Evaluated articles

Evaluation Summary:

This paper describes the use of three well-established mathematical models of cervical cancer to estimate the impact of COVID-19 related-delays in screening access on cervical cancer incidence and delays in diagnosis. Consistent with previous work and the known biology of cervical cancers, the findings that short delays have relatively small effects on population-level cervical cancer risk are reassuring overall, but the impact of screening interval and screening test performance suggest that existing disparities related to screening access may be exacerbated. These results should be useful for policy makers in planning responses to future pandemics or other sources of sudden restriction of screening availability.

(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 proposes a computational model that combines biologically detailed elements with more simplified components to provide a comprehensive model of synaptic plasticity. It includes the stochastic character of many of the biophysical processes and introduces a new way to readout the plasticity cascade. It is evaluated against impressively many published experimental studies of hippocampal plasticity. The paper should be of interest not only to computational neuroscience but also to the synaptic neuroscience community but will benefit from a clearer description of assumptions and weaknesses, and a clearer separation of the essential elements in this model from the less critical elements.

(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, of interest to those studying the evolution of immunity, investigates the evolutionary history of a recently described herbivore-associated molecular pattern (HAMP) receptor, INR, which perceives the caterpillar-derived peptide HAMP, In11. The authors compare INR homologs to identify evolutionarily conserved residues and use chimeric fusion proteins to investigate specificity. The findings presented are valuable and supported by convincing experiments and 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.)

Evaluation Summary:

This paper will be very interesting to the large class of neuroscientists who study functional roles of glycoprotein hormone receptors in the central nervous system. It provides detailed tissue-selective gene and receptor distributions of the three anterior pituitary hormones, and thus likely facilitates further relevant studies by other scientists.

(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 manuscript compares COVID-19 mortality during the pre-Omicron and Omicron emergence periods in several countries and finds evidence suggesting the Omicron variant was associated with lower mortality than previous dominant variants. This paper will be of interest to infectious disease scientists both for its content and its methods, as it validates that population-level variant frequency can be a good proxy for individual-level variant data to derive insights on variant biology with population data.

(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:

The findings of the paper are of interest to scientists studying the learning of abstract representations. It provides insights into how feedforward networks evolve during a process of learning to map stimuli onto abstract classes via gradient descent. The results are appealing and the analyses thorough. As well, the paper makes some experimental predictions. It could benefit from a deeper discussion on how the findings may generalize to biologically more realistic networks and tasks.

(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 early differentiation of germ cells, those that will form egg and sperm, is a critical and nearly universal step in animal development. This paper reveals new layers of molecular and cellular regulation that control this process in the fly, and as such be of broad interest to cell and developmental biologists, especially those interested in critical cell fate decisions. The paper contains a wealth of experimental data demonstrating that processes generally thought to be restricted to somatic cells alter the differentiation of germ cells, but provides only limited functional interpretation of the observed phenotypes.

(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 neuroscientists studying mechanisms regulating synapse formation and maintenance. Following up on the previous work by the authors on trans-synaptic signaling complexes involving neurexins and cerebellins, this study shows that the basic framework of the complexes operates broadly across different synapses in the brain albeit with subtle differences. The experiments are carefully executed, while some key conclusions could be better supported by additional data.

(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 investigates scenarios in which the environment changes during the course of a decision, and shows that optimal behavior can be highly complex. It will be of broad interest to researchers in psychology, behavioural economics, and neuroscience interested in decision-making in real-world tasks. It also awaits detailed empirical testing.

(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 murine genetic platform reducing fibroblast expression shows normal background indicators of cardiac structure and contractile function. Yet it shows a reduced functional compromise, on ischemic or hypertrophic challenge. This suggests its value for studies of the effect of fibrosis following normal or pathological change.

(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 develops evolutionary simulations to identify the type of molecular networks that can give rise to size control. We now know a lot about the functional consequences and underlying molecular biology of different cell size control strategies, but comparatively less about which factors select for particular mechanisms. The authors address this point in an evolutionary framework. They show that the evolution of a specific cell size control mechanism is dependent on the cell cycle structure. The paper will interest researchers in development, evolution, and physics of biological systems.

(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 addresses the mechanism of entrapment of DNA in the cohesin SMC complex. Through a series of biochemical studies, the paper convincingly demonstrates that DNA enters cohesin rings through the hinge and SMC3/SCC1 interfaces. How such entrapment is regulated is important for different biological activities including sister chromatid cohesion and the formation of DNA loops. The paper will be of interest to researchers in SMC biology, DNA recombination and 3D genome organization.

(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:

Adult zebra finch song is highly stereotyped, and it is driven by correspondingly stereotyped neural sequences in premotor cortical nucleus HVC. By imaging HVC activity in juvenile birds isolated from social contact with tutors, the authors discover that stereotyped HVC sequences can exist even without exposure to tutor song. Interestingly, after tutoring, existing sequences in the HVC of isolate birds transitioned from being uncoupled to vocal output to highly coupled to newly copied tutor syllables. Together, these data provide a fascinating glimpse into mechanistic foundations of how nature and nurture work together to a learned motor sequence.

(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 manuscript will be of broad interest to readers in the fields of biochemistry, structural, molecular, and evolutionary biology. It outlines a systematic approach in characterizing nuclear receptor ligands based on the conformational ensemble of the receptor, further exploring the idea that perturbation of the ensemble orchestrates function. The results from the combined use of experiments and simulation are promising, suggesting that the change in the ensemble is responsible for 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

The complete metamorphosis of the higher insects is one of the most fascinating and complex processes in nature: The discrepancy in form and function between larvae, pupa, and adult insects is breathtaking, begging the question of how these forms and functions can so seamlessly follow each other. For the highest-order brain centre of the insects, the mushroom body, the authors provide a masterpiece analysis of this process at the cellular level. Given the breadth and depth of the data that the authors present, the current study will serve as a reference for the field of developmental neuroscience for many years to come; this study is eagerly awaited in the field. Perhaps ever more importantly, the insights into the relationship between evolutionary development and individual development at the cellular level might have a profound and lasting conceptual impact on life and natural sciences.

(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.)

eLife assessment

This paper is a fundamental work in developmental biology that supports its findings with compelling evidence drawn from both theoretical and experiment insights. This work will be of interest to researchers in the fields of developmental and stem cell biology as it provides a potentially general mechanism for the control of a proliferative cell population.

Evaluation Summary:

This study builds on previous observations of arginine depletion in the pancreatic tumor microenvironment, with the goal of developing and using a cell culture medium (TIFM) that better recapitulates nutrient levels in the TME. With this system, the authors identify arginine biosynthesis as an adaptation of pancreatic cancer cells to arginine starvation. This work reinforces a timely message that builds upon the push for optimizing and reformulating cell culture media, so as to improve fidelity, and better recapitulation of physiological/pathophysiological cellular behavior. The latter is in turn critical for translational and therapeutic applications. The work will be of interest to tumor 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 #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This paper provides insight into a potentially new genetically defined subset of prostate tumors driven by concurrent loss of two tumor suppressor genes. This study both validates previous findings and provides new data that is compelling overall. With some additional statistical and biochemical evidence to support the conclusions, the work would be of interest to cancer biologists studying molecular mechanisms of prostate 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

The authors identify a novel developmental role for the beta-adrenergic system in the regulation of mammalian cardiac regenerative capacity. Using genetic and pharmacological loss-of-function approaches, the authors identify a link between Yap and β-adrenergic receptor blockade. The conditional genetic loss-of-function studies are a particular strength of the manuscript and provide strong support for the Gas/Yap-dependent nature of the cardiomyocyte proliferative response to beta adrenergic blockade. Given the widespread use of beta blockers in the clinical management of heart failure, the findings are potentially very important. However, further evidence is required to substantiate the induction of bona fide cardiomyocyte proliferation and cardiac regeneration and clarify the associated 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 #1 agreed to share their name with the authors.)

Evaluation Summary:

The research presented in this manuscript is focused on testing the role of peroxiredoxin (Prdx5) and heterogeneous nuclear ribonucleoprotein K (hnRNPK) in bone biology and osteoporosis. Using cell-base and animal models, as well as various experimental methodologies the authors demonstrated that Prdx5 is upregulated during osteogenesis but suppressed during osteoclastogenesis. This novel function Prdx5 was found to be associated with binding and regulation of hnRNPK which controls the expression of genes involved in osteoclastogenesis, such as osteocalcin (Ocn).

(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.)