Evaluated articles

Evaluation Summary:

The authors measure the three-dimensional organization within an epithelial cell monolayer and find that cell neighbors change frequently along the apicobasal axis. State-of-the-art image analysis convincingly justifies correlation, though not causation, between epithelial cell packing and nuclear position. With some stronger theoretical arguments to back up the claims made, this paper will be of interest to scientists studying tissue mechanics and packing of cells in epithelial tissues.

(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 is of interest in the field of comparative genomics as it provides novel genomic resources for the whale shark, which belongs to a group of vertebrates which has to date limited available genomic data. While the strength of this manuscript is the publication of a novel genomic resource, the importance of the conclusions and the broader impact remain unclear, particularly because the work on its own does not yet provide new insights into the biology of whale sharks.

(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 article, global kinome profiling using fibrolamellar carcinoma and melanoma cell line models was employed to identify key effectors of protein kinase A (PKA) oncogenic signaling, which is hyperactivated in these cancer types. Based on use of molecular and cellular biology assays, authors proposed a model whereby the oncogenic effects of PKA are at least in part mediated by Aurora Kinase A (AURKA)- and PIM2-dependent regulation of MYC family members, and provide evidence that cancers with constitutive activation of PKA may be sensitive to AURKA inhibitors. Overall, it was thought that this study is of broad interest inasmuch as it provides new insights into the molecular underpinnings of oncogenic PKA signaling, and suggests the potential of using AURKA inhibitors to target malignancies characterized by aberrant PKA activation. With stronger mechanistic data linking constitutive PKA signaling to activation of AURKA and PIM2 and MYC regulation and in vivo experiments to support the conclusions, this manuscript will be of interest to researchers in the fields of cancer research, therapeutics, signal transduction and molecular and 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript is of interest to microbiologists and protein biochemists who study biofilm formation, haem proteins, and cellular responses to extracellular oxidative stress. It proposes a mechanism for biofilm protection from reactive oxygen species (ROIs) through the examination of the Gram positive, Bacillus subtilis. The data support many of the conclusions of the paper and highlight the importance of cell surface-localized protein peroxidase activity for proper biofilm assembly in a model species. Further evidence is needed to fully support the proposed mechanisms.

(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 is a follow-up on an impactful behavioral study from the same team, characterizing age-related differences in how individuals use information about environmental regularities to guide memory encoding. This paper will be relevant to those interested in the neurodevelopment of reward learning, episodic memory, and memory-guided decision-making. The combination of a clever task and thorough data analysis make this an impactful paper, but future longitudinal studies will need to determine whether these findings reflect developmental changes or cohort effects.

(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:

One key question in evolutionary biology is how traits can be affected by spontaneous mutations. This relationship between traits and mutations influences the rate and direction in which traits evolve. Here, the authors map a set of mutations that affect the expression of a focal gene in yeast, and examine their individual effects and locations in the genome and in the regulatory network. The work is rigorous and the results are well presented. The findings will be of great interest for geneticists and evolutionary biologists interested in the evolution of gene expression and of complex traits. Additional analyses and discussions will strengthen the generalization of the conclusions.

Evaluation Summary:

This manuscript describes an improved approach (MGCA) to identify risk genes for human traits and diseases using data from genome wide association studies. The authors demonstrate the utility of their approach by analyzing data from patients with schizophrenia, and narrow in meaningful biological processes and potential drug repurposing candidates. This approach will facilitate gene prioritization from large genetic datasets for downstream applications such as functional 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper will be of interest to neuroscientists studying the navigation system, and in particular those who study the ability of animals to path integrate. This study proposes an elegant synaptic plasticity rule that maintains the connectivity required for path integration by integrating visual and self-motion input arriving at different dendritic locations in a neuron. This idea is applied to the central complex of Drosophila, a well-characterized system. The study is timely and well executed, however the generality of the suggested mechanism needs further discussion.

(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 study, which is of interest to students of microbial biogeography, explores the distance-decay relationship for soil prokaryotic communities in alpine and temperate grasslands. Although the experimental scale and conclusions are fairly substantial, there are concerns about the methods, as well as several concerns related to the inferences and presented 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study investigates the relationships of endothelial cells that comprise the coronary vessels of the heart in mouse and humans. Starting from the knowledge that two sources of progenitor cells contribute to the coronary vessels, the work shows that adult coronary endothelial cells do not retain expression memory of their source, nor do they respond differently to cardiac injury. Finally, human datasets were generated and compared to mouse to show overall strong similarity between the species in coronary endothelial cell subtypes, suggesting that mouse is a relevant model for translation to human treatments and therapies.

(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 represents a significant contribution to the study of gene expression and brain evolution in primates, which will be of interest to the evolutionary biology, anthropology, and comparative neuroscience communities. By performing RNA-seq on 18 taxa across the breadth of the extant primate phylogeny, the authors can examine how gene expression levels have changed over the past 70 million years of evolution and attempt to infer genes that contribute to the large amount of variation in brain size across primates. While the data set itself is valuable and exciting, methodological detail is lacking and several opportunities to leverage phylogenetically informed methods to study gene expression and brain size evolution are missed.

(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 work investigates cochlear physiology by applying terahertz wave modulation to the outer hair cells (OHCs). Improved cochlea sensitivity and a change in potassium membrane current is demonstrated. The work is of clear interest to auditory neuroscientists and has the potential for future clinical interest.

(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 is of potential interest to neuroscientists interested in neural coding. It presents a novel family of statistical models that is more accurate than simple models that assume independence between neurons. The results provide evidence that the proposed encoding models accurately capture key statistics of realistic neural activity, and that Bayesian decoding based on them can be accurate and efficient. The manuscript would benefit from a more complete comparison with other 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript finds common molecular features in the blood of three "Mendelian Disorder of the Epigenetic Machinery" (MDEM) mouse models. These shared features (chromatin accessibility and gene expression) may underlie some of the clinical similarities of these disorders. This work will be of interest to researchers, and to some clinicians studying MDEM and epigenetic variation in mammals. Additional analyses are needed to strengthen 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Vertical patterning of the shoot meristem is regulated by a well-characterized feedback loop involving the CLAVATA3 peptide, the CLAVATA1 receptor-like kinase and the WUSCHEL transcription factor. Cell loss from the Peripheral Zone of the meristem, due to production of lateral organs, requires a compensatory size increase of the stem cell domain, i.e. there is a need to understand how stem cell activities in the Central Zone and Organizing Center are coordinated to regulate organ initiation and cell differentiation in the Peripheral Zone. The authors identify a new signaling pathway to control shoot meristem function in Arabidopsis, suggesting that the peptide CLE40 and the receptor kinase-like protein BAM1 act from the Peripheral Zone to stimulate stem cell fate via WUSCHEL expression, and antagonistically to the CLV pathway. The model is novel and exciting and will be of interest to plant scientists as well as those interested in developmental patterning. Some additional evidence is required to fully sufficient to support all claims in 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper studies the role of phase separation in replication initiation, with a focus on Cdt1. Sorting out the relative roles of phase separation and other mechanisms will require a detailed dissection of the amino acids driving phase separation, which can then be used to probe the role of phase separation in cells. Here the authors perform extensive and comprehensive analyses that are well done and that set the scene for a full dissection of the role of condensation in replication initiation inside 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. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript by Nakamura et al provides additional information on the impact of bias in the scientific review process. The authors find that on average applications from White scientists scored better than those from Black scientists. However, blinding reviewers to race worsened the score of the White scientists with no impact on the score for Black scientists. In view of the recognized value of increased diversity in science, the additional information provided in this manuscript adds new data to this discussion. Potential solutions to this bias though are complex.

(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 is of broad interest to those in the field of immunometabolism, a field which has largely used the mouse as an experimental system. The descriptive work is the first of its kind to demonstrate important aspects of biological variability and hidden aspects of mitochondrial function in human immune 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 provides interesting insights in the control of insulin secretion. The authors identify a subset of 'first responder' beta-cells (the cells that secrete insulin) that - possibly -influence the activity of other beta-cells. They characterise some of the properties of these cells and demonstrate the existence of a fascinating possible hierarchy within the islet. With the data consolidated by more rigorous statistical analyses, this paper will make a useful addition to 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript models a particular class of genetic lesions observed in the imprinting disorder and overgrowth syndrome, Beckwith-Wiedemann syndrome (BWS), using a highly tractable mouse model. Because more than one gene is abnormally expressed in BWS that is caused by loss of imprinting of H19 and IGF2, the authors vary the expression of both genes to investigate the source of the cardiovascular phenotypes and are able to ascribe independent heart phenotypes resulting from IGF2 overexpression and H19 loss of expression.

(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.)