Evaluated articles

Evaluation Summary:

This is a well conducted study that examines the potential role of senescent cells in fracture healing. Furthermore, the authors have used senolytic agents to examine if targeting cellular senescence will have a significant impact on fracture healing phenotype. The manuscript is succinctly written, and the methods and results are well described. These data provide the first demonstration for a potential role for cellular senescence in regulating fracture healing. The authors’ conclusions are largely supported by the experimental data.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript is of interest to scientists within the fields of actin cytoskeleton, cellular neurobiology and neurodevelopment. It explores how actin regulators are coordinated to trigger the formation of branches in neuronal dendritic arbor. Experiments are very well performed. Conclusions of the manuscript are convincingly supported by the results, although strict dependence of Cobl and Cobl-like in dendritic branch formation should perhaps be confirmed with additional experiments or tuned down. Results concerning the spatiotemporal relationship between the molecular players involved are more preliminary and few findings already published by the same group in previous articles should be expunged from this manuscript.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript unravels a detailed bipartite signaling mechanism, activation of which results in epithelial inflammation and cell motility. The paper is potentially of broad interest to cancer biologists and epithelial cell biologists. The data generated using the combination of genetic analyses, chemical inhibitors, and state-of-the-art confocal microscopy is of exceptionally high quality and supports the majority of the claims made in this paper.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study will be of interest to scientists involved in high-level vision. The data provide a compelling demonstration of the causal role of three key visual areas in context-based object recognition. The key claims of the manuscript are supported by the data, and are strengthened by the pre-registration of each of the three experiments.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

Capturing the rate and degree of protein turnover in tissues rich in collagen, proteoglycans and glycoproteins over the life span provides valuable information about how these tissues age and can increase our understanding of age-related disease. Using a Stable Isotope Labeling (SILAC) method to examine protein retention, new protein incorporation and protein turnover in three high collage content tissues, the authors show that turnover is low in older mice in these tissues, but the depth of the data generated provide a detailed examination of what low turnover means at a level we have not previously had. This paper would be of interest to a broad range of scientists studying connective tissues in the context of development and ageing.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper compares the properties of UV cone output synapses in different regions of the zebrafish retina using a combination of electron microscopy, quantitative imaging and computational modeling. They relate these differences to ultrastructural differences in synaptic ribbons and evaluate them using a previously-developed biophysical model for the operation of the synapse. The finding of regional differences in ribbon behavior is novel and suggests an under-appreciated degree of control of release by ribbon structure and behavior. The presentation of some of the results, particularly the model, could be strengthened.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

The authors assessed multivariate relations between a dimensionality-reduced symptom space and brain imaging features, using a large database of individuals with psychosis-spectrum disorders (PSD). Demonstrating both high stability and reproducibility of their approaches, this work showed a promise that diagnosis or treatment of PSD can benefit from a proposed data-driven brain-symptom mapping framework. It is therefore of broad potential interest across cognitive and translational neuroscience.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This study addresses an interesting and important question in evolutionary biology: how does the variance in fitness (components) vary between the sexes? In particular, it aims to evaluate whether there is a larger sex difference in systems with strong sexual selection. This study will be of considerable interest to researchers working on sexual coevolution and the role of sexual selection in promoting adaptation. However, there are some concerns regarding the limitations of the data and methods in support of the conclusions.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study utilizes holographic microscopy to study the swimming behaviour of flagellated forms of Leishmania mexicana in the presence or absence of host cell stimuli. Infective metacyclic promastigotes were found to swim faster than actively dividing procyclic promastigotes and to display different average trajectories. The swimming trajectories of these parasite stages were also altered in the presence of macrophages, promoting chemotaxis towards target host cells. The findings provide new insights into promastigote flagellar function and role of swimming behaviour in promoting pathogenesis.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This work combines 2D and 3D cryo-electron microscopy to show that cellular keratin intermediate filaments have heterogenous diameter, protofilament number and protofilament arrangement. This demonstrates the challenge for future high resolution structure determination of these essential filaments as well as providing the basis for understanding how this heterogeneity facilitates their function.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

Cohen and Baldassano present analyses of a large publicly available set of neuroimaging data from children and adolescents watching an animated movie, and is likely be of interest to neuroscientists interested in methods for analyzing naturalistic neuroimaging data, or those interested in the development of narrative processing in the brain. The results are not embedded in a strong theoretical framework and it is not yet clear which hypotheses are supported and which are refuted. However, the methodological approach developed here is a valuable addition to the repertoire of developmental neuroscience.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

The ability to fully resolve the whole genome of viral pathogens is often hampered by a multitude of different obstacles, one of which is optimally amplifying different regions of the genome. Part of this challenge lies in designing the best primers pairs that can consistently amplify PCR products despite the presence of changes (mutations) in the genome. The work described by Jaworski and colleagues can potentially provide an alternative approach that does not depend on primer pairs to fully sequence one such viral pathogen, SARS-CoV-2, and can also be applied towards other viral families.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

Understanding genes that control susceptibility to infection is critically important. In this manuscript Ji et al. identify the gene SP140 as the driving mutation resulting in susceptibility to a range of bacterial pathogens located within the severe susceptibility to tuberculosis (SST1) in mice. While our understanding of how SP140 functions remains unknown, the identification of a single gene within this locus that regulates Type I IFN is impactful and will be of broad interest for immunologists and microbiologists alike.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This study, which will be of interest to neuroscientists in the fields of learning and memory, somatosensation, and motor behavior, uses systems neuroscience tools to expand our view how the postero-medial (POm) nucleus of the thalamus contributes to goal-directed behavior. The reviewers suggested additional ontogenetic experiments to clarify the nature and specificity of those roles. They also indicated that certain alternative explanations to the experimental observations could be addressed for a more balanced presentation and interpretation of the results.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Vinbert et al. provide a conceptual replication on individual differences in conditioned skin conductance response during fear acquisition training and BOLD fMRI in a large sample (N=285) of healthy individuals (mono- and dizygotic twins). The authors report results that are in line with previous work and new results from a whole-brain analysis and suggest unique and shared contributions of individual brain regions. This is a timely and well-conducted replication study, the sample size is large for this area, and there are robustness (multiverse) analyses in place to ensure that findings are not driven by particular analysis choices.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This paper will be of interest both to marine biologists and to biophysicists studying voltage-gated proton channels. It describes cloning and full biophysical characterization of the first ion channel ever identified in reef-building coral species, and develops a mechanistic model for understanding regulation of voltage-gated proton channels.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This is a well-performed study that defines the role of purported host cell receptors in the entry of hantaviruses into human endothelial cells. This is an important study as it applies CRISPR-mediated deletion studies for candidate receptors in the same endothelial cell line (TIME).

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This article is of general interest to scientists who perform two-photon calcium imaging in vivo and explore the link between function and structure in real neural networks. The development of efficient approaches to estimate true correlations between large sets of noisy individual neurons based on realistic and thus limited observation time is a key to better understand functional local circuits. The effectiveness of the proposed method is illustrated by simulations and applied on real data, but several steps in its procedure remain to be clarified in the current form of the manuscript to be usable by a wide range of users.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

In this work, Holz and colleagues develop a computational stochastic model of lamellipodial actin network growth and turnover to address an unresolved important question: how do these networks remain wide enough, maintain angular order, and actually increase the filament length behind the leading edge? They compare the filament organization and rate of incorporation/detachment of actin subunits with experimental data published in the literature. A main result from this study is that frequent filament fragmentation and annealing are key events in the reorganization of branched actin networks. The paper is well written, contains very thorough and fair literature review, is accurate, well documented. The result is novel and significant.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

Cell movement is essential for development and tissue homeostasis. While the cellular machineries involved in movement have been well studied, how cells maintain a persistent direction of motion is less well understood. Here, Coppey's team shows that movement persistence emerges from the coupling of two cellular systems: protrusions at the leading edge and polarity of secretion. This coupling is controlled by the small GTPase Cdc42. The authors propose a physical model that recapitulates the coupling, defines two key parameters and explains persistent cell migration.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)