Evaluated articles

Evaluation Summary:

Chen et al. demonstrate a pro-survival role of the NRF2/DKK1 axis in mesenchymal stem cells. Furthermore, the authors provide evidence that targeting this pathway can enhance survival in response to liver failure in vivo. These data highlight a novel signaling pathway to enhance efficacy of MSCs in promoting regeneration.

(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:

Carboxysomes enable the efficient fixation of carbon dioxide in specific bacteria. Phase separation has been invoked as a mechanism that drives the formation of carboxysomes. The current work focuses on the biophysical principles of how one of two essential specific protein components enable spatial regulation over carboxysomes. This important work highlights the connection between oligomerization via specific molecular interactions and phase separation. The work is of interest to the areas of biochemistry and carbon dioxide fixation as well as phase separation.

(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:

Drosophila ovarian follicle cells have been utilized as a model system to study organogenesis and epithelial tumorigenesis. The analysis of single-cell transcriptomes of follicle cells now shows that transcriptionally distinct cell populations emerge shortly after induction of loss of polarity. Strengths of the work include the use of advanced single cell omics and imaging analyses to identify cell types and factors playing a role the disruption of polarity and the implications of this work for epithelial cancers. The authors' claims are generally well supported by the data and analyses. Weaknesses include the lack of high magnification images and need to clarify motivation for the study and highlight the biology rather than technical advances in the results section. Overall, this work is viewed as an important contribution to cell biologists who work on the epithelial morphogenesis or tumorigenesis.

(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 addresses G protein-coupled receptor signaling and proposes an additional site on Beta-arrestin2 (arrestin 3) as being responsible, in significant part, for the downregulation and likely onward signalling from endosomes of a range of GPCRs. The cell biology appears to be thoroughly carried out and data presented in a statistically appropriate manner. With some textual changes and minor experimental clarification of the route taken and molecules involved, this work will be of broad 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 #3 agreed to share their name with the authors.)

eLife assessment

This paper provides evidence that an unhealthy lifestyle during adolescence accelerates epigenetic age in adulthood, and that these associations are largely explained by the effect of shared genetic influences. The main strengths of this valuable paper are the relatively large sample size, longitudinal assessment of lifestyle factors, and sophisticated statistical analyses. The paper is methodologically compelling and will be of interest for a broad audience, including individuals working on methylation, epidemiology, and/or ageing.

Evaluation Summary:

The authors use high spatial resolution MEG in humans to link two important components (time - transient bursts, space - waves) of neural sensorimotor dynamics by investigating how transient beta bursts propagate in the brain. The authors find two directions of propagating waves during beta bursts. The work links two fundamental aspects of neural dynamics which may yield new insights into the origins of sensorimotor behavior, with wide appeal to neuroscientists and clinicians. The reviewers considered the methodological work largely sound, although concerns were raised by the reviewers to what extent the travelling waves correspond to underlying neural activity or reflect the generative nature of field potentials.

(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 will be of interest to researchers studying meniscus homeostasis and knee osteoarthritis. It uncovers distinct subtypes of cell populations in inner and outer part of human meniscus using single-cell RNA sequencing. In particular, this work further identifies how alterations in meniscal cell populations may contribute to inflammation and osteoarthritis and thus serves as a resource paper for 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript reports the development of a proteo-genomic screening methodology to identify protein-protein interactions between secreted proteins and their cell surface receptors. The authors use a CRISPRa-based approach to overexpress membrane proteins in cells and then use magnetic cell sorting to identify receptors that bind candidate ligands. This approach leads to the identification of several novel interaction pairs that are validated biochemically, including receptor tyrosine phosphatase ligands and other interactions with implications for immune system function. The work is of interest to a wide variety of fields including biochemistry and signaling.

(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 provide a summary of single and double mutants in five self-cleaving ribozymes using next-generation sequencing. They dissect their data in terms of epistasis effects, which provides a new angle to understanding ribozyme function. In principle, this allows conclusions to be drawn on bases involved in pairs and in catalysis that have the potential to be of use to the field, although there is also a series of technical weaknesses that should 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Identification of transcriptional phenotypes driven by TBI across meningeal immune cell subsets and the effect of aging on these responses is an important and not well-defined area in the field. Multiple complementary and high-end approaches are taken to demonstrate the long-lasting effects that TBI drives in the brain and support the main findings of the manuscript. This manuscript will be of interest to readers in the field(s) of neuroimmunology, aging, and traumatic brain injury.

(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:

Menjivar et al. identify a previously unrecognized role of myeloid cell Arginase1 (Arg1) activity in shaping the anti-tumor immune response in pancreatic ductal adenocarcinoma (PDAC). The proposed therapeutic combination is a new approach for pancreatic cancer, with an enhanced response to immune therapy upon arginase inhibition.

(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 authors investigate what type and degree of information (either absolute, relative, or a weighted combination of both) is used by bumblebees when retrieving the value of an item. There is recent evidence in humans and birds that suggests that these organisms use a combination of absolute memories and remembering of subjective ranking in these tasks. The authors conclude that bumblebees indeed use remembered ranking, but that they seem not to be able to retain (or at least utilise) absolute property information for very long. The absence of relevant work in invertebrates would make this study a potentially valuable addition to the scientific literature.

(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:

Li et al. use biochemical binding analysis to explore the role of Rabphilin 3A in dense-core vesicle exocytosis in neuroendocrine PC12 cells and in an in vitro SNARE assembly assay. They propose that the Rph3A binding to SNAP25 pre-structures the protein to efficiently assemble with Syntaxin and VAMP2, and thus, promoting the vesicle docking and priming process. This work will be of interest to scientists studying the molecular basis of synaptic vesicle release.

(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 will be of interest to readers in the field of microbiology, particularly those interested in bacterial interactions, secretion systems, and stress responses. It identifies the molecules and mechanisms that explain a competitive interaction between two soil-dwelling bacterial species. The data support most of the conclusions of the manuscript, but some controls are lacking and some of the interpretations are not fully justified by the experiments shown.

(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 reports the CryoEM structure of OmcZ cytochrome nanowires of Geobacter sulfurreducens, the third cytochrome nanowire of Geobacter to be structurally resolved. OmcZ differs structurally from these previously determined nanowire structures, showing a different heme chain configuration. Based on these and other differences the authors speculate about the evolutionary origin of these nanowires and the mechanism of long-range electron transport. This manuscript is an important contribution to the field of electron transfer and will be of interest to everyone working in electron transfer and filament formation and interested in their evolution.

(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 article seeks to address a key question in protein biophysics: are the amino acid positions (and mutations) that influence allostery conserved across homologs of a protein family? Or is allostery implemented by a distinct set of residues that varies amongst homologs? To address this question, the authors follow an innovative approach that combines deep mutational scanning with machine learning. Significant revisions are required to clarify whether the conclusions of the study are well-supported by the data. The work is potentially highly relevant to protein engineers and biophysicists.

(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 is of interest to organismal biologists and evolutionary scientists who study cognitive and behavioral sex differences including those with interests in the evolution of complex spatial behaviors. Using intensive field monitoring and experimentally induced navigational challenges, the authors examine two different hypotheses for sex differences in spatial ability in three species of poison frog. A rich and complex story emerges, including from the provision of evidence that is consistent with (but not necessarily yet definitively or exclusively in support of) the hypothesis that androgens may inadvertently affect spatial ability.

(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 examines the importance of PKA-dependent mTORC1 activation for the weight-loss effects of liraglutide. The work has the potential to provide important insights, but at present is deemed preliminary as it lacks details on the mouse model and control data and needs a more in-depth analysis of the metabolic phenotype.

(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:

Iron acquisition is an essential problem for microbial growth and survival. Host defense mechanisms generally reduce iron availability and microbes often find themselves in iron poor environments. This study provides new insights into how the fungal pathogen Candida albicans obtains iron during infection.

(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 biologists and climate modelers that study the impact of environmental stress (especially multiple stressors) on marine life. The authors show that exposure to low pH (ocean acidification) decreases the ability of two mussel species to survive freezing stress. The authors measure multiple biochemical parameters to try and identify the mechanisms underlying the change in freeze tolerance, but future work will be needed to resolve the underlying mechanism in detail.

(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.)