Evaluated articles

eLife Assessment

This study in the Drosophila antennal lobe, which contains multiple non-equivalent sensory channels, provides valuable new insight into how early-life sensory experience can produce lasting, cell-type-specific changes in neural circuit function. The work convincingly demonstrates that glial-mediated pruning during a defined developmental window leads to persistent suppression of odor responses in one olfactory neuron type, while sparing another. The evidence is solid and supported by multiple complementary approaches, although some mechanistic interpretations remain speculative and would benefit from additional functional testing.

eLife Assessment

The authors used three genetically diverse mouse models to investigate the impact of genome diversity on metabolic disease outcomes, such as obesity and glucose tolerance. This study is important because it integrates comprehensive metabolic analyses and multi-tissue phenotyping across sexes to reveal pathways relevant to obesity and its complications; the data are convincing and uncover several pathways that advance understanding of disease etiology while suggesting potential therapeutic avenues to prevent obesity-related health risks. There are limitations, such as a limited number of mouse strains used in the work, the 9-week feeding regime may be too short to capture full metabolic remodeling, and the mechanisms by which the immune-adipose axis impacts the broader phenotype are not fully described. Overall, the study is compelling, but the manuscript could be improved by justifying the strain selection, addressing the concern about the feeding duration, and providing stronger mechanistic support or discussion.

eLife Assessment

This work provides an important resource identifying 72 proteins as novel candidates for plasma membrane and/or cell wall damage repair in budding yeast, and describes the temporal coordination of exocytosis and endocytosis during the repair process. The data are convincing; however, additional experimental validation will better support the claim that repair proteins shuttle between the bud tip and the damage site.

eLife Assessment

This study provides valuable results on how entorhinal and hippocampal activity may support human thinking in perceptual spaces. It replicates the hexagonal symmetry of fMRI activity in the entorhinal cortex, reports novel findings on 3-fold symmetry in both behavioral performance and hippocampal fMRI activity, and links these results within a computational model. However, the methods – while potentially creative and interesting – are not fully justified or explained, and the conclusions remain incomplete. With further explanation, justification, and interpretation, this work could represent a significant step forward in understanding how cognitive maps are utilized.

eLife Assessment

This important manuscript presents a novel application of the SANDI (Soma and Neurite Density Imaging) model to study microstructural alterations in the basal ganglia of individuals with Huntington's disease (HD). The compelling methods, to our understanding, the first application of SANDI to neurodegenerative diseases, provide strong evidence for HD-related neurodegeneration in the striatum, account significantly for striatal atrophy, and correlate with motor impairments. The integration of novel diffusion acquisition and modelling methods with multimodal behavioural data are both of high value in their own right, and create a framework for future studies.

eLife Assessment

This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this work improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes HDX-MS to further understand the positive cooperativity between sugar and the co-transported sodium cation. Although the experimental work is solid, the presentation of the data lacks clarity, and in particular, the HDX-MS data interpretation requires further explanation in both methodology and discussion, as well as a clearer description of the new insight that is obtained in relation to previous studies. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

eLife Assessment

The study showcases a significant and important enhancement of the MAGIC transgenesis method, by extending it genome-wide to all chromosomes. The authors convincingly demonstrate that the MAGIC mosaic clones can be generated for genes from all, including the 4th chromosome. With this toolkit extension, the method is now most likely set to strongly rival the classical FRT/Flp recombination system for gene manipulation in flies.

eLife Assessment

This study provides valuable insights into human valve development by integrating snRNA-seq and spatial transcriptomics to characterize cell populations and regulatory programs in the embryonic and fetal outflow tract. The methods, data, and analyses are solid overall, but with some weaknesses that can be strengthened. The findings will be of interest to those who work in the field of heart development and congenital heart disease.

eLife Assessment

This manuscript describes a useful study describing an interesting infection phenotype that differs between adult male and female zebrafish. The authors argue that male-biased expression of Cyp17a2 is implicated in mediating infection levels through STING and USP8 activity regulation. Thus, this study highlights an unexpected factor involved in antiviral immunity that could open new avenues of investigation for infection, metabolism, and other contexts. Although the manuscript presents some evidence supporting its main claims, the evidence for the main argument made in the study on sex dimorphism remains incomplete at this stage.

eLife Assessment

This study presents valuable findings on the ability of a state-of-the-art method – temporally delayed linear modelling (TDLM) – to detect the replay of sequences in human memory. The investigation provides convincing evidence that TDLM has limitations in its sensitivity to detect replay when being applied to extended (minutes-long) rest periods, though a more thorough treatment of the relationship to prior positive findings would make the demonstration even stronger. The work will be of particular interest to researchers investigating memory reactivation in humans, especially using iEEG, MEG, and EEG.

eLife Assessment

The study by Reed et al. provides fundamental findings and convincing evidence defining the topological changes that occur during tumorigenesis. The findings enhance the understanding of stable long-range connections among genes that reprogram cancer-related functions. Nevertheless, performing additional experiments is recommended.

eLife Assessment

This manuscript reports important findings that have theoretical or practical implications beyond a single subfield. However, despite the combination of numerous analytical tools established and applied in the study, the work has substantial experimental limitations leading to incomplete evidence, indicating that the conclusions may be an over-interpretation of the findings.

eLife Assessment

This study presents a computational-experimental workflow for optimizing RNA aptamers targeting SARS-CoV-2 RBD. While the integrated approach combining docking, molecular dynamics, and experimental validation shows some promise, the useful findings are limited by the extremely weak binding affinities (>100 µM KD) and restriction to a single target system. The evidence is incomplete, with experimental design issues in the antibody competition assays and a lack of specificity testing undermining confidence in the conclusions.

eLife Assessment

This study is a valuable contribution to the evidence base. However, the evidence provided is incomplete as the study results only partially support the study conclusions. Addressing the methodological and reporting issues raised by the peer reviewers and properly aligning the claim made for providing a tool for early warning with the study analysis/results would improve the study quality and usefulness of its findings.

eLife Assessment

This valuable study introduces a non-perturbative pulse-labeling strategy for yeast nuclear pore complexes (NPCs), employing a nanobody-based approach in order to selectively capture Nup84-containing complexes for imaging and biochemical analysis. The data convincingly demonstrate that a short induction period (20 minutes to 1 hour) yields a strong and sustained signal, enabling affinity purification that faithfully recapitulates the endogenous Nup84 interactome. This tool offers a powerful framework for investigating NPC dynamics and associated interactomes through both imaging and biochemical assays.

eLife Assessment

This study reports on the development and characterization of chickens with genetic deficiencies in type I or type III interferon receptors, which is an important contribution to the field of avian immunology. The data reflecting the development of the new interferon-receptor-deficient chickens is compelling. However, the characterization of IFN biology and infection responses in these knockout chickens is somewhat incomplete and could be improved by addressing the noted weaknesses.

eLife Assessment

This important study examines the evolution of virulence and antibiotic resistance in Staphylococcus aureus under multiple selection pressures. The evidence presented is convincing, with rigorous data that characterizes the outcomes of the evolution experiments. However, the manuscript's primary weakness is in its presentation, as claims about the causal relationship between genotypes and phenotypes are based on correlational evidence. The manuscript needs to be revised to address these limitations, clarify the implications of the experimental design, and adjust the overall narrative to better reflect the nature of the findings.

eLife Assessment

Non-essential amino acids such as glutamine have been known to be required for T cell general activation through sustaining basic biosynthetic processes, including nucleotide biosynthesis, ATP generation, and protein synthesis. In this important study, the authors found that extracellular asparagine (Asn) is required not only for T cells to generally refuel metabolic reprogramming, but to produce helper T cell lineage-specific cytokine, for instance, IL17. In particular, the importance of Asn in IL17 production was convincingly demonstrated in the mouse experimental autoimmune encephalomyelitei (EAE) model, mimicking human multiple sclerosis disease.

eLife Assessment

This study presents valuable data suggesting that ATP-induced modulation of alveolar macrophage (AM) functions is associated with NLRP3 inflammasome activation and enhanced phagocytic capacity. While the in vivo and in vitro data reveal an interesting phenotype, the evidence provided is incomplete and does not fully support the paper's conclusions. Additional investigations would be of value in complementing the data and strengthening the interpretation of the results. This study should be of interest to immunologists and the mucosal immunity community.

eLife Assessment

This study illustrates a valuable application of BID-seq to bacterial RNA, allowing transcriptome-wide mapping of pseudouridine modifications across various bacterial species. The evidence presented includes a mix of solid and incomplete data and analyses, and would benefit from more rigorous approaches. The work will interest a specialized audience involved in RNA biology.