Evaluated articles

Evaluation Summary:

There is currently a lack of available fine-grained infant-dedicated cortical parcellation maps. The present study fills an important gap in the research of infant brain development by generating an age-dependent functional brain parcellation from birth to 24 months, leveraging on the 1064 high-resolution longitudinal resting-state fMRI scans from 197 infants. These age-specific parcellation maps have the potential to facilitate scientific discoveries, comparisons, and validations in brain functional development. Moreover, the proposed method of establishing functional correspondences across individuals using functional gradient densities can also be applied to study brain changes across lifespan.

(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 will be of interest to neurophysiologists and system neuroscientists interested in memory and more specifically in hippocampo-cortical interactions. Using a combination of imaging and electrophysiological techniques, the study characterizes neocortical activity patterns around awake hippocampal ripples. Unlike sleep ripples, cortical activity seems to be dominated by inhibition around ripples but differences between intrinsic activity and synaptic transmission highlight complex interactions in the underlying neuronal circuits and dynamics.

(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 Cretaceous dinosaur Spinosaurus has recently drawn significant attention as it was hypothesized to be the first aquatic dinosaur, using tail-powered swimming in surface waters and at depth. In a reappraisal of the "aquatic hypothesis", new lines of evidence – including the CT-based skeletal restoration of Spinosaurus and biomechanical tests – support the alternative "semi-aquatic hypothesis". This article will be of interest to vertebrate paleontologists and functional morphologists, as well as wider academic and non-academic audiences.

(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 presents an interesting and informative study on two regulatory elements found near atrial fibrillation-associated regions and their effect on Tbx5 expression and arrhythmia susceptibility in a mouse model. The multilevel approaches and analyses are rigorous, and the conclusions are justified by the data. Tbx5 expression may be of relevance for human atrial fibrillation and disease risk in patients, and the work is of potential interest to scientists in the fields of gene dosage, gene regulation, genetic susceptibility, genetic variants and cardiovascular biology.

(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 important work provides compelling evidence for the biological plausibility of the Successor Representation (SR) algorithm. The SR is a leading computational hypothesis to explore whether neural representations are consistent with the hypothesis that the neural networks in specific brain area perform predictive computations. Establishing a biologically plausible learning rule for SR representations to form is of high importance in the field of neuroscience. This is also important for comparing the predictive ability of neural circuits with other predictive frameworks designed in machine learning.

(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.)

eLife assessment

This is an important paper that is methodologically solid and highlights structural covariance as the neuroanatomical basis underlying individuality in genetically identical mice. The approach to individuality is very well designed, and the use of brain imaging and anatomical covariance as the underlying mechanism is well thought out. The statistical methods, while overall sound, require further justification and exploration. This paper will be of broad interest to neuroscientists, especially those working in brain plasticity or understanding unique and shared environmental influences on individuality.

Evaluation Summary:

This paper introduces a light microscopy pipeline for imaging and fast reconstruction of the synaptic connections of individual neuronal types in the fruit fly and for correlated investigation of circuit structure, function and behavior in the same animal. Because of its speed and accessibility, this approach enables mapping of selected neuronal circuits of multiple animals across different conditions and behavioral states, thus filling an important gap in brain research.

(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 valuable paper proposes an innovative iterative masking approach that enables models such as the MSA Transformer to generate new protein sequence designs, which are validated using a wide-ranging set of computational experiments. A key strength of the MSA Transformer is the ability to learn and generalize across protein families, enabling impressive performance across a range of downstream tasks. However, to date, these models have not been used to generate new protein sequence designs. The approach proposed in this paper is quite novel, and a number of metrics are used to examine the resulting performance of the MSA Transformer at generating new protein sequences from specific families.

(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:

Almeida and Macklin provide one of the first studies to closely examine early oligodendrocyte behaviors at high resolution. These studies use live imaging in zebrafish to provide valuable new insights about the earliest onset of myelination in the central nervous system and add to a body of work showing how oligodendrocytes initiate and maintain myelin sheaths.

(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:

In this manuscript, of interest to those studying insect reproductive biology and specifically mosquitoes, the authors show that females of the yellow fever mosquito retain eggs when fresh water is not readily available. The authors then use RNA expression analyses to identify genes potentially involved in the trait. This leads the authors to focus on two genes that seem to be recent duplicates. The authors generate genetic knockouts and use these to show that these two alleles affect the trait in question. The study includes interesting and technically impressive experiments, but the framing in the context of previous work could be improved.

(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:

Engineering NLR proteins to improve disease resistance in crop plants is a major goal of the field. This study applies knowledge from structural and evolutionary studies of the rice NLR protein Pik-1 and cognate effector protein AVR-Pik to engineering of new disease resistance genes. The authors nicely demonstrate that it is indeed possible to engineer resistance proteins with broad recognition specificity for the rice blast fungus. The work is of interest to colleagues in synthetic biology, protein engineering and plant-pathogen interactions.

(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.)

eLife assessment

This paper reports on important observations regarding human CD8 T cells that express shared T cell receptors amongst individuals and exhibit poly-specificity directed mainly to several unrelated viral antigens. Although the majority of the claims are convincingly supported by results from both in silico and experimental approaches, mechanistic molecular details underlying poly-specificity remain incomplete. The results from these studies will enhance the ongoing debate on T cell specificity and potentially, will impact fields related to immunology, for example, immunoparasitology, cell biology, and vaccine development.

Evaluation Summary:

The manuscript by Li and coworkers characterizes sorted human non-hematopoietic bone marrow cells by scRNA-seq and predicts their lineage relationships and possible interactions with mature and immature hematopoietic cells. Transcriptionally-different stromal cell subsets are identified, and their lineage relationships, cell-cell interactions and possible specialized functions are inferred or predicted from in-silico studies, paving the way for future functional and validation studies. This resource significantly adds to the current understanding human non-hematopoietic bone marrow stromal cells and their hematopoietic regulatory functions.

(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:

A meta-analysis of over 14,000 fMRI studies revealed a principle rostral-caudal gradient in the lateral prefrontal cortex. This gradient reflected an internal/external axis, which helps to organize the LPFC's involvement in widespread processes from affect, to memory, to control, and action. This is an important contribution to the literature, particularly as a meta-analytic approach has not been applied to this axis of organization and can complement the limitations of single studies. The evidence for the conclusions could be strengthened by ruling out bias in the analysis and drawing a clearer relationship to functional networks.

(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 makes a comprehensive survey of the relationship between mtDNAcn and the personality dimensions, as well as how and whether they mediate the relationships between personality dimensions and mortability as well as other behavioural measures that may lead to mortality. More work needs to be performed to truly understand the relationship between personality dimensions and mortality, as well as the physiological traits (like mtDNAcn) that may be mediating it.

(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:

Liu et al. describes an unsupervised method that clusters colorectal cancer samples based on perturbations to gene interactions. They show that this method strongly suggests 6 distinct clusters of samples and identifies phenotypes associated with the clusters, including survival, drug response, immune phenotype, response to immune checkpoint inhibitors and perturbed pathways. This is an interesting and significant manuscript, which has been well conducted.

(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:

Fan and colleagues disclose the development of covalent TEAD inhibitors and they report on the therapeutic potential of this class of agents in the treatment of TEAD-YAP-driven cancers (e.g., malignant pleural mesothelioma, MPM). Optimized derivatives of a previously reported covalent TEAD inhibitor are described and characterized, using diverse profiling approaches that range from biochemical and cell-based assays to X-ray co-crystallographic analysis and in vivo efficacy in a relevant mouse xenograft model. The manuscript represents an impressive and deep characterization of this small molecule class. The authors' claims and conclusions are very well supported and justified by the data, although differentiation from a very closely related compound termed K-975 is not entirely clear as currently presented.

(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 study provides a thorough functional analysis of three mutations in the BRCA2 gene that do not seem to necessarily cause breast cancer. The authors use functional assays in cancer cells and with recombinant proteins to determine that two BRCA2 variants, S1221P and T1980I, are indeed pathogenic, while the T13461 variant is fully functional and benign. The strength of the study is the rigorous assessment of these mutations in a variety of established assays for BRCA2. The work is likely to have a broad impact in the breast cancer 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 from Singh and colleagues investigates neural connections between the central amygdala and the zona incerta, two subcortical brain regions previously implicated in pain, and further describes the role of the zona incerta to preclinical pain-related behavior in mice. This study employed anatomical tracing, electrophysiology, optogenetics, chemogenetics, and behavioral assays in various pain modalities to link the zona incerta to pain modulation by providing new evidence for a direct inhibitory connection from the central amygdala to the zona incerta that could explain neuropathic pain hypersensitivity. While rigorous, well written, and well executed, the study in its current form lacked evidence to directly support the PKCδ neurons in the central amygdala projecting to the zona incerta as being explicitly involved in this process.

(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 paper by Smith and colleagues provides a framework for understanding a seemingly paradoxical observation in human genetics: two phenotypes may be closely correlated to each other, and the patterns of genetic variation that influence both phenotypes may be widely shared at the genome-wide level, but there are often specific genetic variants that show discordant patterns. Though the observations in this paper are derived from analysis of metabolic phenotypes, this may have broader relevance to interpreting the results from disease-related genetic association studies, and shed light on the processes that connect different disease 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. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)