Evaluated articles

eLife Assessment

This potentially useful study introduces an orthogonal approach for detecting RNA modification, without chemical modification of RNA, which often results in RNA degradation and therefore loss of information. Compared to previous versions, the most recent one is improved and sufficiently aligned with the standards of the field to merit consideration by the research community, making the evidence solid according to said standards. Nevertheless, uncertainty regarding false positive and false negative rates remains, as it does for some of the alternative approaches. With more rigorous validation, the approach might be of particular interest for sites in RNA molecules where modifications are rare.

eLife Assessment

This important study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are convincing, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

eLife assessment

In this interesting study, the authors have used light-sensitive mGlu5 negative allosteric modulators to determine the role of these receptors in a chronic pain model. These findings could be useful to the pain field, but the evidence supporting these claims is incomplete.

eLife assessment

This study presents a useful examination of dense neuroanatomy in human postmortem medial entorhinal cortex, using a large number of small electron microscopy image volumes sampled from multiple cortical layers and individuals. The authors use solid experimental and annotation techniques, demonstrating the suitability of postmortem tissue reconstructions for analysis and presenting careful, detailed measurements of synapse properties and overall tissue composition. However, there is inadequate support connecting these findings to claims about general connectivity in medial entorhinal cortex, since factors affecting interpretability like noise, the spatial scales examined, and relationships between structural properties and connectivity are not characterized. With a more thorough contextualization, this work would be of interest for studies of cellular neuroanatomy or brain network organization.

eLife assessment

This computational work represents a valuable and long overdue assessment of the potential mechanisms associating patterns of activity of entorhinal grid cells, recorded mostly in rodents, with the population property of hexasymmetry detected in non-invasive human studies. The methodic comparison of alternative hypotheses is compelling, and the conclusions are important for the future design of experiments assessing the neural correlates of human navigation across physical, virtual, or conceptual spaces.

eLife assessment

This important study combines across multiple complementary neuroscientific methods to understand the neural response to visual stimulus complexity in the human brain across lifespan. Lalwani et al., provide solid evidence, drawing from appropriate and validated methodology. A weakness is that key information about methodological details and controls is still outstanding, as is a discussion on how generalizable the findings are. With these elements strengthened, the study would be of broad interest to neuroscientists and biologists interested in aging and sensory processing.

eLife assessment

This study presents a valuable finding on prognostic values of serum CA125, CEA, and AFP for predicting patient outcomes of endometrial cancer. The evidence supporting the claims of the authors is solid, although inclusion of detailed discussion of present results with prior documented findings would have strengthened the study. The work will be of interest to scientists working on endometrial cancer.

eLife assessment

How and why nutritional requirements change over development and differ between species are significant questions with wide-ranging implications spanning ecology to health. In this manuscript, Talal et al. set out to address these questions in laboratory and field experiments with grasshoppers and in a comparative analysis of different species. The laboratory experiments are convincing but the field and comparative aspects are not sufficiently well developed. In general, the study offers some evidence of a universal shift from high protein to high carbohydrate intake during ontogeny in animals, but the methods are not clear and/or appropriate to support the goals and conclusions of the manuscript as it is.

eLife assessment

This important manuscript used state-of-the-art techniques and employed relevant animal models to provide both convincing and solid evidence supporting the regulatory role of microRNA cluster 221/222 in rheumatoid arthritis synovial fibroblast. The findings of this work offer significant advances to current knowledge which will be interesting to a wide range audience in the rheumatology and bone research fields. However, whereas models, techniques, and analyses are solid, certain concepts related to the role of immune and bone cells are limited.

eLife Assessment

This important study by Liu and colleagues uses lineage tracing of hematopoietic stem and progenitor cells in situ to infer the clonal dynamics of adult hematopoiesis. The authors apply a new mathematical analysis framework enabling a wider range of clonal estimation and the revised study 1) provides evidence of polyclonal adult hematopoiesis, 2) provides insights on clonal dynamics during fetal liver hematopoiesis, and 3) reveals unexpectedly high polyclonality in a mouse model of bone marrow failure (Fanconi anemia), arguing against the prevalent views of clonal attrition in this context. The evidence in this extensively revised and improved study is compelling, with methods, data and analyses more rigorous than the current state-of-the-art, which will be of broad interest not only to stem cell and developmental biologists working on hematopoiesis, but also to researchers working on other systems.

eLife Assessment

This important study substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.

eLife Assessment

This important study is the first comprehensive analysis of the modulatory effects of nitric oxide (NO) on the response properties of retinal ganglion cells (RGCs) in the mouse retina using two-photon calcium imaging and multi-electrode arrays (MEA). The results provide compelling evidence that a subset of suppressed-by-contrast RGCs are affected. These unexpected findings are likely of broad interest to visual neuroscientists.

eLife assessment

Hartman et al.'s important research examines six commonly utilized imaging-based multiplexed transcriptomic techniques and introduces a novel specificity metric, "MECR," to streamline platform evaluations. The authors highlight the crucial influence of cell segmentation methodologies on outcomes, offering insight into the field. Nonetheless, the substantiation for the principal assertions remains incomplete, as the comparisons across platforms seem uneven due to variations in gene panels.

eLife Assessment

This valuable study marks a significant advancement in brain aging research by centering on Asian populations (Chinese, Malay, and Indian Singaporeans), a group frequently underrepresented in such studies. It unveils solid evidence for anatomical differences in brain aging predictors between the young and old age groups. Overall, this study broadens our understanding of brain aging across diverse ethnicities.

eLife Assessment

This study presents a valuable investigation into cell-specific microstructural development in the neonatal rat brain using diffusion-weighted magnetic resonance spectroscopy. The evidence supporting the core claims is solid, with innovative in vivo data acquisition and modeling, noting residual caveats with regard to the limitations of diffusion-weighted magnetic resonance spectroscopy for strict validation of cell-type-specific metabolite compartmentation. In addition, the study provides community resources that will benefit researchers in this field. The work will be of interest to researchers studying brain development and biophysical imaging methods.

eLife Assessment

The authors take a synthetic approach by introducing synaptic ribbon proteins into HEK cells to analyze how these assemblies cluster calcium channels at the active zone. Using a synapse-naive heterologous expression system and overexpression-based strategy is valuable, as it establishes a promising model for studying molecular interactions at the active zone. The study is built on a solid combination of super-resolution microscopy and electrophysiology, though it currently falls short of replicating the full functional properties of native ribbon synapses and instead resembles a multiprotein complex that partially mimics ribbon-type active zones.

eLife Assessment

This study presents an important finding on sperm flagellum and HTCA stabilization. The evidence supporting the authors' claims is convincing. The work will be of broad interest to cell and reproductive biologists working on cilium and sperm biology.

eLife Assessment

Notch1 is expressed uniformly throughout the mouse endocardium during the initial stages of heart valve formation, yet it remains unclear how Notch signaling is activated specifically in the AVC region to induce valve formation. To answer this question, the authors used a combination of in vivo and ex vivo experiments in mice to demonstrate ligand-independent activation of Notch1 by circulation induced-mechanical stress and provide evidence for stimulation of a novel mechanotransduction pathway involving post-translational modification of mTORC2 and Protein Kinase C (PKC) upstream of Notch1. These findings represent an important advance in our understanding of valve formation and the conclusions are supported by convincing data.

eLife assessment

In the revised version of this important study, the authors present a convincing pipeline for insect genome regulatory annotation across 33 insect genomes spanning 5 orders. Despite technical limitations in the field owing to the lack of comprehensive knowledge of enhancer content in any system, the authors employ several independent downstream analyses to support the validity of their enhancer predictions for a subset of these genomes. Taken together, the revised results suggest that this prediction pipeline may have uses in identifying functional enhancers across large phylogenetic distances. Reviewers note caveats that an experimental validation is not yet available in the field to validate a large class of newly identified enhancers across such evolutionary distances, and other pipelines might be of use to compare. This work will be of interest to the computational genomics, evolutionary biology, and gene regulation fields.

eLife Assessment

Veiga et al demonstrate the importance of incorporating RNAseq and machine learning approaches for neoantigen prediction. The evidence is convincing, and these findings contribute important information towards the selection of neoantigens for personalized antitumor vaccination.