Evaluated articles

Evaluation Summary:

The study shows that the LXRbeta - NCOR1 axis restricts the terminal differentiation of Treg cells into effector Tregs. It also suggests that, in addition to an impact on effector Treg differentiation, loss of NCOR1 leads to impaired suppression function in Treg cells. The results may contribute to our understanding of Treg cell differentiation and function.

(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:

There are various ways in which self-fertility has arisen in the fungal kingdom. This study describes a novel form of self-fertility that evolved in a species closely related to the Cryptococcus species causing serious human lung disease, in which sexual development is achieved by self signaling of a cognate pheromone and pheromone receptor pair. Through a combination of high-quality genomic analysis and experimental gene expression and manipulation work, the study adds to our understanding of the evolution and flexibility of fungal breeding systems. This work will be of interest to colleagues studying fungi as well as mating systems in any eukaryote.

(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:

The authors present a study on the cohesion maintenance of E.coli during collective migration in a self-generated gradient. They performed experiments and complemented the study with a predictive model and simulation to understand how bacteria with different phenotype are able to move as a cohesive group and how the individual bacterium defines its own position within the group. Particularly interesting aspects of the study are the use of titration of behavior with chemoreceptor abundance and the use of potential wells to model the attraction of bacteria to the center of their cohesive group. This approach will be of interest to physicists and biologists interested in collective motility and migration.

(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 the present study Pal and colleagues provide evidence that hydrogen sulfide (H2S) inhibits HIV replication and reactivation by a variety of mechanisms including inhibition of NF-kB and and recruitment of the epigenetic silencer, YY1, to the HIV promoter. They further report that H2S helps to maintaining mitochondrial bioenergetics and redox homeostasis and suggest that inclusion of an H2S donor in current ART regimens may help to achieve a functional HIV-1 cure.

(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:

The paper provides information about the relative importance of the type I and type III interferon-driven gene expression and anti-viral responses, particularly focused on the role of the Intestinal microbiota to maintain background levels of type III (interferon lambda) signaling. Type III-driven gene expression is highly discontinuous in the epithelial layer and mainly at the villous tips with consequent effects on the kinetics of rotavirus model infections.

(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 scientists who use imaging approaches to study cellular metabolism. It presents a new coarse-grained model for inferring mitochondrial NADH oxidation from NAD(P)H fluorescence lifetime imaging in mouse oocytes. The modeling is thoughtfully and clearly presented, but the validity of some key assumptions of the model and the overall generalizability of the method to other cell types could be strengthened.

(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 presents an integrated algorithm, based on several standard techniques in infectious disease epidemiology, to estimate the real-time reproductive number and show how it has evolved in different countries during COVID-19. However, the analyses should be modelled in a more integrated fashion. Uncertainty estimation requires more work. And additional data streams should be incorporated to more reliably capture infection 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Overall this study confirms that TNF-α is increased in peripheral blood B cells from PCOS and metformin decreased production. The study demonstrates the potential mechanism for the increase in TNF-α and reduction due to metformin. This is demonstrated in humans as well as in a mouse model of PCOS. Overall this is a well designed study demonstrating the impact of Metformin on immune function in PCOS.

(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 uses a combination of conditional knockout mouse embryos with targeted deletion of Elp1 in neural crest cells and neuron-specific antibodies to identify the onset of neural defects associated with the trigeminal ganglion. This manuscript is of potential interest to developmental biologists studying neurodevelopment disorders and, with additional quantification and experimentation, is likely to provide important insights into the mechanisms underlying Familial Dysautonomia in the cranial sensory ganglia.

(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 is of broad interest to cellular biologists and immunologists. It offers new insights into how T cell compartments are regulated in vivo defining a new perspective on how the T cell compartment is regulated to maintain immune homeostasis and afford long-term immune protection. By assessing data from a range of mouse model systems, the key deduction is that a simple hypothesis, one which notably does not have complex feedback regulation of cell numbers, provides a remarkably good explanation of the data.

(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:

The chemical sensing mechanisms of plants, which are largely unknown, are a topic of broad interest. The authors hypothesise that plant chemical receptors may be transporter proteins or odorant binding proteins analogous to those found in animals. The authors have identified a list of plant proteins with possible odorant binding activity and they predict binding constants for relevant odorants. The calculated binding constants are generally very weak in comparison to known animal odorant binding proteins (i.e., would require much higher concentrations of odor for detection). The in silico investigation, while inspiring, leaves many open questions, for example whether or not there is evidence for functional analogy between plant and animal odorant binding proteins.

(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 scientists within community ecology. The authors present a mathematically solid analysis of how nonlinear constraints influence resource-competition models with trade-offs, with the conclusions being similar to those of previous studies in which trade-offs are not exact.

(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:

The chromatin mark, H3K27me, is deposited by the Polycomb complex PRC2 and is associated with repressed genes. There are two important findings in this paper: 1) that the promoters of some H3K27me-repressed genes are regulated by nucleosome positioning and 2) the H3K27me repressed genes are a diverse group that can be derepressed by different mechanisms.

(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 will be of interest to scientists working on learning and memory and synaptic plasticity. It provides a useful overview of different forms of plasticity taking place in the learning and memory center of the fly, the mushroom body. The study mostly uses an acetylcholine sensor to image activity, which is novel and helps to tie together previous studies reporting memory-induced changes in calcium transients. In particular, the study highlights the compartmentalised plasticity along Kenyon cell axon terminals, the main cell type of the mushroom body. The current version of the manuscript could be improved by including some key issues: (1) behavioral experiments for the Cac knock-down experiments, (2) specific controls for some of the imaging experiments, (3) consideration of the role of dopaminergic neurons and (4) acknowledgment of the complexity of the mushroom body circuit and the literature that has addressed this previously.

(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 examined how mixture odors are represented in the mouse olfactory bulb. The authors found that compared to the responses in anesthetized mice, mixture responses are more linear in awake mice regardless whether the mice were engaged in a behavioral task or not. The results are potentially important as the results differ from previous studies which were done mostly in anesthetized animals, but the reviewers raised concerns for the validity and the strength of the 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 agreed to share their name with the authors.)

Evaluation Summary:

The study proposes that confined migration renders breast cancer cells resistant to apoptosis via NFkappaB-dependent mechanisms. The technical aspects of the study are impressive and experiments are very well performed and demonstrate the value of mimetic bioengineering approaches, but the postulated central premise would require more rigorous support.

(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 name with the authors.)

Evaluation Summary:

Catsburg et al. provide a new descriptive characterization of clathrin structures in spines vs dendrites using an excellent knock-in approach they recently developed. These results carefully validate earlier findings using the CRISPR approach and constitute useful baseline information, which would be useful in examining changes in the zone induced by neuronal activity or synaptic plasticity.

(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:

Presented here is a study on the role of cation chloride cotransporter CCC1 as a key regulator of the plant Trans-Golgi/Early Endosome trafficking network. While the work is well controlled and presented overall, the reviewers judged the data supporting localization of CCC1 to TGN/EE as not being sufficiently clear, as was the role of CCC1 in endocytosis, which is one of the main conclusions. These points can be clarified with future careful experimentation.

(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 will be of interest to readers in the field of anatomy and hippocampal physiology. The authors provide characterization of a novel projection pathway from layer 5a neurons in the MEC to CA1 of the hippocampus. They utilize cell specific viral labelling techniques, RNA-sequencing based projection mapping, and optogenetic aided in vitro physiology. The anatomical conclusions are well supported by the data. Future functional experiments will be necessary to establish the functional role of the projection.

(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 provides evidence that PEN1 and SYP122 regulate defense structures against filamentous pathogen infection including papillae formation and encasement of haustoria; this appears to be an ancient defense mechanism in land plants. If the findings that PEN1 and its close homolog SYP122 play an overlapping role in pre- and post-invasive immunity against cell-wall penetrating filamentous pathogens could be further validated, this would advance our understanding of callosic papilla/encasement-based nonhost defense mechanisms.

(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.)