Evaluated articles

Evaluation Summary:

Giant dsDNA viruses, with genomes in excess of 1Mb that encode more than a thousand genes, were only recently discovered and their study offers new opportunities to understand life's evolved mechanisms. In this manuscript, Villalta and colleagues report results on one of the most complex known viruses, the Mimivirus. Its genome is compacted into magnificent fibers comprising apparently repurposed GMC-type oxidoreductase paralogs assembled as a helical coat around genomic dsDNA. Cryo-EM and cryo-ET image analysis yielded a structural model of the fiber in multiple states. The authors also provide some evidence that additional viral enzymes, including RNA polymerases, exist within the fiber assemblies. Pending the resolution of certain issues that emerged in peer review, the study will be of broad interest to 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

The paper would be of interest to neuroscientists and clinician scientists interested in better understanding the mechanism of deep brain stimulation (DBS) in the treatment of Parkinson's disease. Using a combination of electrical artifact-free calcium imaging and electrical stimulation, it probes the effects of stimulation on the neural dynamics of basal ganglia structures that correlate with motor improvement. The key claims are well supported with a convincing discussion of the caveats of the methods used.

(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:

McGregor et al. establish a new reinforcement learning paradigm for songbirds, where instead of auditory feedback (white noise) they use mild cutaneous electrical stimulation as a reinforcer. Their data shows that this somatosensory stimulus can aversively drive pitch changes of a targeted syllable in similar manners as an auditory stimulus does. They further show that the anterior forebrain pathway (AFP) and dopaminergic projections to the AFP are necessary for this non-auditory vocal learning by electrolytically lesioning the output nucleus of the AFP and by depleting dopaminergic input to Area X. Their analysis is rigorous and their data convincingly show shared mechanisms for vocal reinforcement learning using white noise (auditory) or cutaneous electrical stimulation (non-auditory).

(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:

Aida et al use a combination of novel experimental measurements and data processing to wrangle the complexity of bacterial growth for different media conditions. This study represents a clear example tackling the complexity of biological systems from the condition sides (~13,000 growth curves were measured) influencing the growth of a well-defined single specie of bacterium and with a reasonable first pass at data processing. The findings are ultimately simple (with essentially 3 conditions accounting all variability in the system) and easily interpretable.

(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 provides novel evidence that a dopamine D2 receptor antagonist enhances model-based control of behavior, whereas blocking opioid receptors has no effect on the trade-off between habitual responding and goal-directed planning. These conclusions are based on compelling behavioral and computational modeling data and will be of interest to cognitive neuroscientists and computational psychiatrists.

(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 paper, the authors find a link between the emergence of functional connectivity (FC) and changes in regional Cerebral Blood Flow (rCBF) in human infancy from birth to 24 months of age, which will be of interest to the increasing field investigating how the establishment of the brain's functional organization is linked to neurodevelopmental and psychiatric conditions. The data quality and complementarity are impressive for infants over this developmental period (0-2 years). Most of the key claims of the manuscript are well supported by the data. However, the relatively sparse sample and cross-sectional nature does limit interpretation.

(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 will be of interest to developmental biologists and pediatric cardiologists. Addressing the role of NR2F transcription factors in the fish heart, it provides novel insight into atrial chamber patterning and the formation of pacemaker cells. High-quality data are presented supporting the novel finding of a requirement of nr2f1a for restricting the production of pacemaker cells. Yet, data are currently not conclusive in claiming transdifferentiation of atrial cells in the mutants.

(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:

This is an interesting report using computational tools and large amounts of prospective samples from clinical trials to identify different signatures. Using data collected early in the infection in outpatients, the authors aim to identify a set of plasma proteins that can predict a number of outcomes, including disease progression, control of viral shedding, and the onset of antibodies during COVID-19. This study adds to the understanding of the host immune response against COVID-19, as well as the potential of computational tools for the molecular taxonomy of immune responses.

(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 applies super-resolution imaging to the distribution of Ca2+ release channels before and after adrenergic stimulation. They make comparisons between healthy and failing cardiomyocytes. The results are specifically applicable to the understanding of contractile function in cardiac failure.

(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:

Bistable visual perception offers a unique window to study how perception arises and changes via an interaction between bottom-up and top-down processes. In three Magnetoencephalography (MEG) experiments with advanced neural state space analysis, this study demonstrates that two key aspects of bistable visual perception - perceptual content and perceptual stability - are mediated by slow cortical potential (SCP) and alpha-beta-band neural oscillations, respectively. The findings would be interesting for many fields, such as perception, consciousness, and 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This is a well-designed study that will be of interest to cognitive neuroscientists studying event perception and memory, particularly those interested in naturalistic paradigms. The main contribution is in growing our understanding of how interpretational differences of events are reflected in differences in neural representations of those events. While the presented results are convincing, it remains somewhat unclear what processes drive the observed effects, and thus what the role of the implicated brain regions is in memory updating.

(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 presents a combination of in vivo recording and optogenetic experiments that together with modeling brings a significant message: inhibition is functionally present in the newborn frontal cortex having major effects in EEG dynamics. The work challenges the view on the switch in GABAergic excitation to inhibition and extends phenomenological observations to human infant EEG 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:

This paper combines evolution experiments with genomic analysis of environmental samples to study the evolution of colistin resistance in E. coli. It highlights the importance of pre-existing genomic variations in clinical strains in driving the evolution of antibiotic resistance. The results presented here are relevant for clinical and non-clinical microbiologists studying antibiotic resistance to last-resort drugs like colistin. The design of the research is simple and elegant, and the genomic data analysis connects the in vitro findings to the real world. However, the authors could better align the experimental and clinical data, and better clarify their experimental design choices.

(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:

Vaccines are a major influenza control strategy in swine, but perform sub-optimally and are under-utilized. The manuscript describes a detailed genetic characterization of influenza virus variants in vaccinated versus unvaccinated pigs. The results indicate that viral reassortment, which is an important process yielding new strange of importance to man and animals, may be less common in pigs that have been vaccinated against influenza.

(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 is a systematic review by meta-analysis about the effect of calcium supplementation on bone health in people under 35 years old. The authors found that calcium supplementation can significantly improve BMD and BMC in young people. Moreover, a better effect of calcium supplementation was shown in people who are at the plateau of their PBM. A unique feature of this study is that it focused on people at the age before achieving PBM or age at the plateau of PBM, which is different from previous studies that mainly focused on the elderly or children.

(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 describes a new dotplot-based approach for analyzing Low Complexity Regions (LCRs) in proteins. The work is validated against a single protein, compared to existing methods, and applied to the proteomes of several model systems. The work aims to show links between specific LCRs and biological function and subcellular location, and study conservation in LCRs amongst higher species.

(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:

Jia et al. present an exciting machine learning framework named "Selfee" for unsupervised and objective analysis of animal behavior that should draw broad interest from researchers studying quantitative animal behavior. However, there are some unresolved issues for establishing credibility of the method that needs 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. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript reports results of a combined experimental and numerical investigation of magnetotactic bacteria in strong spatial confinement and under the influence of an external magnetic field. Single cells are trapped in micrometer-sized microfluidic chambers. A variety of trajectories are found, which depend on the chamber size and the strength of the magnetic field. A detailed understanding of swimming in simple controlled confinement is essential to predict the behavior of motile microorganisms in the complex environments of their natural habitat.

(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 work offers a simple explanation to a fundamental question in cell biology: what dictates the volume of a cell and of its nucleus, focusing on yeast cells. The central message is that all this can be explained by an osmotic equilibrium, using the classical Van't Hoff's Law. The novelty resides in an effort to provide actual numbers experimentally.

(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 by Kosillo and colleagues presents a series of carefully carried out experiments evaluating the impact of perturbing the mTORC1 and mTORC2 protein complexes selectively in mouse dopamine neurons. By utilizing dopamine neuron-specific Raptor and Rictor cKO mice, this paper elucidated which of these mTOR complexes are responsible for the regulation of dopamine neuronal functions, revealing the importance of mTORC1/2 signaling for the structure and function of dopamine neurons. This paper provided comprehensive data including structural, physiological, and biochemical alterations by genetic deletion of Raptor/Rictor in dopamine neurons.

(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.)