Evaluated articles

Evaluation Summary:

This paper is interesting, timely and important because it presents a way to understand the transmission potential of a virus even when there are very few local cases. This has a high public health communication and preparedness value. The paper is clearly written, and the results fit with the known epidemiology of the various outbreaks that occurred in Australia in 2020. The paper is likely to be of broad interest within and outside the field of epidemiological modelling.

(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 name with the authors.)

Evaluation Summary:

The manuscript by Routledge et al. describes the role of Reggie-1/Flottilin2 in the formation of filopodia-like membrane protrusions called cytonemes and which were shown to be conserved between gastric cancer cells and Zebrafish. Authors demonstrate that Flot2 is present on the cytoneme along with Wnt3 in gastric cancer and with Wnt8a in Zebrafish. Furthermore, Flot2 is also present with Ror2 on the cytoneme and together they are believed to modulate cytoneme formation. This study extended the previous studies and provides new details about regulatory events controlling a cell biological process that will be of interest to those in the Wnt and cytoneme fields.

(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:

The neural correlates of voluntary action is one of the most intriguing questions in neuroscience, but studying it at laboratory settings is incredibly difficult. Here, the authors have used an impressive range of methods and analyses approaches in mice to investigate the neural activity preceding voluntary action in mice. Using widefield calcium imaging in mice to study volition is novel and welcome but the great strength of this paper is its wide range of analyses approaches. There remains a question to what extent the findings reveal specific properties of 'voluntary action,'.

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 work investigated the mechanism of the cadherin-catenin F-actin catch bond interaction, a fundamental cell-cell adhesive structure that can be both dynamic and force-activated. Force measurements with purified protein components demonstrate that the catch bond results from a force-dependent switch of the actin-binding domain of αE-catenin between a five-helix bundle and a four-helix bundle bound on F-actin. The findings are interesting and well supported by experimental data, and will be interesting to the broader field of cytoskeleton function and functional structural biology.

(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 work by Cheng et al evaluates the contribution of regulation of gene expression at the RNA and protein level by leveraging copy number variations in a large cohort of cancer samples. Importantly they find that there is rarely compensatory regulation at the RNA and protein level together, but depending on the gene, expression is either compensated at one or the other. The paper is very intriguing and the findings are of interest to a broad readership.

(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 describes a biochemical analysis of the roles of Ub chain length on Ub-dependent segregase activity of yeast and human p97 and the role of UBX proteins on the disassembly of the CMG replicative helicase complex. The human p97 complex does not segregate substrates with shorter ubiquitin chains as efficiently as does the yeast complex but the human complex can be enhanced in vitro by 3 UBX proteins - FAF1, FAF2, and UBXN7. Cellular studies indicate a partial role for FAF1 and UBXN7 in cells. The paper would be strengthened by additional mechanistic understanding of how the UBX domain functions in activation of segregase activity and the contribution of this pathway in cells.

(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 can provide novel basic science insights into how brain responses at different frequencies signal sensory information. An analysis of intracranial recordings in 121 human participants shows that low-frequency local field potentials and high-frequency (>30 Hz) broadband activity in response to face stimuli have largely similar spatial, functional, and timing properties. However, it is essential to show that the two response types can be reliably disambiguated and to critically discuss the generalizability of the findings.

(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 paper studies how pheromone-sensing neurons of the vomeronasal organ establish and maintain cell identity. A role for a particular transcription factor, AP-2e, is investigated using targeted gene knockout and rescue, and observations reveal an unexpected plasticity in the cell identity of mature sensory neurons. This paper should be of broad interest to neuroscientists and cell biologists studying mechanisms of cell development and differentiation.

(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 work is potentially very important to dissect the immune repertoire of T/B cells, which is one of the most critical/difficult parts for the adaptive immune system to achieve antigen specificity. These conclusions and proposed methods will require additional experimental support and further validation in different disease conditions.

(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:

In this manuscript Nunes Santos et al. use a combination of computation and experimental methods to identify and characterize a cis-regulatory element that mediates expression of the quail Slow Myosin Heavy Chain III (SMyHC III) gene in the heart. The study contributes to our understanding of how genes can be expressed differentially in the atrial and ventricular chambers of the heart. The evidence for the newly-identified gene regulatory sequence, and its origin, in exclusively directing these gene expression differences could be stronger. This study is of potential interest to readers in the fields of developmental biology, evolution, gene regulation, and biology of repeats.

(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:

Wei- Jai et al., demonstrate the protein Human liver DnaJ-like protein (HLJ1) converts misfolded IL-12p35 homodimers to monomers in sepsis. This contributes to increased IL-12 activity, in macrophages which in turn leads to an increased production of IFN-gamma production and lethality in mice. This study suggests that HLJ1 plays an role in regulating IFN dependent mortality and future studies may determine a therapeutic role in blocking this protein.

(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 would be of interest to all researchers who work in understanding the mechanisms involved in podocyte slit diaphragm homeostasis and maintenance of the glomerular filtration barrier. The work provides substantial new insights into nephrin dynamics and the mechanisms of slit diaphragm maintenance. A series of compelling experiments depicted that dynamin-mediated endocytosis was involved in ectopic nephrin turnover and that flotillin-mediated turnover of nephrin occurred within the slit diaphragm was needed to maintain filter permeability in-vivo.

(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 name with the authors.)

Evaluation Summary:

This manuscript addresses a potential role for the box C/D Small Nucleolar Ribonucleoprotein complex at the intersection of mitochondrial homeostasis and cellular responses to infection and environmental stress in the context of the C. elegans system. The presented data can be explained in multiple ways and can serve as starting point for further research in this interesting and important area.

“(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:

In this study, the authors present a numerical model of ant raft shape dynamics. It is an interesting topic, the experimental movies are exciting, and the idea that ant rafts make protrusions is new. The goal seems to be to explain how local interactions can lead to the perpetual protrusions of the raft. Since the biological significance of the results has not been clarified, the paper is likely to be primarily interesting to engineers and experts on robotics.

(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 very clear paper, which will be of interest to scientists in the field of evolutionary biology, investigates the effect of population structure on the efficacy of selection on a single locus. The results are based on analytical computations and numerical simulations, conducted in a scientifically rigorous manner. Although the conclusions are currently limited, the paper could serve as a solid basis for a more ambitious investigation.

(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 is of interest to biochemists studying DNA replication and genome maintenance in eukaryotic cells. The work details a structure-function analysis of an interaction between two proteins that are critical for genome stability. A mutation that disrupts this interaction may have no adverse effects under unperturbed conditions but causes telomeric DNA damage when cells experience replication stress. However, the structural nature of the damage and cellular consequences are not sufficiently explored.

(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 reports a novel function of non-coding RNA miR-22 in the regulation of tumor-associated angiogenesis. The presented data suggest a possible link between microRNA and endothelial cell function. If the underlying mechanisms were further explored, this work would be interesting for people working on microRNA function in endothelial cells. Furthermore, considering the increasing interest of combination of anti-angiogenesis agents with anti-PD1 immunotherapy, this work may attract readers interested in immunology.

(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:

High-throughput approaches that accurately assess drug target vulberbility in Mycobacterium tuberculosis, the causative agent of tuberculosis, are urgently needed to develop new treatment options for this dreaded disease. This paper applies a CRISPRi based approach to investigate gene essentiality and vulnerability on a diverse set of 96 genes. While the key observations of the study support previous findings, the approach reported here is useful for identification and characterization of novel drug targets. The study will be of interest to microbiologists and those interested in diverse aspects of bacterial 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 paper provides an attempt to understand the crosstalk between to islet cell types during beta cell regeneration following partial pancreatectomy. It combines lineage tracing, single cell sequencing and light microscopy to describe islet cell heterogeneity and interactions in the regenerating mouse pancreas. The concept of protective signaling resulting from the direct interactions between beta and delta cells is compelling and would be of interest to scientists in the field of endocrine pancreas development and regeneration. However, the conclusions derived from the sequencing data require additional experimental support.

(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 investigates how deficiency in the RNA splicing factor SON impairs centriole assembly, which may underlie ciliopathy-like phenotypes in humans with SON mutations and is thus of interest to both cell biologists and clinicians. Using RNA-sequencing analysis and advanced imaging techniques the authors discover a large number of known and new SON splicing targets and attempt to identify those crucial for SON knockdown defects. However, knockdown of a subset of targets did not fully recapitulate SON depletion phenotypes and only led to the relatively vague conclusion that the observed centriole assembly defects were caused by impaired protein trafficking around the centrosome.

(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.)