Evaluated articles

Evaluation Summary:

This study will be of interest to virologists and those working on RNA-protein particles. Strauss and colleagues studied the mechanism of RNA recruitment to ribonucleoprotein condensates using rotavirus. Using multiplexed DNA-barcorded smFISH and DNA-PAINT for direct visualization of the RNP condensates in cells, they observe the early onset of viral transcript oligomerization before the formation of viroplasms and the process of enrichment in RNP condensates. They were able to image all eleven transcripts in an RNP condensate and to quantify the amounts of these transcripts. Based on these findings, the authors suggest a selective RNA enrichment mechanism of rotavirus. The experiments are nicely executed, with good controls.

(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 seeks to develop a mathematical framework for estimating rates of chromosome missegregation based on known chromosomal properties and observed aneuploidy rates. A derived model is validated using live-cell imaging before being applied to several previously-described datasets from tumors and organoids. The subject matter is of high interest to aneuploidy and genome evolution researchers.

(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 presents a theoretical analysis of the abundance of components of the translation machinery (ribosomes, initiation, elongation and release factors, tRNA synthetases) in bacteria. These proteins make up a large fraction of the total proteome and their abundance is closely linked to cell growth. That the stoichiometry of the different components is adjusted such as to maximize the growth rate has been postulated a long time ago, but was so far only studied in detail for ribosomes and EF-Tu, the most abundant elongation factor. Here, the authors extend these earlier works to an unprecedented level of detail and provide a complete analysis based on this idea and derive the optimal stoichiometry for all these factor, which they find to be in good agreement with the observed abundance in different bacteria. This provides new evidence supporting the idea of proteome optimization for maximal growth.

(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 explores the under-investigated role of mitochondrial activity and subcellular distribution for alveolar formation by using a variety of transgenic mouse models to delete two specific mitochondrial proteins. The data suggest a new concept for mitochondrial dysfunction driving lung injury and potentially human disease. With some further evidence to support the potential cell-specific role for the observed outcomes and additional mitochondrial assessment, this paper will be of interest to a large group of scientists interested in mitochondrial metabolism in general as well as lung development and disease in particular.

(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 study by Mika and colleagues uses a comparative transcriptomics approach to identify changes in the expression of genes that specifically occurred during the evolution of the human endometrium. The authors find that hundreds of genes gained or lost endometrial expression in the human lineage and that several of these genes are potentially implicated in the pathophysiology of human pregnancy. The study contributes to ongoing interest in the effect of human evolution on the pathophysiology of human pregnancy, and has the potential to serve as a model of how to study the evolution of pregnancy-associated genomic changes in particular species and tissues.

(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:

Human Herpesvirus 6A (HHV6A) and 6B are common herpesviruses that establish lifelong infection in latent form and can cause severe disease upon reactivation. They are spread by acquired infection of free virus and by germ-line transmission of inherited chromosomally-integrated HHV-6A/6B in telomeres. The authors develop an approach to analyse a hypervariable region of the HHV-6B genome and exploit it to investigate the relationship between acquired and inherited virus, presenting evidence that HHV-6B can readily transition between telomere-integrated and free virus forms.

(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 suggest that that intrinsically generated persistent firing activity of medial septal glutamatergic (VGluT2+) neurons underlies initiation of locomotor activity. In this work, the authors provide evidence for a non-canonical role for persistent firing in initiating locomotion by performing a series of technically difficult experiments to dissect the circuit mechanisms of the persistent firing. This manuscript will be of interest to readers in the field of spatial navigation, motor control, and neural network 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 #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

Strain variability in bacterial infections is a confounding factor in the treatment and prevention of the associated diseases. Pneumococcal disease is widespread, and the current vaccine targets only a subset of circulating strains, with disease and vaccine efficacy likely varying with the age of the host. Using two large databases of pneumococcal genomes, this study explores the associations between genomic factors and the age of the human host. Ultimately, these data and related studies will establish whether and how vaccines should be differentially designed for children and the elderly. This work will be of interest to those working in bacterial infections and host-pathogen genomics.

(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:

Non-nuclear genomes, such as those of mitochondria, contribute to many aspects of cellular function, organismal function, and fitness. Understanding their biology and evolutionary dynamics is thus an essential component eukaryotic evolution. The manuscript addresses an important and complex problem regarding the relationship between mitochondrial mutations, their impacts on gamete function, and the attendant evolutionary processes. The authors present a computational approach to distinguish between three hypotheses about the level of selection most likely to explain the distribution of mitochondrial mutations in human populations. They propose that selection among mitochondria is the most likely process to match empirical, clinical data, for mitochondrial mutation loads. There is, however, currently a mismatch between the fact that the data are derived from numerous different species whose biology is not always comparable, the model, and the title of 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. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

Bice et al. present new work using an optogenetics-based stimulation to test how this affects stroke recovery in mice. Namely, can they determine if contralateral stimulation of S1 would enhance or hinder recovery after a stroke? They found that stimulation of the cortex contralateral to the site of stroke impairs recovery from this stroke, and impairs the brain mapping and the connectivity that normally emerges in recovery from stroke. This unexpected finding in a mouse model relates to clinical literature on the role of the contralateral cortex in recovery.

(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:

Previous studies have indicated that neurons in different cortical areas have different intrinsic timescales. In this study, Pinto and colleagues aimed at establishing the functional significance of intrinsic timescales across cortical regions by performing optogenetic silencing of cortical areas in an evidence accumulation task in mice. The results are of broad interest, but the reviewers identified a few important issues that need to be addressed to validate the authors' conclusions.

(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 manuscript introduces a new tool - BigBrainWarp - which consolidates several of the tools used to analyse BigBrain into a single, easy to use and well documented tool. The BigBrain project produced the first open, high-resolution cell-scale histological atlas of a whole human brain. The tool presented here should make it easy for any researcher to use the wealth of information available in the BigBrain for the annotation of their own neuroimaging data. This is an important resource, with diverse tutorials demonstrating broad application.

(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:

The manuscript by Harper et al. examines the cancer risk perceptions, provider communication behaviors and demographic factors influencing the uptake of both, cervical and colorectal cancer screening among 50- to 65-years-old women. Towards those goals, the authors adapted and administered behavioral questions from the Health Information National Trends Survey to a multiethnic population sample in Southeast Michigan. Self-reported cancer screenings for the tumors (as defined by the USPSTF updated guidelines) served as the variable outcome. The study has public health merit in its identification of distinct predictors for cervical cancer and colorectal cancer screenings. The insights from this work on screening behavior differences among women, the perception of cancer risks and impact of positive provider communication, point to the need for exploring new ways for more holistic and integrated cancer prevention with a targeted focus. The strengths of the study include (i) the identification of an unmet need in public health in a neglected patient population, (ii) the track-record of the seasoned investigators, and (iii) the recognition of two potentially actionable insights obtained from the study. Weaknesses of the work include (i) the descriptive and specialized nature of the manuscript, (ii) the regional setting of the study and the question of how generalizable their conclusions would be in other contexts, and (iii) the relatively incremental advance of the reported findings.

(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 interest and relevance to clinicians and researchers in the field of muscular dystrophy, a condition that causes loss of muscle function and mobility primarily in older patients. The presented experiments suggest that at least part of the pathology of DM2, a certain form of muscular dystrophy, is caused by defects in a gene that is required for the production of small molecules, called polyamines which are known to support muscle health and function. Interestingly, in a Drosophila model of DM2, feeding with polyamines can restore muscle function. The paper gains broad interest by the demonstration that consistent with the findings in Drosophila, muscle biopsies from human DM2 patients show decreased ODC and polyamine levels, raising the possibility of using polyamines for therapy or prevention.

(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:

How the bacterium E.coli decides when to divide is an interesting, important, unsolved and highly controversial topic of interest to readers across disciplines, including microbiology, cell biology and statistical physics. Popular "single process" models invoke regulation at the step of replication initiation or at the step of cell division per se, whereas these authors have previously proposed a "concurrent cycles" model in which both processes are relevant, with different prominences in different situations. Consistent with the authors' motivating hypothesis, in the particular perturbed condition investigated in this work, a process different from DNA replication becomes increasingly important for division control as the degree of perturbation increases, which provides a new challenge to models for cell division control.

(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 names with the authors.)

Evaluation Summary:

This paper addresses researchers interested in architecture and function of the insect central complex as it represents the first comprehensive projectome dataset of any central complex outside Drosophila. The authors use the bumblebee as representative for hymenopterans with their navigation skills. Further, they mine their data for conserved and diverged aspects compared to fly (Drosophila) knowledge and hypothesize how the differences may relate to diverged neural circuit function. Hence, they provide an excellent and comprehensive descriptive resource providing a point of reference for others and a starting point for comparative studies of neural circuits. In particular, this study is the first comprehensive description of columnar neurons in the bumblebee central complex, described through the lens of the recently published fruit fly connectome of the same, homologous neuropil. The comparative approach used here holds promise for describing neural circuits in bees and flies in shared frame of reference. The authors use an approach that reflects a compromise between quick collection of electron microscopy (EM) data and being able to fully reconstruct all neurons in the bumble bee's central complex. The authors are transparent about the method's limitations and draw appropriate conclusions.

(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:

In this rigorously conducted meta-analytic study, the authors investigated the functional and structural abnormalities associated with developmental dyslexia across languages. Convergent and divergent functional and structural changes as well as language-universal and language-specific brain alternations related to dyslexia are found. In general, the study has generated important results and the findings are of interest to readers in educational psychology/neuroscience fields, especially those focusing on reading development and dyslexia. The analytic approach used in this study is cutting-edge, the data support the main claims, and a detailed discussion is 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:

Bacterial ParB partition proteins have the novel property that they employ an unusual nucleotide cofactor for complex assembly at their specific DNA binding site, parS. The impact of this study is on our general understanding of this novel class of nucleotide-dependent processes, and the role that nucleotide-protein interactions play in DNA binding and bacterial physiology.

(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 interesting, timely and well-done study focuses on the mechanism underlying nevus growth arrest, which has received renewed attention as a result of recent studies that question the dogma that such arrest is mediated by oncogene-induced senescence. Through experiments involving both cultured primary human melanocytes and cells derived from clinical samples, the authors show that Braf-oncogene-induced nevus cell growth arrest results from microRNA-dependent suppression of the mitotic kinase Aurkb, which influences whether Braf activity is proliferative versus antiproliferative. While the conclusions made within the manuscript are justified, and there is sound acknowledgment of certain pitfalls that could be addressed in future research, more expansive sample sizes and further in vivo work would aid in providing more clinical relevance. This manuscript would appeal to researchers in the melanoma field, especially those studying the underlying mechanisms behind phenotypic plasticity and tumor heterogeneity.

(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 provides an experimental and computational method for the identification and reconstruction of full-length circRNAs using nanopore sequencing,. With a better comparison to other existing methods in the field and a clearer demonstration of the advantages of the described methodology, the work would be of great interest to researchers in the circular RNA 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 #3 agreed to share their name with the authors.)