Evaluated articles

Evaluation Summary:

The basis for working memory is controversial in terms of any basis related to neuronal or synaptic activity in sensory cortex during maintenance and the involvement of non-sensory areas especially the frontal cortex and hippocampus. This work uses rare human intracranial recordings to examine another aspect, connectivity between areas, and demonstrates connectivity from sensory cortex to hippocampus during encoding in one frequency band and connectivity in a reverse sense during maintenance. The work has the potential to inform models of working memory.

(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:

Kubiniok et al. use published data sets to bioinformatically study the contribution of tissue type and HLA classical class I gene allotype on the immunopeptidome, the repertoire of peptides presented by MHC class I molecules on the cell surface. This is an understudied and critically important question for understanding CD8+T cell tolerance and immunosurveillance of cancer and other diseased cells and autoimmunity, since it enables accurate prediction of peptide targets for vaccines designed to induce or suppress CD8+ T cell responses. Overall, this is a study that draws attention to some of the properties of the antigen processing and presentation pathway that had not been investigated before, namely the known differential gene expression profiles between tissues resulting in the presentation of tissue-specific antigens on HLA-I molecules, which is very valuable. Additionally this study provides avenues for investigation of the involvement of new enzymatic pathways involved in the generation of HLA-I restricted peptides that are presented to CD8+ T cells for immunosurveillance.

Evaluation Summary:

This manuscript provides the first 3D structure of a novel type of RNA processing enzyme recently identified in bacteria. It convincingly uses cryoEM and biochemistry to describe how this small enzyme makes a new type of homo polymeric complex as required for its activity. The manuscript provides important conceptual novelties that will be of interest for a broad readership of biologists interested in gene expression processes.

(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 paper is of interest to immunologists studying the transcriptional control of innate immune responses. The paper presents a new role for transcriptional regulators in the control of inflammatory properties of cross-presenting dendritic cells that are involved in anti-tumoral and anti-viral immunity. The data support the conclusions but some modifications of the text and additional experiments are required.

(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 tackles perhaps THE central question in metagenomics: what are all these unknown genes and genomes doing!? The authors use recent advances in high-throughput sequencing clustering and homology detection algorithms to systematically integrate unannotated genes into discovery workflows. The paper's exploration results in a wide array of highly informative summative statistics, together with a simple example of how powerful the provided resource can be in generating hypotheses about the function of unknown genes.

(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.)

Evaluation Summary:

This paper will be of interest to experimental virologists and others following the development of "gene drive" technology to promote the rapid spread of specific mutations through a population. The authors first nicely confirm their prior finding that a gene drive virus can be used to transfer mutations into a normal virus when both are infecting the same cell. They then evaluate a strategy with potential to ameliorate the undesirable but expected emergence of viruses that acquire resistance to the gene transfer. Although the experiments are well done, the data are mostly convincing and accurately interpreted, and the presentation is clear, the studies provide a relatively minor advance in fundamental understanding of this potentially innovative therapy.

(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:

Brochet et al. address an outstanding ecological question related to how closely related microbial symbionts co-exist in the gut as stable communities. To tackle this question, the authors use an elegant model relying on honeybees colonized with a defined bacterial community. They provide compelling empirical evidence that a nutritionally complex diet together with microbial metabolic diversity play a key role in enabling co-existence of closely-related honeybee gut microbiota.

(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 will be of broad interest to the vesicle trafficking field, as it defines how an evolutionarily conserved SNX-BAR protein (Mvp1) sorts cargo proteins into membrane tubules emanating from the endosome and recruits a dynamin-like "pinchase" to release the tubule so cargo can move to the Golgi complex.

(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 names with the authors.)

Evaluation Summary:

This paper will be of interest to scientists working on computational modelling of neuroimaging data, and on the neural effects of psychedelic drugs and other pharmacological interventions. The study is well-motivated. The statistical and data analytic methodologies are rigorous and advanced. The with conclusions are well-supported by the presented data. The modelling methodology includes technical innovations that are potentially of broad utility and importance.

(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.)

Evaluation Summary:

The fundamental premise of genome wide association studies for severe malaria is to take a population with confirmed severe malaria and compare with a control group who do not have severe malaria. This paper presents a novel and valuable method for improving power for severe malaria genetic association studies. The method would also be useful for studies of other disease where there is a clinical definition that sometimes includes people who do not truly have the 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 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript addresses the long-standing problem of engineering an in vitro stimulation method for individual inner ear sensory hair bundles that adequately provides a uniform and rapid stimulus characteristic of native inner ear stimulation. The authors address this unmet need with development and characterization of a light-based stimulus to generate rapid photonic force capable of deflecting a range of hair bundle geometries, including amphibian and mammalian vestibular and auditory hair bundles. The manuscript conveys a message that will be of use for the wide community of researchers working on mechanosensory integration and more broadly for engineers and scientists interested in using light to generate force. The study is extremely elegant, well written with beautiful illustrations. This work will be without a doubt a great addition to 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 #1 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

Maternal exposure to a certain phthalate (DEHP) has been shown to cause spermatogenesis defects in the male progeny, and in their offspring. In their paper, Tando et al have investigated the molecular consequences of this maternal exposure on fetal and adult male germ cells by studying DNA methylation and gene expression by large-scale approaches. They found three genes previously known to be involved in spermatogenesis that are deregulated following maternal exposure to DEHP and which could contribute to the observed spermatogenesis defects.

(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 multifaceted study focuses on neurons in the brain that produce a small peptide molecule known as GnRH, which is central to reproduction in its role as the releasing hormone for gonadotropins from the anterior pituitary. The findings will be of interest to scientists interested in the role of neuropeptides in determining normal brain function and the onset of neurodegenerative disorders. The authors provide a detailed anatomical and molecular characterization of a large, previously unnoticed population of GnRH neurons, located in basal ganglia (mainly putamen) in humans, which diverge from the population of GnRH neurons regulating the pituitary, in number (much larger), morphology and, possibly, origin (not from olfactory placode). Moreover, the study rekindles the idea that GnRH producing neurons in other regions of the brain outside the hypothalamus may be involved in neural processes unrelated to reproduction such as locomotion and decision making.

(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:

Lucas, Himes et al. present multiple practical improvements to the 2D high-resolution template-matching (2DTM) routine for cryo-EM images originally described by Rickgauer et al., eLife 2017. GPU-acceleration and integration into cisTEM make the approach substantially faster and easier to use than the previous CPU-based Matlab implementation. The strengths and weaknesses of the 2DTM are clearly presented and the comparison with 3DTM is thorough. At present the 2DTM approach is likely only suitable for analysis of large assemblies (e.g., ribosomes, proteasomes,etc.) in situ, but future improvements in microscope hardware and the 2DTM routine itself will likely allow application of this approach to smaller complexes.

(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.)

Evaluation Summary:

This paper is of interest for cell biologists studying mitochondrial fission as well as stem cell biologists studying neoplastic transformation. The work helps to clarify how variable levels of the master regulator of mitochondrial fission can have substantially different effects on gene regulation and mitochondrial network properties. A combination of complementary methods is used to support the key findings although aspects of data analysis and quantification 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:

This is an important and timely manuscript looking at excess mortality across 89 countries and territories over the course of the COVID-19 pandemic. This manuscript will be of interest to demographers and epidemiologists, and also more broadly to the public health community.

(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 names with the authors.)

Evaluation Summary:

This paper will be of interest to a diverse range of scientist as the questions span animal behavior, neuroscience and sex differences in brain-behavior relations. The study used non-invasive brain imaging to track large changes in structures involved in controlling communication between brain regions. The data reveal exciting sex-specific changes in key brain regions involved in learning and memory. The study is well designed, and the key claims of the manuscript appear to be well supported by the data. The imaging approaches employed are thoughtful and rigorous.

(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.)

Evaluation Summary:

This study could help shed light on mechanistic connections between latent infection by EBV with an age-dependent autoimmune condition, such as rheumatoid arthritis. The authors use two models: a murine model of rheumatoid arthritis (CIA), and a murine analog of human EBV: 𝜸HV68. The use of these two models allows the investigation of how latent viral infection exacerbates the autoimmune condition via the action of a special class of B cells: Age-associated B 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

The authors use dense electrode recordings in young mice and EEG recordings in human infants to quantitatively describe the transition from immature patterns of brain activity in sleep to more mature patterns. Interestingly, they find an intervening period when overall activity declines in both species. This study is interesting because it enriches our relatively impoverished view of how mature activity patterns emerge during development. However, reviewers expressed concerns that further work was need to rule out potential artifacts of the surgical and recording techniques used in the animal experiments.

(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 names with the authors.)

Evaluation Summary:

This manuscript describes their phase-targeted closed-loop auditory stimulation protocol to alter slow wave oscillations in rodents. This manuscript provides a set of proof-of-concept data for a rodent model of closed-loop auditory stimulation during sleep as a method for augmenting NREM sleep thalamocortical oscillations and its behavioral effect on a motor task. The strongest contribution of this study to the field is that it provides a technical basis for future studies to be carried out which actually explore the neurobiological underpinnings of CLAS in detail. Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent memory). It's also nice to have a non-invasive way to manipulate sleep, particularly to translate rodent research to clinical 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.)