Evaluated articles

Evaluation Summary:

The manuscript presents data that high expression of Protein Phosphatase 1 (PP1) inhibitor in triple-negative breast cancer contributes to poor outcomes by downregulation of an important kinase, GSK3β. The study clearly demonstrates that changes in PPP1R14C expression alter the behaviour of the studied cancer cells and mouse models and proposes a mechanism linking PP1 inhibitor to GSK3β. If this mechanism were substantiated, this would enhance our understanding of the pathophysiology of this important disease and might suggest new treatment options.

(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:

Caner/cancer metastasis-induced bone loss-mediated fracture is a serious clinical problem. In this regard the authors have done an interesting study to show how miR155 exhibits a catabolic effect on osteogenesis and bone mass phenotype via interaction with the Sphingosine 1-phosphate receptor-1 (S1PR1) gene. The study suggests that inhibition of miR155 could be a potential strategy for bone regeneration and bone defect healing.

(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 presents DATES, a method to infer the timing of admixture events using genetic data from present-day or ancient individuals. This is a robust method that is useful in the field of paleogenomics and outperforms existing methods. In this manuscript, DATES is applied to >1000 ancient human genomes to characterize major admixture events during the European Holocene. This work will be of interest to scholars in the fields of population genetics, paleogenomics, archeology, biological anthropology, and history.

(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 explores the utility of cell free DNA analysis in non-malignant disease using epigenomic methods. By using brain specific methylation loci the authors identify higher levels of brain-related DNA in the plasma of patients with acute psychotic illness compared with non-disease controls. This paper will be of interest to readers in the field of liquid biopsy.

(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:

Lu et al. provide a new method that looks at whether disorders tend to share excess de novo mutations in genes across the genome. The authors apply the method to nine disorders including a developmental disorder, autism spectrum disorder, congenital heart disease, schizophrenia, and intellectual disability, finding statistically significant overlap between 12 pairs of disorders in de novo mutations that cause a loss of gene function. This method will be of interest to researchers working on disorders caused by de novo mutations, but further clarification of its strengths and weaknesses compared to alternative approaches (mTADA in particular) would strengthen the paper.

(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:

Transcriptional memory is a phenomenon via which certain genes are activated more robustly in response to repeated stimulation and in this manner, are able to "remember" previous experiences. This report dissects the molecular mechanism of inositol-driven transcriptional memory and highlights the key role of the histone mark H3K4 di-methylation, which is deposited independently from RNA Polymerase II activity. This memory-specific H3K4 di-methylation is found to be inherited over multiple cell divisions and to require specific transcription factors and chromatin machinery components to be established and maintained. The work will be of interest to those studying transcriptional regulation and epigenetics.

(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 important and exciting paper demonstrates that the blind cavefish, known for its lack of eyes and increased number of lateral line hair cells, also exhibit physiological adaptations to increase lateral line sensitivity. The authors demonstrate that these adaptations have convergently evolved in multiple populations that have independently colonized cave environments. By leveraging the numerous strengths of the cavefish model, the authors are able to show precisely how neural circuits can be affected by adaptation to the environment.

(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:

The process of secretory vesicle formation, transport, and fusion in yeast has mainly been characterized through biochemical and genetic means. Only limited information was available about the detailed timeline and order of events. This study fills the gap with a high-resolution temporal analysis, which provides new insights into when key components arrive and depart and how they promote vesicle tethering and fusion. The work is experimentally strong, and improvements to the presentation will ensure that the findings are communicated effectively.

(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 describes a microfluidic approach to determine the viscoelastic properties of living cells from their deformation in a fluid flow. Its implementation seems accessible and the method offers the possibility to perform measurements on a large number of cells. This technique could eventually be used in many laboratories, including those not specialized in cell mechanics.

(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:

The premise behind this manuscripts is that concepts from thermodynamics and statistical mechanics can be used to understand brain states and the transitions between such states, just like it is done with transitions between solid and liquid states in well define thermodynamic systems. While this is an interesting attempt to use thermodynamic concepts and equations to analyze fMRI signals, the legwork needed to meaningfully translate those concepts to understand their actual physiological meaning and their relationship to brain function has not yet been achieved.

(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 paper describes a re-analysis of a public fMRI data set which includes measures of resting state connectivity and separate task-based scans of memory encoding and memory retrieval tasks. The paper proposes an analysis method termed "information transfer" that reveals functional interactions between various brain networks during encoding and retrieval as well as differences in these interactions during encoding vs. retrieval. While the methods are potentially interesting, the payoff-or new insight afforded by these methods compared to existing methods-is not fully established.

(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 a comprehensive co-mutation analysis of over 30 thousand cancer patients and 1700+ cancer cell lines to identify associations with prognosis and drug resistance that could have translational value for clinical practice. Once validated, it would provide a useful framework for precision oncology.

“(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 provides an insightful analysis of how animals can use different types of sniffing to quickly find the sources of odorants in natural, often turbulent, environments. As it turns out, the air near the ground is less turbulent but does not provide high precision information about the location of sources that are far away. To get that kind of information, animals have to pause and sniff in the air. Authors show that the relative balance between sniffing near the ground and in the air shifts as the animals approach the source and that this shift matches optimal strategies that can be pursued based on partially observable statistical models of the environment. The paper also includes a very useful set of simulations of odorant flow in the presence of obstacles that will be made publicly available.

(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 manuscript studies the heterogeneity of megakaryocytes using single cell RNA-seq and identifies a subpopulation of CXCR4-high megakaryocytes with immune modulatory roles. The authors also perform functional studies which show that this subpopulation of megakaryocytes promotes bacterial phagocytosis by macrophages and neutrophils. This work would be of significant interest to researchers in the fields of immunology and host defense as well as researchers studying hematopoiesis and megakaryocyte biology because it provides new perspectives on megakaryocyte heterogeneity as well as the role of megakaryocytes in host defense and immune 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 #1 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript by Ferguson and Huguenard examined the mechanism underlying attentional deficits in the haploinsufficient Scn8a mouse model of absence epilepsy. Using a detection behavior paradigm where detection of the cue was dependent on the attention level, they show that Scn8a+/- mice perform worse than controls when cues are of intermediate duration. In the medial prefrontal cortex (mPFC), high gamma-band power, which is presumed to be mediated by activity in parvalbumin-positive (PV+) interneurons, was reduced in Scn8a+/- mice, but optogenetic stimulation of these neurons at low gamma-frequency normalized performance on the cue-based attention task. The results of this study identify mPFC PV dysfunction, rather than seizure activity, as a potentially important cellular substrate, for attention during cue-presentation.

(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 ms examines changes in brain region size in several groups of weakly electric fishes, the Mormyroidea, and the Gymnotiformes and weakly electric catfishes (Synodontis spp.), which evolved electroreception independently of mormyrids. These are an interesting group for examination of mosaic growth. Many analyses are thoughtful and well executed, but there is some concern about whether the observed volumetric decreases are a consequence of the method.

(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 a cross-sectional assessment of the association between COVID-19 related stress and mental wellbeing and whether certain behaviors mediate this association. This work would be of interest to researchers, psychologists, and clinicians involved in the psychological impact of COVID-19. The strength of this work is two folds. First, this is an important and timely topic. The collection of primary data at four time points during the pandemic was innovative. Second, examining the mediatory effects of certain behaviors could shed light on ways to reduce pandemic-related stresses. Future work should address a few limitations, including the inherent biases of using social media as a recruitment strategy and the lack of generalizability.

(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 manuscript will be of strong interest to scientists studying the development of early jawed vertebrates, in particular the extent and structure of their dermal skeleton, but it will also interest a broader audience, given how it connects modern-day morphological techniques to paleobiology. The authors provide the most complete account to date of the body scales of an antiarch stem-group gnathostome; this is the first work to model in 3-D the entire scale cover of such a fossil fish. The authors show that the body scales are varied in form, regionalized and that they comprise two main tissue layers. Based on this they argue that these conditions are plesiomorphic for antiarchs and the gnathostome crown group.

(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 hypoxia inducible factor (Hif) pathway was defined based on its role in cellular adaptation to hypoxia. In this paper, the authors examine the function of the pathway under 'physiological' normoxia in highly aerobic locust flight muscle. They find that a muscle-specific variant, Hif-1alpha2, is induced extensively by flying. By integrating bioinformatic analyses, measurements of gene expression and regulation, metabolites as well as redox regulation and flight assays, it is shown that Hif-1alpha2 plays an important role in sustaining prolonged flight by promoting glucose oxidation and upregulating a reactive oxygen species quencher (DJ-1). This study demonstrates the physiological requirement for two Hif-1a variants in a highly aerobic tissue in migratory locusts, a species that is both physiologically fascinating and a major agricultural pest. The work will be of interest to colleagues studying the physiology of muscles and flight.

(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 study describing the role of Samd14-capping protein (CP) complex in stress erythroid signaling. Using orthogonal cellular, biochemical and genetic complementation approaches, the authors provide evidence to establish a previously unrecognized mechanism for Samd14-CP interaction in regulating Kit signaling in erythroid regeneration in response to acute anemia. Findings of this work will be of broad interest to the study of erythropoiesis and cellular 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. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)