Evaluated articles

Evaluation Summary:

The authors have discovered that the transcription factor Zfp335 is an important regulator of early T cell development in the thymus. This paper will be of interest to scientists within the field of T cell development. The approaches used are thoughtful and rigorous and the key claims are supported by the data. Whether or not Zfp335 specifically controls beta-selection via the gene targets described requires additional experimentation.

(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 manuscript by Yu et al. captures the transcriptional heterogeneity of mouse POMC neurons across hypothalamic development. This study unifies multiple other observations about the role for other neuron al cell types that express POMC transiently during development. The paper is an important resource understanding of the diversity of POMC neuron classes and their relationship to other cell types in the arcuate 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. The reviewers remained anonymous to the authors.)

Evaluation summary

This manuscript is of broad interest to the DNA-repair and structural biology field. The paper describes new insights into the interaction between ATM and Nsb1, proteins central to repairing DNA double-strand breaks in humans. Overall, the structural cryo-electron microscopy data is solid and the data well analyzed and presented with key claims directly related to and supporting previous known 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The study reports the development of high-throughput droplet digital PCR to detect Plasmodium falciparum parasites carrying pfhrp2 and pfhrp3 gene deletions. These mutations usually cause false-negative RDT results on malaria tests. Although there are several PCR-based detection methods already available, the assay is useful as an alternative, particularly in countries and settings where droplet digital PCR is routinely used. The strength lies in its capability to detect hrp2 and hrp3 deletions in samples with multiclonal (more than one clone) infections. This has the potential to assist in surveillance for pfhrp2/3 deletions programs where RDTs designed to detect HRP2 are the primary test leading to false negative results, particularly in medium to high transmission settings. The study will be of interest to those studying infectious diseases.

(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 manuscript will be of interest for researchers interested in DNA repair and transcriptional regulation. The authors provide a series of well-executed and designed high-resolution sequencing data demonstrating that transcription factor (TF) binding perturbs alkylation base damage formation as well as inhibits its repair via base excision repair (BER) at TF binding sites. Moreover, they demonstrate differences between nucleotide excision repair and BER at TF binding sites that are consistent with the different repair mechanism of these two pathways. These results should have an important and timely impact on the 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 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of interest to neuroscientists, particularly those studying defensive behaviors. The authors provide novel insights into the mechanisms by which the brain computes contextual information associated with innate threats in mice. The experimental approach and data analysis are mostly adequate and the study provides the first causal evidence of a hippocampus-anterior hypothalamic pathway mediating spatial fear memory of ethological threats. The implementation of more robust statistical tests, as well as more detailed Methods and Discussion sections should serve to strengthen an already elegant study.

(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:

This study reveals that anesthesia-induced burst suppression's spatial patterns differ across humans, macaques, marmosets, and rats. Given that burst suppression is considered a hallmark of unconscious states, these findings are potentially important for us to understand the evolution of the neural correlates of consciousness. In addition, a novel, purely MR-based method is presented to identify and map burst suppression, which may have relevance in both clinical and experimental studies.

(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 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper addresses an important problem in control of episodic memory. This paper develops a computationally-based proposal about how semantic, working memory, and episodic memory systems might learn to interact so that stored episodic memories can optimally contribute to reconstruction of semantic memory for event sequences. This is an understudied area and this present work can make a major theoretical contribution to this domain with new predictions. The reviewers were positive about the contribution.

(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 authors applied original approaches to explore the evolution of transcription factors following duplication and subsequent divergence among duplicates. This paper should generate broad interest among evolutionary biologists as it addresses the long-standing question of how newly evolved transcription factors acquire new binding specificity. By combining genome editing with high-precision DNA binding profiling, this study provides extensive in vivo data showing how the binding profiles of transcription factor paralog pairs diverge.

(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:

LIS1 is a key regulator of the microtubule motor cytoplasmic dynein. Here the authors use yeast proteins and streptavidin-coated grids to solve the first high-resolution (3.1Å) structure of the dynein-Lis1 complex. The two beta-propellors in a Lis1 dimer make contact with different sites on a single dynein motor domain. Mutagenesis shows both sites are important for yeast and human dynein and uncover how they modulate motor 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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

Are enzymes found in organisms that optimally grow at colder temperatures are more active than the same enzymes found in organisms that optimally grow at warmer temperatures? Here, an assessment of the catalytic constants for approximately 2200 enzymes (obtained from the BRENDA database) showed no correlation between the relative catalytic activity and the optimum growth temperature. Further support for this conclusion was obtained from the measurement of the catalytic constant from a selection of ketosteroid isomerases from organisms that optimally grow between 15 and 46 degrees centigrade. These are interesting results, although the significance with respect to earlier studies has not been clearly explained.

(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 measures the transmission of SARS-CoV-2 lineages in Canada and the rate at which lineages were imported into Canada from other countries during the first year of the pandemic. This information is critical for understanding basic SARS-CoV-2 evolution and epidemiology, but the impacts of sampling biases in space and time might weaken 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 paper will be of interest to neuroscientists interested in predictive coding and planning. It presents a novel analysis of hippocampal place cells during exploration of an open arena. It performs a comprehensive comparison of real and synthetic data to determine which encoding model best explains population activity in the hippocampus.

(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 report presents findings of broad interest to behavioral, systems, and cognitive neuroscientists. The combination of a complex behavioral paradigm and sophisticated modeling provides significant insight and a novel approach to studying higher cognition in primates. Key clarifications are needed that have to do with better justification for the modeling strategy, selective comparisons within the data, and a more thorough consideration that subjects may employ a more passive strategy.

(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 addresses the question of why invertebrates use innexins and vertebrates connexins to form gap junctions. The authors survey genomic data across animal diversity to search for innexins and connexins and analyse the distribution of glycosylation sites in the extracellular loops of these proteins. The reported data support the hypothesis that connexins replaced innexins in chordate gap junctions due to an evolutionary bottle neck. Overall, the data were properly analyzed, but could be improved with respect to the sequence data for some phyla and the discussion from the results obtained.

(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:

A well written and informative study that uses scRNA-seq to examine Th2 biology in worm infections. It offers a unique angle for better defining Th2 heterogeneity and differentiation 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:

Bergeron et al show that mutation rate independently estimated by several teams with a same pedigree dataset can be different due the methods and approaches used to identify de novo mutations. This result is of primary importance because it shows the necessity to have standard mutation identification method and the difficulties to compare mutation rates from different studies.

(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:

To establish a mouse model for the SARS-CoV-2 infection, Gawish and colleagues performed serial passage of a human virus isolate in mice. They show that the mouse-adapted SARS-CoV-2 variant remains dependent on ACE2 for efficient infection and recapitulates some clinical characteristics of COVID-19. In addition, they demonstrate that inhalation of recombinant ACE2 protected mice from mouse COVID-19 suggesting this this model will be useful for the testing of antiviral agents.

(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:

Using coarse-grained simulations, machine learning analysis and Bayesian inference modeling, the authors explored features that dictate the location and kinetics of electroporation in complex lipid membranes. The resulting understanding and modeling will lead to an effective multi-scale approach for predicting the kinetics of electroporation and guiding the design of experimental protocols for inducing electroporation in broad applications such as tumor treatment, gene therapy and vaccination against 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 #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This article provides insight into how Astyanax mexicanus cavefish may have adapted to the hypoxic waters present in the cave environment. How the extreme environmental pressure of low oxygen has shaped cavefish evolution has been understudied compared to other pressures like absence of light or low nutrients. This is the first study to look for changes in early cavefish development that may provide hypoxia tolerance. The claims that cavefish have expanded erythrocyte development and increased hypoxia gene expression are strongly supported by the data. Demonstrating that these traits are adaptive and provide hypoxia tolerance requires further assessment of the current results and would be strengthened by additional experiments. Overall, this work is an important first step in understanding the evolution of hypoxia tolerance in A. mexicanus cavefish.

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