Evaluated articles

Evaluation Summary:

This work traces at the protein domain level the associations made within droplets containing RNA-binding protein FUS and how they change as a function of time (and maturity), in the presence and absence of the small heat-shock protein HSPB8, by chemical cross-linking coupled to mass spectrometry. This work is an important step forward in our general understanding of the macromolecular interactions within liquid-liquid phase-separated protein droplets, and how they are regulated by small heat-shock protein molecular chaperones.

(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, #2, and #3 agreed to shares their name with the authors.)

Evaluation Summary:

The paper describes novel structures of a protein recently reported to function as a mechanosensitive ion channel. Surprisingly, the structures and functional data rather support the formerly suggested role of this protein in lipid metabolism. The paper is of relevance for ion channel field and for those interested in fatty acid metabolism.

(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 article will be of interest to behavioural ecologists studying aggression, within-group conflict, communication, and the use of social information. The study elegantly combines well-designed experiments with field observations to investigate the effects of within-group conflict on social behaviour. Specifically, it expands our understanding of social dynamics in group-living species by providing evidence that bystanders of within-group conflict may play a role in maintaining group cohesion. The findings provide a valuable contribution, and contrast, to existing work in this field.

(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 builds upon the previous original work of the authors by identifying a pathway that regulates collagen nanostructure and stiffness in lung fibrosis and demonstrating that this pathway it is independent of pathways regulating collagen synthesis. The analysis performed to validate the specificity of experimental findings and the demonstration that HIF activation is required for the increased tissue stiffness associated with fibrosis are elegant and convincing. With some additional clarifications and controls, this manuscript will be of broad interest to researchers interested in lung biology and especially to those focused on the pathogenesis and therapy of lung fibrosis.

(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 work is of interest to readers in the field of genome stability, DNA repair and associated human diseases. The manuscript describes systematic analyses of the crucial DNA repair mediator BRCA2 and its variants lacking the DNA binding domain or RAD51 interacting C-terminal domain, and the conclusions present a conceptual advance as to how BRCA2 promotes DNA repair. The work is a technical tour de force that includes evaluation of the DNA damage response, gene targeting and single particle tracking in mouse embryonic stem cells, as well as biophysical analyses of the human counterparts. The key claims of the manuscript are largely supported by the 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. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

Razzauti and Laurent investigate the formation of extracellular vesicles (EVs) by the cilia of C. elegans sensory neurons and the potential functions of this process. Consistent with previous findings, they show that EVs can be released from two distinct sites of the cilium; further, they show that several different classes of sensory neurons can produce EVs, that these can be taken up by a neighboring glial cell, and that this process may be important for the morphology and function of ciliated sensory neurons. However, it remains unclear whether these phenomena may be a consequence of the experimental system (ciliary protein overexpression); additionally, the link between EV uptake by glia and maintenance of neuronal structure and function is not convincingly established.

(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 substantially advances our understanding of why, when, and how wild birds use daily torpor as an energetic strategy. A technically challenging combination of carefully controlled experiments on temporarily captive wild birds along with frequent respiratory measurements and whole-body composition measurements was key to making this advance.

(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 has discovered deubiquitinase USP36 as the enzyme that processes FAU, a ribosomal protein precursor comprised of a fusion between ubiquitin-like protein FUBI and the ribosomal protein eS30. This is an important advance because correct processing is crucial for biogenesis of the 40S ribosomal subunit. Knowing the identity of the processing enzyme now opens this step in ribosome biogenesis to molecular and mechanistic analysis.

(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 is of interest to neuroscientists and psychologists working on perceptual decision-making and metacognition. Using a novel task varying the timing of covert decisions, together with sophisticated computational modelling, allowed identifying neural correlates of latent states related to confidence. The conclusions are in line with other papers identifying a dissociation between brain activity supporting performance and confidence, but provide a novel lens through which to understand these differences by focusing on confidence noise. An open issue is how to interpret conclusions about neural correlates of deviations from an ideal-observer model.

(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 rigorous and clearly written paper that provides quantitative data for the scope of intracellular signalling by ASIC channels. These channels are involved in pain signalling and other processes, and apparently can couple to intracellular pathways independent of ion flow. Here the authors measure the movements of the unstructured intracellular parts of ASIC using fluorescence spectroscopy coupled to functional measurements.

(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, #2, and #3 agreed to share their names with the authors.)

Evaluation Summary:

This paper is a very valuable contribution to paleoanthropology especially to those who study the evolution of human posture and locomotion. Overall, the quality of some of the fossils is unusually high for this chronology, and the data are properly presented and analysed. However, the authors should be more cautious in their interpretation of the data which does not fully support their 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This work clearly demonstrates an important role for two specific sodium-permeable ion channels for maintaining the pacemaker-like firing of midbrain dopamine neurons. These neurons have a key role in motivation, reinforcement and locomotion, and have been implicated in Parkinson's disease and multiple neuropsychiatric disorders. The authors also find that the regular firing of these cells is robustly maintained even when one of the two channels is knocked out, through upregulation of the level of the other channel.

(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:

The identification of p130 as a substrate of cyclin F adds a new level of understanding about the role of this ubiquitin ligase in cell cycle control. While much of the data are string and of interest, several concerns need to be addressed with the inclusion of new experimental data. This work will be of interest to researchers in the fields of cell cycle and cancer.

(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 paper provides further evidence for hemispheric asymmetry in the cortical control of manual actions based on intracranial (ECoG) recordings in human participants. Specifically, based a linear encoding model, the authors argue that movement encoding is more bilateral in the left hemisphere than the right hemisphere. The paper is well-written and the analyses are largely appropriate for addressing the primary hypothesis, though it would be helpful to detail the variability of electrode placement across individuals (which arises for the clinical intervention being undertaken) and incorporate this variability into the statistical analysis. Given the novelty of this type of human data and the well established question being addressed, this paper will be of interest to both basic and clinical researchers in motor 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 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript uses viral tracing to identify interneurons, throughout the spinal cord, which synapse onto motoneurons innervating pairs of flexor and extensor hindlimb muscles. Importantly, the data identifies single premotor interneurons which travel to, and presumably regulate the activity of, multiple motor pools. It is possible that these premotor neurons are involved in regulating muscle stiffness across a joint.

(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:

It has long been known that nerves regulate the early formation of the blastema during limb regeneration through the promotion of cell proliferation. The manuscript by Wells-Enright et al. provides an interesting new role for nerves during salamander limb regeneration by showing that nerves also determine how much tissue to regenerate. They demonstrate that increased nerve abundance makes bigger limbs while a decrease in nerve abundance generates smaller limbs. Size regulation of organs is a broadly interesting and clinically important problem, which is why this manuscript should be of interest to a large general audience.

(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 paper will be of great interest to scientists within the fields of developmental biology and evolution, as well as to researchers that generally use the sea urchin as a model system or those employing single-cell mRNA-sequencing technology. The work provides a comprehensive analysis of the cell state specification of a whole deuterostome organism and proof of principle of the use of single-cell sequencing to identity deep homologies of cell type.

(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, #2, and #3 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript studies the alignment of malaria parasites (merozoites) at the surface of red blood cells (RBCs), a key element of their reproduction cycle during the blood stage of the disease. Building on a computational model the authors developed previously, which incorporates the stochastic nature of RBC deformations and adhesive bonds between the merozoite and RBC, it is demonstrated that parasite shape plays a key role in its alignment dynamics. In particular, the authors shed new light on the egg-like shape typically observed in Plasmodium merozoites, which has important implications for how effectively the parasite can survive and multiply.

(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 strong manuscript due to its sophisticated behavioral analysis and modeling of behavioral output. The system and results provide a framework for future genetic analysis examining the biological basis of sensory behaviors.

(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 manuscript develops new software tools to analyze and classify single cells with high throughput based on single cell phenotyping using an existing imaging system. The authors show that tissues can be reproducibly decomposed into clusters of cells based on their feature space and that cell composition dynamics can be reliably detected. The main impact is to make single cell phenotyping more tractable, including for samples and organisms for which sequencing-based or fluorescent-labeling-based approaches are not readily available. Applicability was demonstrated in two research model organisms, zebrafish and freshwater snail.

(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.)