Evaluated articles

Evaluation Summary:

This is a paper that will be of particular interest to neuroscientists with a focus on food intake and neural responses to food ingestion. This paper provides new insights into how the body responds to weight loss and helps identify those that may not be successful.

(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 authors use theoretical models to examine the joint evolution of different cheating strategies: selfish cheating (not contributing to a common good), and manipulative cheating (inducing a competitor to preferentially provide benefits to the cheat). The models seem well formulated and the results robust. That said, improvements could be made to the presentation to clarify the assumptions and wider applicability of the model. An improved article would provide a better understanding of the mechanisms behind cheating, which would be of interest to readers working on the evolution of cooperation, potentially opening up new directions for theoretical and empirical work.

(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 has potential value for researchers in several areas of cognitive and systems neuroscience. Range adaptation is a widespread property in neuronal circuits, and a network mechanism that relates neuronal adaptation to behavioral outputs is a valuable addition to the literature. However, limitations in the current framing and analyses leave some uncertainty about the interpretation of the results and their broader applicability.

(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 tackles the timely and interesting research question of whether meningeal lymphatic drainage is required for the control of brain infection with Toxoplasma gondii. It contains a sophisticated experimental approach using cutting-edge methods, it has an easy-to-follow narrative, and comes up with an interesting albeit negative finding which the authors even tried to explain by an additional set of experiments. Although there are some limitations and weaknesses of the paper in its present form it will certainly contribute to the growing body of literature on how the once "immune-privileged" CNS is protected against environmental challenges.

(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 manuscript shows that mutations in the gene encoding an enhancer chromatin-modifying enzyme MLL3 cooperate with Myc overexpression to drive hepatocellular carcinoma in mouse models. The authors identify Cyclin Dependent Kinase Inhibitor 2A (Cdkn2a) as a critical direct target gene of MLL3. Overall, the manuscript makes a compelling case that MLL3 is a hepatocellular carcinoma tumor suppressor that directly binds and activates the Cdkn2a locus. This study provides important insights for cancer biologists and those interested in specific epigenetic mechanisms that regulate liver cancer development. Editorial and some experimental suggestions were made to strengthen the work.

(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:

By performing homeostatic longitudinal IgH repertoire analysis of human memory B cells and plasma cells, authors draw two major unique conclusions; first, a high degree of clonal persistence in individual memory B cell subsets with inter individual convergence in memory B and plasma cells; second, reactivation of persisting memory B cells with new rounds of affinity maturation during proliferation and differentiation into plasma cells. These conclusions provide a significant insight into how human memory B and plasma cells are generated in a homeostatic 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Keine et al study the role of the RhoGTPase Rac1 in neurotransmitter release by ablating this protein at an age when synapses are in an almost mature stage. They describe an increase in synaptic strength, which they interpret as an increase in release probability or fusogenicity of synaptic vesicles. They also describe subtle effects in the timing of release, which point towards a mild defect in positional priming. The study delivers important information on the role of Rac1.

(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 develops a resource allocation model for E. coli growing under steady-state conditions. The model describes both growth rate and yield and has been subjected to validation by comparison with a compiled data set. The manuscript addresses an important problem of interest to a wide range of investigators. At the same time, the authors would need to explore different assumptions for the housekeeping proteome fraction (phi_q) to ensure the model is robust.

(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 current study examined in detail the role of oxytocin neurons in the hypothalamus in regulating food intake. The current study extends our understanding of the role of this peptide in regulating complex behaviors.

(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:

Hu and colleagues describe the discovery and characterization of a new class of reversible palmitoylation (PLM) binding site TEAD inhibitors. X-ray co-crystallographic analysis reveals that the ligand class, identified from a screen of 30,000 small molecules, binds to a new site within the auto-PLM site. The TM2 lead compound inhibits the growth of NF2-deficient cell lines. The discovery has the potential to significantly impact the design and development of new effective TEAD inhibitors. Some clarification or additional data are required to support and justify some of the authors' claims regarding the molecular significance of this new class of inhibitors.

(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:

Recent studies of the brainstem locus coeruleus (LC) noradrenaline system have demonstrated a partially modular organization in which specific classes of neurons can serve distinct functions or exhibit module-specific co-activity. However, how noradrenaline cell classes function in a modular way is not clear. The authors have accomplished a technical feat by recording up to eight LC neurons at once using ex-vivo, multi-patch recordings. In doing so, two empirically-derived classes of LC neurons were identified and the analysis of electrical coupling between these neurons established some principles of local circuit communication occurring preferentially within the defined cell classes.

(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 individuals working on genome stability and B lymphocyte development. Using knockouts for the genes encoding the structure-selective endonucleases GEN1 and MUS81 in mice, the authors show that the absence of both proteins is incompatible with embryonic development, with selective loss in mature B-cells inhibiting germinal center formation. This is the first study of these enzymes in an organismic context and in primary cells, revealing insight into the in vivo consequences of loss of MUS81 and GEN1 functions not previously accessible through studies in cultured 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 #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper explores the use of 2D high-resolution template-matching (2DTM) to locate and discriminate highly similar macromolecules within cryo-EM images of focused ion beam-milled cells. It demonstrates that differences in the 2DTM signal-to-noise ratios for located targets against multiple search templates can effectively segregate a mixed population of similar structures, as well as present a formal analysis strategy for probabilistic assignment of species within the mixed population. Because the identification of distinct structural states of macromolecular complexes inside the cell is a fundamental problem in 3D visual proteomics, this paper will be of broad interest to both structural and cell 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 notion of transcription factors as composed of interchangeable parts where DNA binding activity can be separated from activation activity has been a dominant paradigm in molecular biology for decades. However, recent evidence suggests that activation domains may contribute to binding specificity as well. This paper describes the use of single-molecule imaging of endogenously tagged transcription factors to dissect how transcription factors move in the nucleus and how these dynamics are related to functional protein domains. These results will be of interest to the transcription and gene regulation fields, but the conclusions require additional experimental support.

(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 describe their work on an atlas of associations between polygenic scores for 129 different traits representing a variety of quantitative phenotypes and diseases, and a large set of metabolites measured in up to 83,000 participants in the UK Biobank. These associations are all available via a public browser, and may be used to identify candidate intermediate phenotypes, as well as potential biomarkers of disease.

(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.)

Evaluation Summary:

This study investigates the potential role of kin selection in driving social behaviours among siblings in wild mountain gorillas. Using an impressive dataset of 14 years for 157 individuals the authors find some evidence for kin recognition in guiding biases for affiliative and aggressive behaviours. However, the results of the current study will be more convincing if a number of major concerns with the analysis can 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:

This paper will be of broad interest to clinicians and scientists in the area, providing clinical trial data on how the efficacy of monoclonal antibodies targeting SARS-CoV-2 varies according to the variant of concern. The clinical outcome data were consistent with previously reported in vitro data, which are being used to inform the clinical use of monoclonal antibodies. However, as the trial was stopped early, conclusions regarding the efficacy and safety of the individual monoclonal antibodies are limited.

(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 origin of virulence in pathogenic microbes is not understood for many microbial species. The concept of 'accidental virulence' was proposed as a mechanism by which a microbe could acquire the capacity for virulence through interaction with other microbial species, such as amoeba. This paper adds an important new dimension to that concept by showing that the capacity for virulence can emerge from abiotic interactions, such as adherence to plastic.

(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 work by Volante et al. studied a new plasmid partition system, in which the authors discovered that four or more contiguous ParS sequence repeats are required to assemble a stable partitioning ParAB complex and to activate the ParA ATPase. The work reveals a new plasmid partitioning mechanism in which the mechanic property of DNA and its interaction with the partition complex may drive the directional movement of the plasmid.

(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 interesting study the authors combined innovative object-based conflict assays with optogenetic silencing to probe the role of the perirhinal cortex in motivational conflict. The manuscript is well-written and the approach was adequate. The findings provide new insight into how conflicting motivation is processed and would benefit from additional analysis and experimental investigation to more conclusively support the interpretations.

(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.)