Evaluated articles

Evaluation Summary:

This manuscript investigates the consequences of Disrupted-in-schizophrenia-1 (Disc1) gene knock out in the medial prefrontal cortex (mPFC) of mice. This work marks a potentially significant contribution to elucidate cortical circuits alterations in this genetic model of schizophrenia. The main message is that communication between cortical pyramidal neurons and fast spiking interneurons is altered with consequence on cortical network activities. The data generally support the conclusions made but analyses of electrophysiological data should improve.

(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 is of relevance to the field of DNA repair. It uses a cleverly designed new recombination assay in yeast to address the impact of DNA break position on global genome mobility. A centromere-proximal DNA double-strand break (DSB) induces an H2A(X) phosphorylation-dependent global mobility that accelerates but is not essential for DSB repair, while a centromere-distal DSB triggers global mobility that is essential for repair and which depends on H2A(X) phosphorylation, Rad9 and Rad51. Together, these data support a model where global genome mobility promotes homologous recombination repair, particularly for centromere-distal DSBs, and help settle some recent controversy 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. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper is potentially of broad interest to researchers in the chromosome biology field. With specific loading sequences identified, the condensin DC complex studied here provides an elegant system to investigate the in vivo activities of SMC complexes. Combining Hi-C, ChIP-seq and RNA-seq, the authors have a comprehensive suite of assays to probe their questions. However, not all of their major conclusions are currently supported by 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Mechanisms for controlling gene dosage and uniparental gene expression vary widely across the eukaryotic tree, with many such mechanisms still unknown. Montgomery et al. describe an epigenetic mechanism used to modulate paternal chromosome gene dosage during the transient diploid state of the primarily haploid plant, Marchantia polymorpha. This fascinating case of genome-wide genomic imprinting will be of broad interest to evolutionary biologists, epigeneticists, and those focused on understanding the context and mechanisms of gene dosage 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This report identified NK-extracellular-vesicle (NK-EV)-associated microRNAs and characterized them by small RNA next-generation sequencing. They found that NK-EVs promote Th1 polarization and activation of monocyte and monocyte-derived dendritic cells. The findings are potentially important for understanding NK cell 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

The authors set out to investigate the roles of SMAD4 and TGFbeta in regulating memory CD8 T cell differentiation during viral infection. To achieve their goal, the authors utilized a variety of available tools including, gene expression, mice that lack certain regulatory genes, and different tissue tissue culture approaches. Although the in vitro experiments yielded interesting results that will interest students of T cell immunology/biology, there is an absence of results from in vivo studies that would validate the in vitro observations.

(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 outstanding manuscript evaluating a mutation commonly seen in AML and MDS in a spliceosome protein called SF3B1. The authors link this spliceosome mutation to altered transcripts and ultimately to cell cycle proteins and differentiation. This paper will be of high interest for oncologists in that it demonstrates that AML and MDS cells with this mutation can be targeted in a precision medicine approach.

(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 provides important new information regarding the functions and behavior of lung tissue-resident alveolar macrophages in the context of acute lung injury. New data regarding the impact of hypoxia via HIF-1 on biology of these critical cells are provided and importantly suggesting an impact on the outcome of lung injury.

(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 presents an artificial neuronal network which, from action and visual inputs, develops representations of space comparable to those found in the navigational system of the brain. They show that the representations developed by this network can be used in novel environments and in a reinforcement learning task. This demonstration of representations in absolute coordinates from agent-centered information is a significant contribution to neuroscientists as well as machine learning.

(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 is of interest to readers interested in how brain gene expression patterns differ between humans and other animals. The authors develop an innovative approach to map correspondences between the gene expression profiles of human and mouse brains, finding that the profiles of sensorimotor areas are more similar than those of transmodal association cortex. This thus contributes to our understanding of the genetic mechanisms that may drive differences in brain organization across species. The study is methodologically sound and the key claims are supported by 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Berryer et al. report on an automated and quantitative platform to study the number of synaptic inputs formed in networks of human excitatory neurons and astrocytes in vitro. The authors tested the utility of the platform by screening a large collection of small molecules and identified several modulators of synapse density, which were validated in follow-up experiments. The automated platform substantially extends what is currently available, particularly with respect to the automation of the initial analysis steps. The positive hits identified here, the inhibitors of bromodomain and extraterminal (BET) family of gene expression regulators, are important, and will likely contribute to the understanding of the mechanisms of human synapse assembly.

(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:

This paper will be of interest to neurobiologists and developmental biologists. Identifying novel mechanisms that prevent excessive neuronal migration is an important contribution to the field of neural development. The key conclusions of the paper are well supported by 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

The authors found elevated Hsp 27 levels in brains from Alzheimer disease patients. Hsp27 co-localized with p-Tau, efficiently prevented pTau fibrillation in vitro, and mitigated neuropathology of pTau aggregation in a Drosophila tauopathy model. A series of biochemical assays is presented to supporrt the claim that Hsp27 prevents abnormal Tau aggregation and p-Tau pathology. Overall, the study is well designed and presented, and the data convincingly support this major conclusion, which is relevant to colleagues studying neurodegeneration.

(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:

Pond et al. established a 2D patient-derived organoid screening platform to study tissue patterning and kinase pathway dynamics. They aim to understand how the spacing of different colonic cell types and their communication are regulated. They found that apoptosis induces Erk signaling waves that prime cell movement and are essential to maintain tissue patterning in the organoid monolayers. The work presented here is of importance to the field and provides insights into how Erk waves driven by apoptosis can help maintain gut homeostasis.

(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 article introduces "DetecDiv", a high throughput, deep learning method to perform automated cell-division tracking in yeast. The performance of the method, estimated to be 100 times faster than manual annotation, overcomes current time processing limitations that are inherent to large single cell datasets. In particular, DetecDiv allows to automatically get quantitative measurements of replicative life span in yeast. The method is of broad interest for quantitative biology as it can be used to study yeast cells dynamics across their lifespan.

(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 study asks how diverse signals are integrated at the cellular level to generate adaptive behaviors. The authors show that prolonged food deprivation (i.e. fasting) of C. elegans broadly alters gene expression in food sensing neurons, thereby altering foraging behavior and chemosensory neuron responses to food. The fasting-induced genes include many chemoreceptors, one of which mediates responses to specific volatile components of food. Finally, they show that food controls the expression of a fasting-induced chemoreceptor via multiple external (i.e. sensory) and internal (potentially metabolic) cues. The paper is of importance to scientists with an interest in adaptive behaviour as well as the cellular and molecular mechanisms underlying integration of stimuli.

(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, which will be of interest to basic scientists and clinicians in the fields of dental and craniofacial malformations, explores the validity and usefulness of mouse teeth as a model for studying the role of enhancers in human dental development and disease, based on a multi-layered integrated analysis of genetic data with different available data from mice and humans. The results from the study can provide a useful tool for the manipulation of expression of reporter or other genes in a tooth- or enamel-specific manner.

(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 web-based software developed in this study will be of interest to researchers who develop CRISPR-based diagnostic methods. The use of CRISPR-Cas to rapidly identify specific mutations in both cancer and infection is an evolving field with good potential to play a role in future research and diagnostics. This software will facilitate the implementation of such technologies and is therefore useful.

(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 manuscript builds on previous work to design yeast display libraries representing full viral proteomes with overlapping 15-mer peptides binding to specific HLA-DR alleles, and therefore potentially immunogenic for CD4 T cell responses. The authors use SARS-CoV-2 and dengue viruses as proof of concept and identify a number of potentially immunogenic peptides not predicted by current algorithms. The methods are interesting and promising and will be of interest to a wide range of researchers in immunological and infectious disease 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 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of interest to scientists interested in intergenerational transmission of phenotypes through genetic pathways. The authors propose an innovative and sound method to leverage the adoption of a design for disentangling prenatal and postnatal genetic effects. Additional analyses are needed to address the limitations of the model applied to the specific dataset that was used to illustrate the method.

(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.)