspects of locomotor function.

eLife Assessment

This potentially valuable study investigates the anti-senescence effects of red light exposure, proposing that reduced SIRT4 levels enhance fatty acid metabolism and H3K9ac, thereby attenuating ageing-related phenotypes. The authors use multiple approaches, including cultured cells, animal models, and molecular analyses, to support their conclusions. However, the evidence remains incomplete, as additional controls and stronger mechanistic data are needed to fully support the proposed pathway, particularly how red light exposure reduces SIRT4 levels.

eLife Assessment

The study presents valuable findings regarding the impact of ARHGEF6 deletion, a RhoGTPase regulator linked to X-linked intellectual disability (XLID46), in the development of interneurons. The evidence supporting the observed cellular and developmental phenotypes collected in both mouse and human iPSC models is convincing, although further work would strengthen the mechanistic interpretation and clarify the specificity of the findings. This work offers new insights into ARHGEF6 function and the potential contribution of its dysfunction to neurodevelopmental disorders.

eLife Assessment

The manuscript by Rotsides et al. reports the design and validation of SMART-MR1, a miniaturized MR1 metabolite-display platform in which the α1/α2 ligand-binding domain is stabilized by a synthetic helical domain in place of the α3 domain and β2-microglobulin. Supported by biochemical, biophysical, and structural approaches, including ITC, NMR, and cryo-EM, the work provides solid evidence that SMART-MR1 retains native-like ligand binding and A-F7 TCR recognition while enabling experimental approaches for ligand screening that are difficult with conventional MR1 constructs. The study is valuable for the MR1 and MAIT-cell fields, particularly as a tool for ligand screening and mechanistic studies of MR1-restricted antigen presentation. There are several suggestions to further strengthen the study's impact, including clearer benchmarking against existing MR1 platforms, broader validation across ligands and TCRs, and functional evidence from MAIT-cell staining or activation assays.

eLife Assessment

This important study examines the effects of diet and exercise on brain structure and behaviour in the 3xTg mouse model of Alzheimer's disease. They show that combined access to a low-fat diet and exercise improves regional brain volume and behaviour in transgenic and wild-type control mice in a sex-specific manner, with analyses linking functional improvements to glucose homeostasis. Although some claims are well supported, the overall strength of the evidence is incomplete and hampered by a lack of clarity regarding the statistical analyses chosen. The work may be of interest to researchers studying neurodegenerative disease, particularly in preclinical contexts.

eLife Assessment

This study provides invaluable insights into the field of genomic prediction of traits by demonstrating how machine learning algorithms can integrate genomic and transcriptomic data and handle nonlinearity, providing important comparative prediction results across environments. The rationale and analyses conducted to integrate the two types of ~omics datasets in two environments are solid. The work will be of interest to plant geneticists and breeders, especially those interested in the genetics of environmental adaptation.

eLife Assessment

This manuscript provides important insights into how U2AF2-dependent intron retention regulates the localization and function of long noncoding RNAs, with evidence supported by multiple complementary approaches. The work is notable for linking intron retention to nuclear speckle localization and cellular phenotypes, including proliferation and migration, although the mechanistic basis remains incompletely resolved. Overall, the study presents a compelling dataset with clear biological implications but would benefit from additional analyses to strengthen mechanistic interpretation and generality.

eLife Assessment

This potentially useful paper presents an intriguing hypothesis about the evolutionary origins of the SLC25 family of mitochondrial carrier proteins common to all eukaryotic life, proposing that all members originated from the ADP/ATP carrier (AAC) and that AAC itself may have emerged from bacterial homologs such as CysZ and YihY. While the phylogenetic analyses and structural searches are reasonable methodologies to explore ancient evolutionary events, the evidence provided here is deemed to provide incomplete support for the conclusion that the mitochondrial ATP transporter is related to CysZ and Yih.