Evaluated articles

Evaluation Summary:

This study will be of interest to scientists studying neuroinflammation and searching for potential therapeutic targets. The findings here have revealed the effects of an anti-inflammatory cytokine, human IL-37 (hIL-37), in the central nervous system of mice. The data support the conclusions within the current mouse models. Since hIL-37 is not naturally expressed in mice, more evidence related to human cells or tissues would strengthen the physiological significance.

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:

Rabies-mediated monosynaptic retrograde tracing is a powerful method to characterize the connectivity of neural circuits. The CVS-N2c strain of rabies virus shows significantly higher efficiency of transsynaptic spread and less toxicity than the more commonly used SAD B19 strain but has been limited in use by an arduous and lengthy packaging process and low resultant titers. Here, Sumser et al. present a method that significantly speeds up the production process while reducing off-target expression. They also introduce a suite of novel reagents (34 novel plasmids) for monosynaptic tracing with the CVS-N2c strain that they commendably, have already deposited with Addgene. The work is an important advance that will reinvigorate rabies-mediated circuit tracing.

(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:

Cohesin is an evolutionarily conserved protein complex that plays essential roles in mitotic chromosome structure and function. Previous studies suggest that multiple activities of cohesin are required only prior to the onset of chromosome segregation. Using a Mcd1-AID and a Mcd1-TEV to either degrade or cleave cohesin's kleisin subunit Mcd1 of the yeast Saccharomyces cerevisiae, this study shows that cohesion plays also a role in anaphase organizing the centromeric regions, providing new evidence that cohesin function is critical for chromosome structure and segregation during and after the onset of chromosome segregation. The work is of relevance for students of chromosome biology and cell division.

(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:

Results from observational studies examining an association between the antihypertensive drugs and the risk of breast cancer reported inconsistent findings. This study uses a two-sample Mendelian randomization approach (MR), which overcomes the limitation of observational studies by using genetic variants as a proxy for modifiable exposures, to investigate the relationship between the use of antihypertensive medication and breast cancer risk. Using publicly available data and including a comprehensive assessment of antihypertensive drugs, the authors identified two SNPs that were associated with breast cancer risk. While the findings suggest that antihypertensive medication use may be associated with breast cancer risk, there are some methodological issues that need to be addressed.

(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:

FLT3 (Fms Related Receptor Tyrosine Kinase 3) activation occurs in a subset of acute myeloid leukemia (AML) cases and is associated with poor prognosis. This work is focused on the mechanisms of resistance to FLT3 inhibitors in AML. The authors show that the combination of the FLT3 inhibitor and an mTORC1 inhibitor reduces tumor burden and prevents relapse in FLT3 mutant AML. This paper is of interest in scientists and physicians investigating AML as well as scientists studying signaling pathways.

(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:

Overall, this study will make significant contributions to developmental neuroscience and vision science as they attempt to study how prenatal and postnatal maturation influence structural-functional measurements in the early and high-level visual cortex. These results will be of broad interest as it is a novel attempt to study processes that might be innate or genetically wired and those that emerge due to worldly experiences within the sensory systems. The authors are addressing an important and timely question based on a large and impressive infant database.

(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 demonstrates that artificial neural networks can be used to accurately predict the responses of biologically-detailed neuron models to synaptic inputs, and hence to approximate the behaviour of networks of such neurons. This study potentially opens the door to massively reduced simulation times for biologically-detailed neuronal network simulations without recourse to supercomputers and hence will be of broad interest to computational neuroscientists.

(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 describes novel insights into the potential function of innexin proteins, which are electrical synapse-forming proteins with often quite enigmatic in vivo functions. The authors describe here potential functions in synapse tiling. The paper should be of interest to researchers with interests in molecular mechanisms governing nervous system 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 paper the authors report an updated theoretical model describing in mathematical terms how the Hsf1 transcription factor is activated in yeast in response to heat shock, and demonstrate that rather than denatured mature proteins, Hsf1 activation involves newly synthesized proteins that sequester the Hsp70 chaperone away from the inactive Hsp70/Hsf1 complex, releasing active Hsf1. They also describe a general role for the Sis1 co-chaperone in maintaining the fitness of yeast cells under stress conditions, such as heat shock, that is independent of regulation of Hsf1.

(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 name with the authors.)

Evaluation Summary:

The authors bioinformatically analyze previous scRNA-seq datasets of the developing mouse soft palate to identify differential signaling pathway activities in the heterogeneous palatal mesenchyme. Identifying TGF-beta signaling pathway activity with the perimysial cells, they hypothesize and test whether TGF-beta signaling in the perimysial cells might regulate palatal muscle formation. This paper will be of high interest to developmental biologists interested in the molecular regulation of tissue interactions that occur during mammalian palate morphogenesis.

(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.)

eLife assessment

This important study provides a quantitative characterization and understanding of firing collective patterns in P. Carolinus fireflies. The work significantly contributes to fill the gap between observations and mechanistic models, with convincing experimental evidence and solid theoretical modeling. This work will be of interest to readers curious about collective behavior, biological rhythms, and models of synchronized oscillations.

Evaluation Summary:

This study provides insight into the identity of the sodium channel controlling excitability in proprioceptors. Using pharmacology, gene KO, behavior, and histology, the authors show quite convincingly that NaV1.1 in sensory neurons is essential for normal motor behavior and contributes to proprioceptor excitability. The work has interesting implications for human subjects with inherited variants of Nav1.1.

(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:

Some children conceived by assisted reproductive technologies (ART) exhibit metabolic differences compared to those conceived naturally, and the causes are unknown. This work reveals possible explanations for the metabolic differences and provides opportunities to improve ART and prevent the differences. This is a valuable contribution and will be of special interest to practitioners of ART, as well as to developmental and reproductive biologists.

(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:

Boddé et al propose a new approach for species identification in the genus Anopheles. The approach uses an amplicon panel, a kmer-based similarity metric, and a variant auto-encoder to minimize issues of sequence alignment between divergent lineages. The authors provide strong evidence that their approach works well for most samples. The work will be of potential interest to practitioners in the field of parasite carrying mosquitoes.

(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:

Nutrition profoundly affects neural development. The Uemura lab previously reported that C4da neurons elaborate complex dendrites when larvae grow on low-yeast diets, a phenomenon called neural sparing. In this current study, they define the molecular mechanism underlying the nutrition-mediated phenomenon and identify that the inter-organ Wingless/Ror/Akt pathway between the neuron and its adjacent muscles is necessary and sufficient to mediate dendrite overbranching in the low-yeast condition.

(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:

In this paper, the authors generate and analyze new genome and gene expression data to understand better the evolution of the white-throated sparrow supergene region, which contains 1000 genes and determines whether a bird has a tan or a white stripe. The study nicely illustrates how the cessation of recombination that results from a chromosomal inversion can become a source of evolutionary novelty. The lack of recombination can result in the accumulation of deleterious variation leading to degeneration, but it can also (as here) facilitate genomic diversification and adaptation. The results will be of interest to a broad array of researchers studying genome architecture and phenotypic diversity and evolution.

(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 study will be of interest to the large class of researchers who perform brain-behavior correlation analysis in the neuroimaging field, especially those related to neurodevelopment. The authors found that controlling for socioeconomic and maternal behavioral confounders, in addition to the usual demographic variables, generally attenuated such associations in ADHD using two independent large cohorts. The findings highlighted the importance of careful confounder selection and control for robust brain-behavior associations.

(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 extensive study dissects the different gene expression patterns in a large set of different human lower limb muscles. It is an extensive transcriptome study. Its potential importance is that it points out insights into their differing changes in particular muscle diseases associated with specific gene defects.

(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 helical shape of the bacterial pathogen Helicobacter pylori is important for its ability to colonize the human gut. Building on previous work identifying a complex of proteins required for generating helicity, this study focuses on the molecular mechanisms by which this complex modulates cell shape. Based on results from genetic, cytological, and pull-down experiments, the authors propose that one member of the complex, the bactofilin CcmA, interacts with two other complex members to generate helicity through a combination of cell wall synthesis and degradation. While data is supportive of this idea, the conclusions of the study require additional experimental support to rule out competing models.

(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, the authors focus on the fungus B. bassiana, which is resistant to the toxin cyclosporine A. Through a mutant screen, the authors identify the key gene that mediates the sequestration of the toxin in vacuoles. They further show that this gene can be transferred to a distinct fungus and also to plants to protect against a toxin-producing fungal pathogen. Therefore, this work may lead to novel disease control strategies against fungal pathogens.

(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.)