Evaluated articles

eLife Assessment

This study thoroughly assesses tactile acuity on women's breasts, for which no dependable data currently exists. The study provides two important contributions, by convincingly showing that tactile acuity on the breast is poor in comparison to other body parts, and that acuity is worst in larger breasts, indicating that the number of tactile sensors is fixed. However, further arguments concerning the role of the nipple in spatial localisation are not well supported by the current evidence, therefore diluting the overall contribution of the study. This study will be of interest to the broader community of touch, as well as those interested in breast reconstruction and sexual function.

eLife Assessment

This manuscript provides potentially important findings examining in 2D and 3D models in MYC liver cancer cells changes in DNA repair genes and programs in response to hypoxia. The authors use convincing methodology in most cases, but there is some concern that the analysis is incomplete.

eLife Assessment

This manuscript provides important findings for understanding the mechanisms of a major gene causing the gonad of fish and other vertebrates, including mammals, to become an ovary rather than a testis. Evidence is solid, but alternative explanations for a number of the claims must be considered and discussed. The impact of the work would benefit by placing it in a richer historical context.

eLife Assessment

This useful study provides convincing evidence that Drosophila can taste cholesterol through a subset of bitter-sensing gustatory receptor neurons, and that flies avoid high-cholesterol food. However, the same receptors have been previously found to be involved in the detection of multiple seemingly unrelated chemicals, and the reported expression patterns of these receptors contradict past reports. These caveats are not mentioned in the paper, raising critical concerns about the study's conclusions.

eLife Assessment

This important study utilizes single-cell RNA sequencing to reveal the heterogeneity of trans-sialidase-like superfamily gene expression in Trypanosoma cruzi populations. The approach is highly convincing, as it successfully assigns cells to specific developmental forms and highlights the variability in surface protein expression among trypomastigotes. However, while the findings are solid and contribute to the understanding of immune evasion mechanisms, the study would benefit from a more detailed exploration of the regulatory factors governing trans-sialidase expression. Strengthening this aspect would further enhance its impact on researchers studying T. cruzi pathogenesis and host-parasite interactions.

eLife Assessment

This valuable study provides a comprehensive description of the Nematostella vectensis matrisome - the genes encoding the proteins of the extracellular matrix. The authors combine new mass spectrometry data with bioinformatic analyses of previously published genomic and single-cell RNAseq data. The analysis is thorough, and the discussion and conclusions are convincing. This work will be of interest to biologists working on the evolution of the matrisome, as well as more broadly those working with non-bilaterian animals.

eLife Assessment

The development of glmSMA represents a valuable advancement in spatial transcriptomics analysis, offering a mathematically robust regression-based approach that achieves higher-resolution mapping of single-cell RNA sequencing data to spatial locations than existing methods. The evidence is convincing, as the authors demonstrate the method's superiority by formulating it as a convex optimization problem that ensures stable solutions, coupled with successful validation across multiple biological systems. The rigorous mathematical framework and validation across diverse tissues enable precise spatial mapping of cellular heterogeneity at enhanced resolution.

eLife Assessment

This study reanalyzed previously published scRNA-seq and TCR-seq data to examine the proportion and characteristics of dual-TCR-expressing Treg cells in mice, presenting some useful insights into TCR diversity and immune regulation. However, the evidence is incomplete, particularly with respect to data interpretation, statistical rigor, and the functionality of dual -TCR Treg cells. The study is potentially of interest to immunologists studying T-cell biology.

eLife Assessment

Kwon et al. present an important paper using a novel approach to estimating rotavirus vaccine efficacy using data from a passive surveillance network in the US. They provide convincing evidence to support their conclusion that using the whole genome, rather than previous use of two surface proteins, enhances our understanding of strain-specific vaccine efficacy. These findings have implications for this vaccine specifically as well as type-specific vaccine evaluation more generally.

eLife Assessment

In this manuscript, Lim and collaborators present an important system for developing self-amplifying RNA with convincing evidence that it does not provoke a strong host inflammatory response in cultured cells. This approach could be further strengthened going forward by testing these self-amplying RNAs in an in vivo system.

eLife Assessment

This study shows, for the first time, the structure and snapshots of the dynamics of the full-length soluble Angiotensin-I converting enzyme dimer. The combination of structural and computational analyses provides compelling evidence that reveals the conformational dynamics of the complex and key regions mediating the conformational change. This fundamental work illustrates how conformational heterogeneity can be used to gain insights into protein function.

eLife Assessment

This study presents a useful contribution to understanding zinc regulation of sperm physiology, specifically its inhibitory effects on the sperm-specific potassium channel Slo3. However, the evidence supporting the claims is incomplete, as critical experimental controls are lacking, key mechanistic aspects remain insufficiently explored, and experimental descriptions are often inadequate, making it difficult to fully assess the findings. Strengthening the study with additional electrophysiological recordings in sperm cells, improved imaging controls, and clearer methodological descriptions would enhance its impact and rigor.

eLife Assessment

This report explores the role of matrix metalloprotease MMP21 in left-right patterning in Xenopus. Based on a series of compelling experiments, the authors demonstrate that MMP21 can be secreted and acts upstream of dand5 without affecting cilia flow. The experiments are interesting and valuable; however, the claims by the authors lack consideration of other models that could also explain their findings.

eLife Assessment

This important study addresses a topic that is frequently discussed in the literature but is under-assessed, namely correlations among genome size, repeat content, and pathogenicity in fungi. Contrary to previous assertions, the authors found that repeat content is not associated with pathogenicity. Rather, pathogenic lifestyle was found to be better explained by the number of protein-coding genes, with other genomic features associated with insect association status. The results are considered solid, although there remain concerns about potential biases stemming from the underlying data quality of the analyzed genomes.

eLife Assessment

This manuscript demonstrates that Oct4 overexpression synergizes with Notch inhibition (Rbpj knockout) to promote the conversion of adult murine Müller glia (MG) into bipolar cells. These findings are important as the authors used rigorous genetic lineage tracing (GLAST-CreER; Sun-GFP) to confirm that neurogenesis indeed originates from MGs, addressing a key issue in the field. The single-cell multiomic analyses are compelling, and while functional studies of MG-derived bipolar cells would strengthen the conclusions, they are beyond the scope of this study.

eLife Assessment

The manuscript presents some useful accounts of experiences funding team projects within the BRAIN Initiative. These would be more appropriate to add to the companion manuscript since the present manuscript contains some overlapping analyses and does not stand well on its own. Therefore the evidence supporting the conclusions is incomplete.

eLife Assessment

The authors provide a convincing summary of ten years of Brain Initiative funding including the historical development, the specific funding mechanisms, and examples of grants funded and work produced. It is particularly valuable at this moment in history, given the cataclysmic changes in the US government structure and function occurring in early 2025.

eLife Assessment

This important computational study investigates homeostatic plasticity mechanisms that neurons may employ to achieve and maintain stable target activity patterns. The work extends previous analyses of calcium-dependent homeostatic mechanisms based on ion channel density by considering activity-dependent shifts in channel activation and inactivation properties that operate on faster and potentially variable timescales. The model simulations convincingly demonstrate the potential functional importance of these mechanisms.

eLife Assessment

This fundamental study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. The authors test the impact of procedural alterations made in another study, by Gainey et al., which claimed that transgenerational inheritance in this paradigm lacks robustness, despite this observation having been reported in multiple papers from the Murphy lab. The authors of the present study show that by following a non-standard avoidance protocol, Gainey et al. likely biased their measurements in a way that made it hard to observe learned avoidance. The authors also highlight the importance of bacterial growth conditions, showing that expression of the trigger molecule, the bacterial P11 RNA, which is necessary and sufficient to drive the transgenerational inheritance of the avoidance phenotype, is influenced by temperature. As expression of P11 was not verified by Gainey et al., this provides another explanation for the inability to observe transgenerational epigenetic inheritance. Together, the authors provide compelling and powerful arguments that the original phenomenon is robust and that it can be reproduced in the Murphy lab by following their original protocol precisely, including the use of azide to immobilize the worms at the food source. Overall, this study not only provides guidance for investigators in this experimental paradigm, but it also provides additional understanding of the differences between naïve preference, learned preference, and transgenerational epigenetic inheritance. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.