Evaluated articles

Evaluation Summary:

The ribonucleoprotein YBX1 is required for sorting of miR-233 to exosomes. Here, the authors demonstrate that YBX1 undergoes liquid liquid phase separation (LLPS) both in vitro and in vivo and YBX1 droplets specifically partition miR-233 and mediate its packaging into exosomes. The authors also demonstrate a possible connection between YBX1 condensates and P-bodies during cargo sorting into EVs. Overall, this is an elegant study and with a few additional experiments to clarify the involvement of P bodies, the story will be of broad impact to those interested in LLPS and RNA packaging into exosomes.

(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 rigorous computational study simulates the sampling of the visual image by cone photoreceptors in the human eye, and explains how the image content can be reconstructed from those cone signals. The authors show that a number of properties of the human retina and of human perception are predicted from these simulations. The manuscript could be further improved by analysis of how these conclusions compare to those reached by alternate theoretical approaches, and by a consideration of human eye movements.

(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 manuscript has the potential to be of broad interest to scientists seeking to understand the evolutionary dynamics of plants during past periods of rapid climate change. Specifically, within the target genus of Cochlearia, the results indicate increased rates of speciation and diversification in response to pronounced glacial cycles. Future work to establish more direct mechanistic links between the results and conclusions will improve our understanding of adaptation and speciation.

(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:

Monitoring changes in pathogenic bacterial populations after bloodstream infection are poorly understood and in this work the authors develop new genetic analytic tools to dissect bacterial population dynamics at sites of infection. By harvesting bacteria from different sites and times of infection and performing deep sequencing to define the distribution of specific tagged-strains the authors provide a highly detailed snapshot of populations, with discriminatory power superior to prior studies. The work paves the way to future such studies in other organisms that cause persistent infection in humans.

(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:

In this study, the authors highlight a role for de novo biosynthesis of Poly-unsaturated Fatty Acids and the consequence effect of these metabolites on the production of arachidonic acid. The increased bio-availability of arachidonic acid seemingly promotes mycobacterial growth whilst inhibition of arachidonic acid formation, and its resultant downstream eicosanoid products, affect macrophage function but somewhat surprisingly do not affect growth of M. tuberculosis in macrophages or in mice. The uptake of the different classes of fatty acids in axenic culture as well as in macrophages is explored and the authors demonstrate that the Mce1 transporter is largely responsible for their uptake during in vitro growth but only plays a partial role in their uptake during growth of the pathogen in host cells. This work will be of interest to bacteriologists and those studying infectious diseases.

(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 by Piccolo and collaborators provides a general introduction to the common workflow language (CWL) with working examples taken from bioinformatics. The authors also introduce the ToolJig web application intended as a way of interactively creating CWL documents. This work should be of interest not only to beginner bioinformaticians but also to more experienced professionals that do not routinely make use of the latest developments in reproducible 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study demonstrates for the first time that the single annotated fucosyltransferase (TbFUT1) in the parasitic protist, Trypanosoma brucei is specifically targeted to the mitochondrion, rather than in the secretory pathway or cytoplasm, as in other eukaryotes. TbFUT1 utilizes glycan substrates in vitro and conditional down-regulation of TbFUT1 expression causes a severe growth defect in the two major developmental stages of these pathogens, indicating that it is essential for pathogenesis and a potential drug target.

(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 unexpected key finding is that T-cell-independent B cell activation engages the intracellular protein kinase PKC-delta to induce the necessary machinery of altered gene transcription culminating in IgG production. The methodology and the experimental setting are well-controlled, although how exactly B-cell stimulation by T-cell-independent antigens triggers PKC-delta remains to be elucidated.

(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:

Poly-ADP-ribosylation (poly-ADPr) is a major histone modification that plays critical roles in DNA damage. However careful mechanistic dissection of the role of poly-ADPr has been challenging as the modification is found on multiple proteins and there is heterogeneity in terms of poly-ADP-ribosylation chain length and amino acid location of attachment. The PARP1-dependent semi-synthetic strategy developed by the authors allows generation of nucleosomes with mono ADP ribose and defined lengths of poly-ADPr chains at specific histone serine residues. The utility of this method is clearly demonstrated by the authors' findings that ALC1, a chromatin remodeler that recognizes poly-ADPr is stimulated substantially by the presence of poly-ADPr on H2A and H3.

(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 paper presents a method for inferring the growth dynamics of bacteria from noisy single-cell data and applies this to C. glutamicum. Applying the method to experiments three phases of growth during the cell cycle are identified, including a dominant period of linear growth, which is interpreted in terms of a growth mode that is limited by polar cell wall synthesis.

(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 addresses the structural basis of the ability of fatty acyl-AMP ligases (FAAL) to exclude condensation of activated fatty acids with coenzyme-A and facilitate the reaction with other 4-phosphopantetheine linked acceptors. This issue is of significant interest with regard to understanding how certain fatty acids are channeled to specific metabolic fates. The structural question at hand is the apparent discrimination of the CoA moiety (adenosine 3',5'-bisphosphate) versus a holo-ACP tethered to the 4-phosphopantethein head group. This work will contribute significantly to our current knowledge of how distinct classes of enzymes divert fatty acids to virulent lipids in mycobacteria, and it will be more broadly of interest for metabolic engineering.

(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 study describes a novel algorithm to perform fully automated sleep staging in humans. It is well validated and performs at the level of other state of the art algorithms although it does not yet include comparisons against the existing tools available in the field. Given the efforts made by the authors to ensure ease of use and accessibility it may help extend the use of automated methods in the study of sleep.

(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 research will be of interest to neuroscientists who want to understand how visual systems are tuned to and encode natural scenes. It reports that rats share phenomenology with humans in sensitivity to spatial correlations in scenes. This work shows that an earlier paper's hypothesis about efficient coding may be broadly applicable, but it is perhaps most interesting in opening up the possibility of studying this sort of visual tuning in an animal where invasive techniques can be used to study this sensitivity and its development.

(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 find that long-range interhemispheric synapses are selectively weakened following loss of function of the gene mediating fragile X syndrome, the most common inherited form of intellectual disability. Using clever genetic and physiological approaches in mice, the authors show that the effect is cell autonomous and occurs postnatally by impeding the normal developmental strengthening of these synapses. The results convincingly enhance our understanding of the complex pathophysiology of neurological dysfunction in this developmental disorder.

(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 work serves as an independent confirmation and expansion of previous work, suggesting that certain domains in fungal adhesins can form amyloid-like structures that are essential for cell-cell aggregation, but less so for cell-surface adhesion or invasive growth. Specifically, the expression of different adhesin constructs offers insight into the functional role of the different adhesin domains. Together, the results provide further insight into the molecular mechanisms underlying fungal adhesion, which does only further our understanding of basic fungal physiology, but also offers insight into fungal pathogenesis.

(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 uses non-invasive imaging to look at the coupling within and between layers and regions of the human visual cortex during the modulation of attention. The results presented here are a re-analysis of a previously recorded dataset, but the novelty is the analytic technique used to relate laminar connectivity to rhythms. This in principle promises to advance the field of both oscillations and laminar fMRI and could deliver valuable insights. The work provides a non-invasive window on how feedback and feedforward circuitry in the human brain operates. We deem the work of potential interest to a broad audience as it aims to provide direct links between the animal invasive electrophysiology and human neuroimaging fields. However, in its current form, major reservations with respect to the hypothesis space being explored here as well as important analytic and technical caveats remain.

(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:

The authors performed a systematic literature review and meta-analysis to develop a dataset of respiratory viral loads (rVLs) for SARS-CoV-2. Focus was on finding the relation between individual case characteristics (e.g. disease severity, age and sex) and lower and upper respiratory tract viral loads. The study appears robust and comprehensive, and the results are valuable and contribute to the scientific knowledge in this 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:

Hülle cells, a type of cells formed by fungal species of the genus Aspergillus, are specialized cells that surround the sexual fruiting bodies of ascomycete fungi and are thought to nurse the fruiting bodies during fungal development. In this work, Liu et al. suggest that these cells have a strong ecological impact because they contain specific secondary metabolites that help the fungus to "withstand" the attack by fungivorous animals, like springtails, and also inhibit sexual reproduction of other fungi. This work will likely have a major impact on our view on the development and ecology of fungi as well as on the ecological functions of secondary metabolites.

(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 work will interest researchers who want to explore the functional potential in metagenomes. The authors present a new computational method, MetaGPA, for performing enrichment analysis on cohorts of metagenomes. They then use this approach to identify an enzyme that can modify cytosines in DNA from natural bacteriophage populations. Though successful, the approach needs to improve in clarity and methodology to be both reproducible and of broader impact, as claimed.

(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 will be of interest to neuroscientists in the fields of spinal motor control and spinal cord injury. The finding that silencing of spared lumbar to cervical long ascending propriospinal neurons after spinal cord injury enhances locomotor coordination is unexpected and well-supported by the data. This has potential implications for strategies aimed at promoting recovery of function after SCI.

(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.)