Evaluated articles

Evaluation Summary:

ESCRT-III is a conserved hetero-oligomeric membrane remodeling machine known to impact a number of cellular phenomena, yet mechanistic details of its function have remained enigmatic. This work identifies critical inter-subunit contact sites critical for ESCRT-III assembly and 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:

Reviewers value the development and characterization of a bladder-on-chip infection model for recapitulating the multiples factors involved in UPEC driven UTIs. Notably, it consists of human bladder epithelial cells, bladder microvascular endothelial cells, neutrophils and urine that are also subjected to mechanical changes mimicking those occurring during bladder filling and micturition. This model is a lot more complex than in vitro tissue culture models and more amenable to analysis such as imaging than animal models and therefore constitute a distinct advance for in vitro modeling of UTI that has potential to reveal key aspects of UTIs and reasons for the difficulty to clear these infections with antibiotics.

(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 reports that Volatile anesthetics VA induce a rapid depletion of circulating ß-HB and the induction of hypoglycemia by VA in neonates, but not in adults. The phenomenon is very interesting and robust, however it has already been described. Whats new here is that through a metabolomics analysis they demonstrate a role of ACC and CPT1 in this phenomenon.

(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 experimental system characterized in this paper opens up new avenues for studying mechanisms of retinal patterning and morphogenesis. The data presented make a compelling case for the emergence of complex multicellular structures upon re-aggregation of embryonic teleost cells, but open questions remain regarding the basic underlying principles.

(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 is of broad interest to those performing multiplexed genome engineering and related applications with CRISPR Cas12a technologies. While the proposed use of synSeparators is promising, the paper would benefit from further investigation of the mechanism by which synSeparators function to promote Cas12a activity. Additional data would be required to support the current conclusions regarding 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 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

In this manuscript, Lawrence et al. investigate the direct effects of the microtubule-associated protein, SSNA1, on microtubule dynamics and damage using purified proteins and TIRF microscopy. The authors conclude that SSNA1 is a microtubule stabilizing protein and a sensor of microtubule damage. This paper is of high interest to scientists within the field of microtubule mechanics and of broad interest to scientists studying cilia, cell division and neuronal development.

(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:

In this study, Pulgar et al. describe an interesting phenomenon addressing organ integrity in a unique example of collective cell migration. The group focused on the migration of the dorsal forunner cells (DFC), which will constitute the left-right organizer of the zebrafish. The authors show that DFCs retain apical contacts stemming from incomplete delamination and drag detached DFCs to their final destination. The study opens a number of exciting new questions related to the mechanism underlying the 'safeguards' process and the mechanism of coordination between migration and regulation of attachment.

(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 is one of the first studies to investigate sex-biased gene expresion in a broad phylogenetic context, and the first in a plant genus. The findings go against the classical view that sex-biased gene expression is driven by sex-specific selection for sexual dimorphism, and instead suggests that sex-bias preverentially evolved in genes that already had the highest expression variance to begin with. It will broadly appeal to researchers interested in the evolution of sexual dimorphism.

(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:

Frey et al. describe a convolutional neural network capable of extracting behavioral correlates from wide-band LFP recordings or even lower-frequency imaging data. The analysis program described by the authors provides a rapid "first pass" analysis using raw, unprocessed data to generate hypotheses that can be tested later with conventional in-depth analyses. This approach is of real value to the community, particularly as it becomes more commonplace for labs to acquire multi-site in vivo recordings.

(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 focuses on the formation of adaptor protein complexes at adhesion sites and their links to in vitro membrane ruffling and cell movement. Specifically, the authors study the role of the adaptor BCAR3 protein which is regulated by post-translational mechanisms (ubiquitin degradation and tyrosine phosphorylation). The authors propose a "co-regulatory" model whereby the recruitment of BCAR3 to adhesions acts to modulate p130Cas tyrosine phosphorylation and cell migration. This manuscript would be of particular interest to cell and cancer biologists interested in the molecular regulation of 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This work evaluates the strength of the evidence that human sexual dimorphism is the product of sexual selection. As a meta-analysis of studies that connect various measures of masculinity to various measures of reproductive success, this paper represents a synthesis of what this vast literature can show thus far. The work will be of general interest to evolutionary social scientists from a variety of disciplines, and it does a good job of clearly and concisely presenting the current state of sexual selection research on human males. The data are well presented, but the interpretation of the results is currently limited by some gaps in the theoretical framework guiding the 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. Reviewers #1-4 agreed to share their names with the authors.)

Evaluation Summary:

This study provides identification of different subpopulations of blood cells and gives new insights in putative hemocyte lineage relationships by single cell RNA sequencing. The main conclusions are fairly well supported by the data and this manuscript will be of high interest to crustacean immunologists and readers in the field of aquaculture.

(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 authors use a variety of complementary approaches to visualize and characterize events in the first half of the HIV life cycle, with some overlap between the latter studies and the recent (and cited) Zila et al. bioRxiv paper from some of the same authors. The data are generally of high quality, and many findings are in line with recent field advances indicating that reverse transcription completes in the nucleus, that intact/nearly intact cores are imported into the nucleus, and that nuclear uncoating likely occurs immediately prior to integration. The results provide the best evidence to date that intact capsids can enter the nucleus of target cells during infection, and will generally be of interest to the field, although the impact is diminished somewhat by similar recent publications from a number of other groups (including one case that used nearly identical labeling methods to follow viral complexes during infection). Issues that should be addressed include missing controls in some cases, some examples of over-interpretation and uneven citation, and the need for additional images to help bolster some of the claims. Strengths of the study include the rigorous characterization of infection using sophisticated imaging methods and, most importantly, the use of CLEM-ET to visualize viral capsids in the nucleus.

(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 manuscript demonstrated the effectiveness of combined activation of Atoh1 and Ikzf2 in converting adult supporting cells to outer hair cell (OHC)-like cells in a mouse model, in which the OHCs were selectively ablated with diphtheria toxin. The authors showed that while the number of regenerated hair cells was low and there was no functional recovery based on ABR, these OHC-like cells do express Prestin and exhibit a genetic profile that resembles nascent hair cells. This paper will be of great interest to researchers interested in hearing restoration, as well as regenerative 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 helps explain some enduring mysteries about why certain activating mutations appear in the KRAS gene more frequently than others. This paper provides experimental support for an emerging concept within the Ras field that there is a sweet-spot of Ras signal strength that promotes tumorigenesis and that this explains why different mutations are observed in different contexts. The experiments are sound and the conclusions are fair. Given that certain KRAS mutations may be more amenable to therapeutic interventions than others, it is important to understand the basis for mutational tropism, and this work provides strong in vivo evidence that addresses this issue.

(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:

In this paper Sun and colleagues aimed to demonstrate the feasibility of using CRISPR-based gene editing techniques applied to tissue-derived human fetal lung organoids. While previous studies have used CRISPR-Cas9 to perform knock-in or knock-out studies in organoids (such as intestinal, hepatic or tumor organoids), this is the first report to apply these tools to a tissue-derived lung organoid model. A major strength of this report is the additional use of CRISPRi and CRISPRa technologies. The work is well done, clearly presented and makes an important contribution to the literature.

(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 interesting phylogenetic analysis of a mumps outbreak in Washington will be of interest to a wide audience, especially those working at the intersection of pathogen genomics and public health. An array of classic and novel phylogenetic approaches supports the conclusions that mumps was introduced several times in Washington during the outbreak, and that the Washington Marshallese community was particularly at risk of mumps infection and transmission despite high vaccination coverage. Inferences regarding the role of age and vaccination status are however less conclusive given the small sample size. Consultation with a community health advocate from the affected communities helps contextualize 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:

The paper "Regional sequencing collaboration reveals persistence of the T12 Vibrio cholerae O1 lineage in West Africa" presents results from sequencing and analyzing 46 Vibrio cholerae whole genome sequence data. The paper presents findings from a region with little genomic surveillance, and as such these data are valuable. While the analysis doesn't provide much novelty in terms of understanding cholera transmission, the study was conducted in the context of a regional training, and as such adds value as a potential model for regionally coordinated genomic surveillance efforts in areas where surveillance is limited. However even though it seems that the authors aim to present this as a surveillance model, the current focus of the paper is on the somewhat limited inference made about transmission.

(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 provides the basis for further discussion about the perceived inequities in NIH funding based on race. The strengths of this manuscript are the detailed breakdown of the available data in order to evaluate for biases, the availability of data for multiple years (2011-2015) and the consideration of alternate explanations (e.g. new applications vs resubmissions; single vs multi PI). With that said, given their conclusion that Institute (IC) assignment was the main determinant of funding rates, the approach for IC assignment should have been discussed. Other issues relate to the complexity of statistical analyses and a lack of clarity on confounding issues towards firm 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 #1 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

It is difficult to overestimate the importance of this paper. The full connectome of the Drosophila central complex is both the beginning and the end of an era. It provides the first comprehensive dataset of arguably the most enigmatic brain region in the insect brain. This endeavor has generated ground truth data for years of functional work on the neural circuits the connectome outlines and constitutes an unparalleled foundation for exploring the structure function relations in nervous systems in general. While significantly going beyond models of central-complex function that existed previously, the authors have to be much credited for incorporating huge amounts of existing knowledge and data into their interpretations, not only work from Drosophila, but also from many other insects. This effort makes this paper not only an invaluable resource on the connectome of the Drosophila central complex, but also a most comprehensive review on the current state of the art in central-complex research. This unifying approach of the paper clearly marks a reset of central-complex research, essentially providing a starting point of hundreds of new lines of enquiry, probably for decades to come.

(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.)