Evaluated articles

Evaluation summary

Ribonucleotide reductases (RNRs) have fascinated biologists and chemists, as these enzymes catalyze the conversion of ribonucleotides (NDPs or NTPs) to deoxynucleotides (dNDP or dNTPs), which are essential for DNA biosynthesis in all organisms. Given this role, they have been postulated to be the link in the transition from an RNA/protein to a DNA world. In addition, RNRs use an array of protein, metal-based, and nucleotide radicals for the reaction they catalyze. This paper creatively combines two methods of analysis to propose a new evolutionary model for the diversification observed for the RNR family into the three classes: I, II and III. The work is of interest to students of molecular evolution, RNRs and colleagues interested in the origin of life.

(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 role of satellite glial cells in the sympathetic nervous system has not been extensively investigated. Using targeted ablation of SGCs, the authors demonstrate that satellite glia has a profound effect on neuronal activity and the survival of sympathetic neurons. The peripheral sympathetic system is responsible for a wide spectrum of activities, including blood flow, heart rate, respiration, and digestion.

(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:

Kikumoto and colleagues explore the question of how stimulus- and response-related mental representations are stored and selected in working memory. The authors use a combination of decoding and representational similarity analysis on EEG data to provide evidence for conjunctive representations of action plans. This work would potentially be of great interest to readers in the field of working memory, motor preparation, and selective attention.

(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 presents an exploitation/exploration paradigm using a model-based approach in 18 patients treated with GPi DBS for Tourette's syndrome. Their main observation is that despite DBS (used as a proxy of GPi inhibition) doesn't have any effect on the overall performance of the subjects, it has a significant effect on the probability of exploration. This work will be interesting for scientists working in fundamental and clinical neurosciences.

(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 highly innovative study, the authors use combinatorial gene expression analysis to study the development of the gill arch of the little skate. This process depends on Shh and Fgf ligand-derived endodermal cells at the endoderm-ectoderm junction, providing insight into not only the fundamental developmental mechanisms regulating brachial arch formation in cartilaginous fishes, but also highlighting a unique relationship between inhibition of Wnt and Hedgehog signaling pathways in the context of early appendage development. The work will be of interest to developmental biologists and colleagues studying Wnt and Hedgehog 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. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This work is valuable for those who study how diet and metabolism impact neurological function, specifically learning and memory since it investigates the impact of high-fat diet intake during the preadolescent period on memory performances. The data convincingly showed the possibility to reverse memory deficits related to obesity by manipulating selected hippocampal circuits. The claims would benefit from additional controls and analyses.

(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, of interest to both basic scientists and clinicians, addresses the clinically important condition of reduced muscle mass in human chronic liver disease. It seeks causative mechanisms under these conditions. It uses in vivo and in vitro techniques to draw associations between bile acid concentrations and muscle disease. They implicate a specific bile acid for the first time.

(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 derivation of cardiomyocytes from the first and second heart fields is a well-studied phenomenon in animal models, however, due to ethical concerns, has not been studied in human heart development. The authors utilize hiPSC technology to demonstrate that it is the FHF and SHF that give rise to cardiomyocytes which is an important step in furthering our understanding of early human heart 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Detecting and quantifying balancing selection is a notoriously difficult challenge. In this study, the authors use both empirical analyses and simulations to characterize the amount of balancing selection in the human genome, focusing specifically on the contribution of polymorphic deletions. These results will be of interest to population and human geneticists. Although the presented evidence supports some degree of balancing selection among shared ancient polymorphisms, these findings primarily rely on the elimination of alternative explanations rather than a direct estimation of the extent of balancing selection. The conclusions are also based on simulations of a single demographic model without testing the robustness to other plausible model parameters.

(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 readers in the field of Alzheimer's disease, neurodegeneration, and single-cell omics. The identification of shared pathways across different cell types and ages is an important contribution to our understanding of APOE4 gene regulation in a cell type-specific manner. A combination of snRNAseq in APOE mouse models and human iPSC cells supports the key claims in the paper.

(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 will interest basic and clinical scientists and, potentially, device manufacturers interested in the regulation of heart rate in health and disease. A major control of the heart is from the nervous system originating in a neuronal cluster sitting outside the heart called the stellate ganglia. This study has identified the neural code associated with a healthy heart and describes how it changes in disease. Whether the change in code is cause or effect remains equivocal although normalising the code may have valued therapeutic benefit. The study opens the way for sophisticated mimicking of healthy neural code applied to a diseased heart as a potential electroceutical approach.

(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:

DNA double-strand breaks are a major threat to genome stability. In this study, the roles of two DNA repair proteins, Brc-1 and Smc-5, are investigated in C. elegans meiotic cells, to investigate the DSB repair pathways using the homolog or the sister chromatid as template . The results highlight a regulatory role of Brc-1 and Smc-5 as repressors of repair with the sister chromatid. The experiments are generally well executed, and the findings will be of interest to the DNA repair and C. elegans meiosis communities.

(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 study presented in this manuscript is of interest to cartilage biologists studying the mechanisms of chondrocyte differentiation. The authors investigated transcriptomic profiles of hESC-derived articular and growth plate chondrocytes. To characterize the regulatory landscapes with respective transcriptomes, they mapped chromatin accessibility in hESC derived chondrocyte lineages and mouse embryonic chondrocytes using ATAC-sequencing and revealed lineage-specific gene regulatory networks. They further validated functional interactions of two transcription factors, Runx2 and RELA, with their predicted genomic targets. This study could help us understand chondrocyte 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 study presents novel experimental data from a mutant mouse model lacking microglia (Pu.1-/- mouse line), indicating that these cells have an important role in the embryonic establishment of critical neural circuits in the brainstem generating breathing motor behavior in mice. This paper is of interest to scientists within the field of microglia as well as respiratory neurobiology as it provides original key information about a new role of microglia in the embryonic development of respiratory circuits. Overall, the data are clearly presented and rigorous. Some of the conclusions should be toned down as the data in another microglia depletion model do not support some claims of the paper.

(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:

Apoptotic regulators have long been known to often be expressed in pairs of pro- and anti-apoptotic isoforms. This demonstration of how a program of these splicing changes contributes to immune responses adds an important new understanding of both apoptosis and T cell 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper's central findings - that wtf genes are old, rapidly evolving, and often meiotic drivers - are important and of broad interest to evolutionary biologists and geneticists. The study's main claims are supported by convincing evidence from comparative genomic data, phylogenetic analyses, and functional experiments. However, support for the verbal model of wtf persistence is currently incomplete.

(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 applies hybrid-capture sequencing for coronavirus (CoV) surveillance in bats. Given that bats are a major reservoir for animal-to-human virus spillover events, which have caused several major epidemics/pandemics, this is a very important field of research. The reported hybrid-capture method shows some clear advantages over amplicon-based viral sequencing, which is the established standard in the field. This new approach has clear merits that are well supported by the data presented and is likely to become an important tool in viral surveillance programs that ultimately aim to predict/prevent/prepare for future pandemics. The work will be of interest to microbiologists, particularly those studying viruses or interested in genomics surveillance.

(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:

The current manuscript presents a computational model of numerosity estimation. The model relies on center-surround contrast filters at different spatial scales with divisive normalization between their responses. Using dot arrays as visual stimuli, it is shown that the summed normalized responses of the filters are sensitive to numerosity and insensitive to the low-level visual features of dot size and spacing. Importantly, the model provides an explanation of various spatial and temporal illusions in visual numerosity perception.

(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:

The human small heat shock protein (sHSP) HSPB5 is an ATP-independent molecular chaperone involved in maintaining protein homeostasis. This manuscript reports on dynamic interactions between the disordered N-terminal region (NTR) and the structured alpha-crystallin domain (ACD) in HSPB5 oligomers. The authors show that two mutations, associated with early cataract and myopathy development, disrupt the interaction of the ACD core with the unfolded NTRs and generate a much more dynamic and hyperactive version of the chaperone. These findings will be of interest to colleagues studying molecular chaperones and their implications for disease in humans.

(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 researchers working in the area of lower urinary tract dysfunction. It describes a novel method to reliably study bladder function; the approach allows for monitoring bladder filling and emptying in freely moving, non-anaesthetized animals without the need for catheter implantation. This work has optimized a machine learning algorithm for defining the outline of the urinary bladder border from fluoroscopic images of mice that received subcutaneous injections of iodinated radiocontrast media. The advantage is that with images taken at 30 images/second and with monitoring bladder dynamics requiring hours-long observation periods, this very large number of generated images no longer requires manual 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. Reviewer #1 agreed to share their name with the authors.)