Evaluated articles

Evaluation Summary:

This paper will be of interest across psychology and ecology. It attempts to replicate influential findings that imply Theory of Mind in food-caching decisions of Eurasian Jays. The authors' approach to both attempting to expand on and replicate earlier findings is both rigorous and thoroughly contextualized. The failure to reproduce earlier findings raises important questions for 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This work presented in this manuscript paper may advance our understanding of an important class of anti-viral drugs (nucleoside analogs) that target polymerase enzymes by being directly incorporated into the product strand. This class of drugs is known to be quite diverse in their precise mechanisms of action, yet many of the particular details have remained elusive, often due to experimental limitations. The current study employs a single-molecule magnetic-tweezers platform to provide a new paradigm for the mechanism of drug remdesivir against the SARS-CoV-2 polymerase target. The authors propose that remdesivir does not prevent the complete viral RNA synthesis but causes an increase of polymerase pausing and back tracking. This paper is of broad interest to readers and scientists working on SARS-CoV-2 and general nucleotide inhibitors. The work includes the single molecule characterization of other NAs.

(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:

Hwang et al. address the important question about whether specific thalamic sub-regions serve as essential "hubs" for interconnecting diverse cognitive processes. Using a group of patients with isolated thalamic lesions (n=20), and a group of size-matched lesions outside the thalamus (n=42), they report that lesions to the anterior-medio-dorsal thalamus are most likely to cause widespread cognitive deficit. Evidence from existing task-based and resting-state fMRI data sets, as well as data sets on gene expression further provide evidence the importance of these regions as a network hub for domain general cognitive 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

How pollen apertures are formed is not well understood. By studying Arabidopsis mutants producing pollen with aberrant aperture numbers, the authors identify proteins from the ELMOD protein family as important regulators for aperture formation. They use genetics, transgenic constructs, and site-directed mutagenesis to pinpoint important residues for protein function in this process, and show that changes in expression levels of one protein can have dramatic effects on patterning. This paper will interest scientists interested in cell polarity, patterning, and evolution of diverse morphologies. This is also the first study of the ELMOD protein family, whose potential GTPase activating activities have not yet been investigated in plants.

(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:

Using single cell RNA seq, the authors characterize the sensory neuron microenvironment in dorsal root ganglia after sciatic nerve crush, dorsal root crush and dorsal column transection spinal cord injury 3 days after injury. The data revealed differentially expressed genes and pathways with sciatic nerve and dorsal root crushes co-clustering, whereas spinal cord injury largely co-clusters with uninjured. The results reveal influences of the tissue microenvironment and neuron extrinsic factors on axonal regeneration and also provide new insights into the role of PPARa signaling in regeneration after dorsal root crush. This is an impressive data collection effort across multiple cell types that will be of importance for generating new hypotheses in the field. The impact could be further broadened by increased attention to functional validation of the 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This is an interesting resource paper, describing the response of hematopoietic stem and progenitor cells to a few drugs commonly used to stress hematopoiesis. Transcriptomic analyses reveal interesting patterns, and the authors use ATAC-seq to investigate whether stem and progenitor subpopulations may be primed to respond in specific ways based on their chromatin accessibility. This turns out not to be the case when directly responsive genes are analyzed, and rather differences can be found in the promoter accessibility of genes further downstream.

(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 manuscript describes an analysis of cell type-specific alternative splicing using 10x scRNA-seq data. This work shows that in spite of the challenges associated with the analysis of such datasets, it is possible to identify alternative exons with differential splicing between tissue compartments and to some extent reveal cell types by splicing profiles of single cells. This work is informative regarding what can be done to analyse alternative splicing using 10X data and fills in a gap in 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper will be of broad interest to chemists and biologists studying complex coacervate systems, including biomolecular condensates. Its model provides a new way of obtaining diffusion properties inside and outside the condensates without the necessity of nontrivial assumptions. The model's capability is well presented by applying to experimental data and through further investigating the model through simulations.

(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:

Many algae, such as Chlamydomonas, form a pyrenoid under certain conditions to enable high photosynthetic rates during inorganic carbon limitation. The data presented here support that hydrogen peroxide, a common by-product of hyperoxia and CO2 limitation, induces pyrenoid formation in Chlamydomonas, even when CO2 levels are high. Although the underlying genetic mechanisms remain unresolved, these observations offer an exciting starting point to dissect the molecular components that drive pyrenoid formation. Therefore, this paper is of interest to a broad audience of scientists working in the areas of photosynthesis, synthetic biology of agriculture, and algal biotechnology.

(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 great interest to researchers interested in cognitive modulations of sensory processing as well as in the brain mechanisms of pain. It shows that attentional modulations of pain are associated with changes in neural communication between cortical areas, brainstem and spinal cord which are sensitive to opioidergic but not to noradrenergic modulations. These findings are conclusively supported by state-of-the-art simultaneous pharmacological fMRI of the brain and the spinal cord.

(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 proposes the identification of "bivalent chromatin" in genes associated with the biosynthesis of secondary metabolites in Arabidopsis and describes an investigation into the role of chromatin states in the regulation of the major Arabidopsis phytoalexin. Perturbation of either H3K27me3 or H3K18ac levels using mutants were used to show that there were effects on the expression of these metabolic genes. It has previously been shown that H3K27me3 and H3K18ac colocalize in the Arabidopsis genome and that genes targeted by PRC2/H3K27me3 in Arabidopsis are enriched for genes that respond to the environment and/or developmental cues. Therefore, the reported changes to the regulation of these genes in defective mutants are as expected, although the finding of this study will still be of interest to those working on pathogen-induced changes to plant metabolism.

(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 manuscript describes a very extensive set of experiments charting the origin and fate of various cell populations in the Drosophila ovary that is a powerful system to explore interactions between adult stem cells and their niches. The authors put forward a new view of how different cell types acquire their fates during development. This is a more nuanced view than extant models, involving common progenitors from which different cell fates (stem cell, progeny and niche cells) arise gradually and relying on spatiotemporal cues.

(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 manuscript provides an innovative merging of biophysical models with imaging data to explain the physical structure of microbial communities in the gut of zebrafish. Using imaging data to examine cluster sizes for eight different bacterial strains in the larval zebrafish gut, the authors report a common family of size distributions and show that these distributions arise naturally from a simple biophysical model of aggregation that tends to condense the system to a single massive cluster, reminiscent of gel formation observed in non-living systems. Within-host microbial dynamics represent an area of tremendous interest, as the microbiome is increasingly recognized to play a role in host physiology. This work contributes to a new perspective by elucidating physical mechanisms driving spatial segregation of these communities, opening the door to future studies that incorporate traditional genomic and microbiological insight with the physical and mechanical dynamics of microbial communities in living hosts.

(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 reports a methodologically rigorous investigation into the neural mechanisms supporting encoding and retrieval of specific and general information in the context of memory schemas for events, or "scripts." Its findings will be of general interest to neuroscientists and cognitive psychologists who work both with typical young adults (as studied int he present works) and in particular populations (e.g., development and/or aging; patients with brain damage). The work is particularly comprehensive in how it links both specific and general narrative representation at both encoding and retrieval with later memory behavior, which is a notable strength.

(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 by Wu et al., examined in a mouse model of Alzheimer how the lifespan and kinetics of both border-associated myeloid cells and microglia are affected. Taken together, these data provide evidence on the replenishment of CNS-associated myeloid cells under both steady-state and pathology.

(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:

Kaanders et al. investigate how the sampling of visual information by human subjects is biased toward their previous choice. The novel experiments and rigorous analyses largely support the presence of a 'confirmation bias' when information sampling is under the subjects' control. After ruling out some remaining alternative explanations of the observed behavior the paper will be of broad interest in cognitive neuroscience.

(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:

Nguyen et al. examine how helminth co-infection alters shedding from a respiratory bacterial infection (Bordetella bronchiseptica), fitting a model to data from experimentally infected rabbits to link the presence/absence of two helminth species with immune responses (neutrophil and two antibody classes) and bacterial shedding. The authors find a larger frequency of intense bacterial shedding-supershedding events-among helminth-infected rabbits, and model results suggest that triple infection may be associated with faster bacterial replication in the respiratory tract and more rapid shedding of bacteria. Linking immune responses with infection outcomes is of enormous practical interest, as is identifying why certain hosts are superspreaders, but there are some limits to what can be gained from this data set and model framework.

(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:

Koolschijn and colleagues present a novel and timely investigation of the balance between excitation and inhibition to explore the role of glutamate and GABA during memory retrieval. The innovative use of rapidly interleaved fMRI and fMRS provides a compelling link between successful retrieval effects in hippocampus and inhibitory/excitatory dynamics in visual cortex. The study itself is well-motivated and well executed, complementing prior cross-species work, and provides an intriguing set of results to support the major claims. This paper will be noteworthy to those interested in hippocampus-mediated cortical dynamics during memory retrieval. The rigorous methodology also demonstrates the utility of fMRS in investigating complex cognitive 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 #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This paper establishes a behavioural paradigm to study concepts developed in the field of economic decision making using the tractable model organisms C. elegans. It is therefore interesting to scientists studying the neuronal mechanisms of decision making and animal cognition.

(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 theoretical study by Ecker et al. designs a minimal yet biologically plausible spiking neural network model for hippocampal region CA3 in order to pinpoint the mechanistic sources of important features of population activity (namely sharp wave ripples and replay) observed in vivo. It reproduces many properties of these network events and offers explanations for the observed dynamics. In doing so it demonstrates that the synaptic connectivity patterns formed during spatial exploration may be crucial to the occurrence of these phenomena. The study will be of interest primarily to theoretical researchers because of the many innovative approaches fielded to design the network and analyse its dynamics, and potentially also to experimentalists investigating the hippocampus.

(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.)