Evaluated articles

Evaluation Summary:

This manuscript is of broad interest to readers in the astrocyte and Alzheimer's Disease (AD) fields, and it utilizes state-of-the-art techniques to simultaneously record astrocyte calcium and animal behaviour. The work provides new insight into astrocyte calcium responses in AD, which has important implications for astrocyte pathophysiology. Overall, the data are of high quality and well analyzed.

(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 name with the authors.)

Evaluation Summary:

This manuscript is of particular interest to readers in the field of pain research. The identification of separate brain systems associated with learning from unexpected pain and learning from unexpected pain relief contributes to understanding of pain avoidance learning. The combination of behavioral data, neuroimaging and computational modeling provide support for many of the central claims of the paper, however weaknesses in the experimental design limit the support for the claims based on the results of the pharmacological manipulation.

(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:

Using a genome wide screen, the authors identify novel pathways that protect Pseudomonas aeruginosa against Type-6 secretion-mediated by other bacterial species. Importantly these pathways each protect against specific effectors. As an example, the authors further show that one factor Arc3B protects against phospholipase activity by antagonizing the production of lysophospholipids induced by phospholipase-type effectors. These findings uncover potentially conserved and unsuspected bacterial-defense pathways.

(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 describes how mitochondrial calcium in different regions of pyramidal neurons is controlled by action potentials and synaptic input. The authors show that calcium is controlled in a highly non-linear manner by calcium entry into cells (through voltage-dependent calcium channels) during sequences of action potentials. A particularly interesting finding is the high degree of localization of calcium rises in individual mitochondria in dendrites, and the requirement for both synaptic input and back-propagating action potentials to produce prominent rises of calcium in dendritic mitochondria. The work provides fundamental new information about how calcium entry during action potentials and synaptic input controls mitochondrial 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. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

RIF1 is a protein of the DNA damage response with key roles on genome integrity: it prevents DSB resection and hence accurate HR repair, whilst protecting stalled forks from degradation under replication stress conditions. The authors' main finding is the identification of 3 residues in RIF1 protein, that can be phosphorylated in ATM/ATR-dependent manner. However, this phosphorylation is dispensable for the ability of RIF1 to limit double-strand break resection, but is required to counteract the degradation of stalled replication intermediates mediated by the DNA2 nuclease. Therefore, the manuscript suggests that the three sites can provide a potential switch between the two functions of RIF1. These findings will spark the interest of readers working in the DNA replication and repair fields. However, the actual mechanism by which blocking RIF1 phosphorylation prevents RIF1 function at replication forks still needs to be determined.

(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 new work from Chen et al. reports on a critical question that is whether astrocytes can be converted in situ into dopaminergic neurons in response to the targeting of specific factors using, for example, gene therapy. This is a very strong, elegant and straightforward study. It is of broad interest and of high translational relevance.

(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 will be of interest to readers in the field of virus discovery. This study attempts to identify predictors of human-infective RNA virus discovery and predict high risk areas in a recent period in the United States, China and Africa using an ecological modelling framework. The study has potential to inform future discovery efforts for human-infective viruses . However it is not clear that key claims of the manuscript are currently fully supported.

(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 reports the first high-resolution structure of the P4 flippase ATP8B1, which is associated with intrahepatic cholestatic disorder in humans. Using biochemical studies guided by the structure, the authors demonstrate ATP8B1's autoinhibition mechanism, its regulation by lipids and phosphorylation, and a plausible mechanism of disease-associated mutation. These results are an important contribution to the expanding literature in membrane protein dynamics 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. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to researchers studying cardiac regeneration and regeneration in general. Given the multiple papers characterizing interstitial cell types during mammalian cardiac injury response, this type of characterization in one of the leading regeneration model systems is overdue. The authors utilize single cell sequencing approaches to identify dynamics and key features of interstitial cell populations during zebrafish cardiac regeneration, which largely supports the claims of the paper. The data presented here have the potential to serve as a valuable reference resource for future studies, although some of the conclusions, in particular those on the function of tal1 and mmp14, are not yet sufficiently supported by 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This work analyzes how meaningful connections develop in the nervous system. Studying the dissociated neuronal cultures, the authors find that the information processing connections develop after 5-10 days. The direction of the information flow is influenced by neuronal bursting properties: the early bursting neurons emerge as sources and late bursting neurons become sinks in the information flow.

(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 reports that ppGpp accumulation is necessary for acclimation to nitrogen starvation in a model plant Arabidopsis. The authors also showed a ppGpp-mediated downregulation of chloroplast gene transcription and a coordinated plastid-nuclear gene expression under nitrogen deficiency. This represents a solid new step in our understanding of plant responses to nitrogen-limiting conditions as well as on the role of ppGpp in plants and possibly throughout the green lineage.

(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:

The study presents novel results on spontaneous fluctuations in pupil dilation in relation to the spectral dynamics in a large sample of human participants. The study is based on MEG recordings allowing for quantifying these relations in time and space. The data provide important new insight into the temporal and spatial characteristics of pupil-linked changes in cortical states which form the basis for incorporating this insight in future clinical and cognitive neuroscience studies.

(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 name with the authors.)

Evaluation Summary:

This manuscript studies a topic of interest to developmental biologists using a combination of optogenetics, biophysical concepts, and mathematical modeling. How in plane contractile forces cause out of plane shape changes is a relevant open question, and the optogenetic tools developed in this work provide a new strategy to address the question.

(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.)

Evaluation Summary:

The possibility that local or systemic hypoxia regulates aspects of the immune system has attracted widespread interest over the last decade or more. Previous work has implicated regulatory T cells in at least some of these responses, and has demonstrated that over-activation of a specific hypoxia inducible factor (HIF) isoform, HIF-2alpha has the potential to driven pro-inflammatory lymphoproliferative responses characterized by defective regulatory T cells. The current work demonstrates that genetic activation of these hypoxia-signalling pathways that is restricted to the regulatory T cell lineage is sufficient to drive this type of immune activation. The work is important since it provides a focus for study of the mechanism, for which the authors make a proposal based on mis-localization of regulatory T cells. It is also important in focussing a key questions (requiring further study) as to whether physiological or pathological hypoxia, specifically affecting these cells, will drive such a response and/or whether the lymphoproliferative phenotype could be affected adversely or beneficially by agents that are being used to upregulate or downregulate hypoxia-signalling pathways in other settings.

(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 name with the authors.)

Evaluation Summary:

This study addresses the the potential effects of saturated vs. unsaturated fatty acids on kidney proximal tubule injury in diabetic kidney disease. They find that compared to saturated fatty acids, unsaturated fatty acids prevent ER stress by stimulating triacylglycerol formation.

(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 from Bishop et al aims to quantify the hypoxic and hyperoxic ventilatory response in the marmoset, an increasingly more common primate research model. The strongest contribution of the paper is the presentation of an analysis toolkit to perform unsupervised analyses of respiratory data, which are not widely available.

(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 intriguing study using cleverly designed stimuli to investigate the representation of physical stability in the human brain. This paper will be of interest to readers wondering when human cognition uses generalizable pattern matching similar to that used by machine learning algorithms, and when it relies on more specialized processes evolved for specific tasks. The well-crafted experiments generally support the authors' major claim.

(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.)

Evaluation Summary:

This manuscript describes the presence of two discernable populations of pancreatic delta cells in a zebrafish model. One of these subsets of delta cells is suggested to facilitate the regeneration of functional beta cell mass following beta cell ablation. This observation is of interest to investigators studying islet regeneration.

(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 a previous study the authors showed that the quorum sensing signal molecule 2-aminoacetophenone (2-AA) produced by Pseudomonas aeruginosa enables persistence in host tissue of this pathogen. They propose that this effect depends on a Warburg-like metabolic reprogramming effect in macrophages.

(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 is a fascinating article on the discovery of an unusual form of bacterial multicellularity: an organism that can exist in dense, filamentous multicellular structures and clusters of coccobacillus daughter cells. Experiments that mimic the periodic immersion that the bacteria experience in their natural cave environment suggest that water immersion plays a role in this life-cycle dynamics. This work, while rather qualitative, will nevertheless likely attract great interest from a diverse range of scientists working on multicellularity, the biophysics of cell packing, and geobiological problems.

(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.)