Evaluated articles

Public Evaluation Summary:

Determining when cells acquire their individual identity is critical for understanding the patterning and growth of embryos. The authors use state-of-the-art methods to map the lineages of cells that emerge during the earliest stages of development in chick embryos and that contribute to the central and peripheral nervous system. The authors have characterised the gene signature of ectoderm sub-clusters and used algorithms to infer lineage trajectories using the dataset. However, the analysis of placode and neural crest emergence is not clear-cut or well supported by in vivo experiments in the embryo. The work overall will be of broad interest to developmental and stem cell biologists, as well as neurobiologists interested in the understanding of the neural and neural crest gene regulatory networks.

(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 paper, the authors use a mathematical model of plant and water dynamics in drylands to show that drylands adaptive capacity to respond to changes, via spatial self-organization in space, has also beneficial effects in preserving its biodiversity and ecosystem functions. The current study extends previous work by considering a trait diversity gradient that ranges from stress-tolerant to fast-growing plant species.

(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:

In this manuscript, the authors explore mechanisms involved in predation of other bacteria by Myxococcus xanthus. They identify two gene clusters, which encode proteins with homology to proteins of the Tad pilus system and some of which are important for predation. The work represents a good starting point for understanding how Myxococcus cells may engage in contact-dependent killing of other bacteria.

(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 names with the authors.)

Evaluation Summary:

This manuscript will be of interest to geneticists seeking to establish rules that govern gene regulation. To explain why a sequence enhances, rather than silences, gene transcription the authors draw our attention away from the binding of a single transcription factor, to focus instead on the number and diversity of transcription factor molecules that bind to it. Using a relatively simple metric called sequence information content they appear to be able to improve the prediction of enhancer over silencer sequences. A concern is whether the silencers are true silencers, or whether they only act as such in this specific experimental paradigm.

(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 potentially an interesting paper in which extensive MD simulations are used to probe the effect of phosphorylation of a tyrosine residue on the conformational ensemble of Ras GTPase. The insights form the basis for a screen of small molecule(s) that disrupt interaction with its target Raf kinase, and predictions are tested experimentally. Overall, the integrated approach is of interest to a wide range of biochemist and protein scientists and could potentially be used to modulate the activities of other 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. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This work describes the function of N6-methyladenosine (m6A) modification in developing retina. Enriched scRNA-seq and MeRIP-seq data will be an excellent resource for neurodevelopmental community.

(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 a comprehensive analysis of expression patterns and genomic features of long non-coding RNAs (lncRNAs) in the human developing gonad, using available single-cell RNA-seq datasets from both somatic and germ cells. Using multiple genetic strategies in an in vitro system of female germ cell differentiation, the study further shows a positive regulatory function of the LNC1845 lncRNA on its protein-coding neighbor LHX8, known to have a role in ovarian follicle development. This study has potential interest for reproductive biologists and for the non-coding RNA community.

(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 manuscript will interest a large community of molecular biologists studying translation and mRNA decay. The study provides a large-scale comparison of the roles of protein factors in No-Go Decay (NGD) and Codon-Optimality-Mediated Decay (COMD) in the yeast S. cerevisiae. A major strength of the manuscript is the direct comparison between one mRNA with a single strong translational stall and another similar mRNA with many slow translation sites (caused by changes in the genetic code). The analysis of both the factors that cause decay of these mRNAs as well as the ribosome states on the different mRNAs has the potential to reveal the molecular basis for the different mechanisms of mRNA quality 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:

The authors advance our understanding of the molecular underpinnings of allostery in GPCRs by showing the effects of allosteric modulators of mGluR2 on receptor conformation at distinct sites in the presence and absence of orthosteric modulators. This is important as drugs and drug candidates acting outside the site where the orthosteric or endogenous ligands bind are harder to identify. This work provides insights into allosteric changes at the level of individual receptors and provides a new path for drug discovery and is this of interest to colleagues studying GPCRs in health and disease.

(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:

The work describes the energetic constraints and preferred operating conditions of these "strategies" in particular on how nature has solved the problem of low energy "headroom'" required to prevent deleterious back reactions while maintaining efficient energy storage. The differences between the species are quite interesting and show that nature has evolved multiple solutions to fundamental limitations. Given the importance of understanding and improving the efficiency of photosynthesis, and the new insights revealed, the work will be of interest to a broad audience.

(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:

Menicucci et al. investigate the implication of sleep in the maintenance of ocular dominance plasticity in adult humans. This is an interesting study as it shows that sleep can maintain the changes in ocular dominance obtained after applying an eye-path on the dominant eye for two hours. This contrasts with the rapid decline of these changes during quiet wake in darkness. The authors further report correlations between sleep oscillations and the magnitude of the plasticity effect. These results highlight a possible implication of sleep in a new form of 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:

In this study, the role of different cortical areas on three distinct tasks all relying on the same virtual maze set-up was examined using optogenetic interventions and calcium imaging. The paper is potentially of interest to people interested in understanding the neural substrates of learning and how these can be impacted by previous knowledge and experience of stimuli. It could also be of use to behavioral neuroscientists when considering possible order effects of experiments.

(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 paper addresses a very notable gap that exists between evolutionary computing and experimental evolution. While artificial and computational approaches have long been used as an analogy for biological systems (with studies that have produced findings relevant for evolutionary theory), few studies have directly used methods and results from evolutionary computing to directly inform the shape and structure of experimental evolution studies. This study's approach is creative, and its approaches and results may be of use to both computational and experimental audiences. Lastly, this study can spawn future ones that draw even more connections between evolutionary computation/artificial life and evolutionary theory.

(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 manuscript probes the mechanism of postsynaptic retinoic acid (RA) signaling on presynaptic function. BDNF has important roles in synaptic plasticity, but how retrograde BDNF signaling is controlled following synaptic inactivity is unclear. The authors use genetic tools to localize the action of different components of the pathway to pre- or post-synaptic compartments and use biochemical approaches to define a molecular link between retinoic acid and local translation of distinct BDNF transcripts. The findings presented here fill a gap in our knowledge regarding how presynaptic function is adaptively modulated by BDNF by highlighting the role of RA in this process. The experiments have been well-executed and the data provide compelling support for the model proposed by the authors.

(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:

The authors report on the coordination mechanisms between oscillations recorded in the CA1 subfield of the hippocampus, prefrontal cortex, and olfactory bulb and cell ensemble activity in CA1 and prefrontal cortex that are associated with odor-cued decision making. The findings support the hypothesis that the beta rhythm plays a role in coordinating CA1-prefrontal cortex ensembles associated with an animal's accurate decisions. Sensory-guided decision-making is of broad significance to many readers who are studying executive functions and cognitive behaviors, and the observations reported in this manuscript provide insights into mechanisms that may support these functions and behaviors.

(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:

Houy and co-workers investigated the function of Munc13-1 and ubMunc13-2 in chromaffin cells and the interaction with phorbol esters (PMA). They combined calcium uncaging, capacitance measurements, amperometry, and activity-dependent movements of the EGFP-labeled Munc13 proteins. This study reveals that phorbolesters have a stimulatory effect via ubMunc13-2 but an inhibitory effect via Munc13-1. These opposing effects of the two Munc13 paralogs are surprising considering the closely related domain architectures.

(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 manuscript, the authors specifically look at the interaction between epidural stimulation of the spinal cord and the descending input evoked voluntarily in 2 intact monkeys. The results show that spinal stimulation could facilitate or suppress voluntarily evoked EMG and wrist torque, depending on voluntarily evoked activity as well as the stimulation parameters. This shows that spinal stimulation could enhance the descending inputs in cases of partial lesions. The conclusions of this paper are well supported by data, although they could be made stronger with additional analysis and clarification.

(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 manuscript will be of general interest to Drosophila researchers, whose work has long relied on the tools generated by the Gene Disruption Project (GDP). This manuscript provides a notable update on the work of the GDP. In it, the authors demonstrate the efficacy of new, streamlined transformation vectors, which they use to generate several hundred novel gene-specific Gal4 driver lines using CRISPR technology. The new vectors promise to allow the GDP to complete its goal of creating null mutations for every gene in the fly genome. The elegant functionality of the new vectors will also likely be of interest to workers outside of Drosophila.

(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 paper, which is of interest to membrane biologists and colleagues in signal transduction, examines the interesting question of whether LRRK2 recruitment to membranes may regulate its activity. Membrane association involves binding to membrane-tethered Rab GTPases via LRRK2's armadillo domain, and the authors propose an elegant feedforward mechanism to describe how recruitment could lead to Rab phosphorylation, but not all features of the feed-forward model are directly 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 manuscript by Fox, Birman, and Gardner combines human behavioral experiments with spatial attention manipulation and computational modeling (image-computable convolutional neural network models) to investigate the computational mechanisms that may underlie improvements in behavioral performance when deploying spatial attention. Through carefully controlled manipulations of computational architecture and parameters, the authors dissociate the effects of different tuning properties (e.g. tuning gain vs. tuning shifts) and conclude that increases in gain are the primary means by which attention improves behavioral performance. The analyses and results are technically sound and clearly presented, but the generality of the conclusions is limited by certain modeling/task choices made in the work.

(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.)