Evaluated articles

Evaluation Summary:

This paper will be of significant interest to immunologists interested in understanding the determinants of antibody responses to vaccination. It uses tetramers to specifically identify and track CD4 T cell responses to influenza vaccination in younger and older adults, in an effort to understand why older individuals tend to have lower antibody responses to immunisation. The combination of tetramers, RNA sequencing and TCR clonotype tracking provides a powerful dataset to address fundamental questions of CD4 T cell immunology.

(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 conductance of CO2 into the chloroplast from the intercellular airspace is a key limitation to rates of net photosynthesis. Despite its importance, past work has been contradictory in what does and does not affect this mesophyll conductance. This paper takes a unique and multi-pronged approach to resolving the mechanisms of mesophyll conductance and proposing a transgenic approach for increasing it in C4 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This study presents evidence supporting population and sex-specific selection and an epistatic interaction between variants in the genes ADCY9 and CETP of pharmacogenetic importance. The confluence of evidence from population genetics, gene expression, functional experiments, and phenotypic association lends support to the paper's claims beyond what may be achieved by a single analysis. All three reviewers and I agreed that this work is of high interest in medical and population genetics and addresses a challenging topic in an impactful way.

(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 makes a connection between several proteins known to regulate endothelial function in pulmonary arteries, may be of interest to vascular, pulmonary and ion channel physiologists. The study provides compelling evidence that ATP released from pulmonary artery endothelial cell (EC) pannexin1 channels activates TRPV4 channels via an EC P2Y2R-PLC-DAG-PKC alpha pathway that is facilitated by the scaffolding protein Caveolin-1 and that this pathway helps to maintain low pulmonary vascular resistance and pulmonary artery pressure. Identification of this pathway provides new drug targets to improve pulmonary endothelial function in disease states such characterized by impaired endothelial function. What remains to be established or understood is the physiological stimulus for activation of the pannexin1 channels and ATP release and also the potential dark-side of overactivity of EC TRPV4 channels, which appear to have negative effects on EC 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 investigates the stability of the somatotopic organization of somatosensory cortex after spinal cord injury that results in tetraplegia. The findings suggest that somatotopic maps are preserved, degrading very slowly over decades, but that the amount of spared function is a poor predictor of somatotopic stability. These findings contribute to a developing story on how sensory representations are formed and maintained and has implications for the development of brain-machine interfaces for individuals with tetraplegia. The study is interesting and the manuscript is well-written. There remain concerns about some choices taken in the analyses.

(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 is a well-executed study describing multiple new findings related to the association between enhancer activity as measured by massively parallel reporter assay (MPRA), chromatin features, and underlying TF binding profiles in the context of different transcriptional states of cutaneous melanoma. There are several technical and conceptual advances including the refinement of MPRA assays and the understanding of regulatory mechanisms controlling cell state-specific enhancer activity that will be valuable for other investigators to adapt the experimental design and data analysis strategies. This work will be of broad interest to those seeking to understand cell type- or cell identify-specific gene regulation at the level of transcription and epigenetic control using these and related approaches.

(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 examined the mechanism underlying the development of prediction-error related responses of neurons in the primary visual cortex (V1) evoked by the mismatch between self-generated locomotor movement and visual feedback. The authors show that unilateral gene knockout of NMDA receptors or CaMKII in the primary visual cortex impaired the mismatch-related responses in V1. The experiments are well thought out and the paper is well presented. The results suggesting a role for local plasticity in V1 will be of great interest to those researchers interested in neural circuit development as well as cortical 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript presents a descriptive audit on statistically treatment, reporting and interpretation of the effects of sex as a biological variable (SABV) on the studied outcomes in articles published across nine scholarly disciplines. The manuscript highlights and provides data on prevalence of several inconsistencies and inaccuracies in the literature regarding treatment of SABV as an important moderator of the effects of an intervention on a considered outcome and how such inconsistencies could lead to biased conclusions regarding the effects of SABV. As such, the manuscript may inform not only funding agencies and grant reviewers, but also researchers in most scientific disciplines regarding the importance of adhering to rigorous methodological standards when examining the effects of SABV.

(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 describes the crystal structure of two key components of the autophagy system, the PI3P-binding protein WIPI2d in complex with its interaction region in the hATG8 E3 ligase scaffold component ATG16L1. The paper provides interesting new data and demonstrates the requirements for association of WIPI2d with membranes. Functional studies in cells provide evidence that mutation of residues at the interface for ATG16L1 binding affects function, although additional studies would support loss of function versus a dominant negative effect.

(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:

Wang et al. explores the relationship between the vigor of behavioral escape and cholecystokinin-expressing neurons in the premammillary nucleus of the hypothalamus that project to the periaqueductal gray. The experiments presented use a range of complementary approaches and techniques to perform a comprehensive examination of the circuitry underlying a particular aversively motivated behavior. However, a lack of clarity and specificity in how experiments and results are described, as well as a missed opportunity to relate this work to recent publications by many of the same authors, soften the conclusions that can be drawn from the manuscript in its current form.

(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 manuscript reports on two separate investigations. In the first, the authors provide novel evidence from two anaesthesia challenges that the slope of the 1/f structure of the power spectrum of the EEG fluctuates in a manner that tracks the presumed excitation : inhibition (E:I) balance of the tissue generating the EEG signal. Next they show that fluctuations in this slope also covary in systematic and modality- and stimulus-specific ways with behavioural performance on a multimodal attention task. These observations have potential foundational implications for how this previously unappreciated component of the EEG can be interpreted in terms of brain physiology and function. While the methodology employed is novel and interesting, the data as they stand, do not yet support the strong conclusions 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:

This report by LeClair et al. shows the importance of considering social dominance rank and history of winning/losing rank to define susceptibility to stress in mice. It has many strengths, including an elegant experimental design, including experiments in both males and females, and carefully considering two models of social defeat in females, and an excellent writing and representation 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Using a range of cutting-edge techniques, the authors of this manuscript explore the functional consequences of developmental changes in dendritic morphology and synapse distribution in a GABAergic interneuron. The experiments are carefully performed and represent a thorough investigation of the structural and functional changes in synaptic inputs and postsynaptic dendritic branching patterns, an important topic for both developmental neurobiologists and synaptic physiologists. The data support most conclusions, but alternative interpretations remain possible and should be further considered.

(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 reports careful work using auxin-mediated degradation to manipulate the DAF-2 insulin/IGF-1 receptor in specific tissues and at different ages of the nematode C. elegans. Since its initial discovery as a gene that could dramatically alter lifespan in this organism, daf-2 has been extensively studied. The authors make excellent and thorough use of their novel reagents to successfully add important new findings to our understanding of this broadly conserved aging pathway, including a finer dissection of the spatial and temporal requirements for DAF-2 in multiple processes, such as the decision window for entering dauer arrest and that altering the levels of this protein very late in life can still have dramatic effects on lifespan. Overall the data are convincing, but the presentation and clarity of the text could be improved.

(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:

Sleep serves vital functions for the body and particularly the brain, and accordingly these functions are impaired by sleep deprivation, as has been repeatedly shown for different cognitive processes. However, the neural mechanisms of such effects of sleep loss are still poorly understood. This manuscript is of interest to both sleep researchers and cognitive neuroscientists looking for insights into the effects of sleep deprivation across a broad range of methods and measures. The reported studies comprehensively investigate cortical excitability and plasticity with non-invasive brain stimulation, as well as electrophysiological markers and behavior. The studies confirm and extend previous findings, stating that, in general, sleep deprivation results in higher cortical excitability as well as a negative impact on 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Nordén et al. examine feather iridescent color diversity across bird species. Their findings show how key modifications in feather melanosomes, pivotal nanophotonic structures, underlie the brilliant colors of iridescent feathers, broadening feather color range approximately twofold. In a next step, the authors evaluate the function of feather melanosomes by performing optical modelling of nanostructure diversity, evaluating up to 4500 distinct nanostructure combinations, which are then contrasted with the observed (color) spectral data from 120 plumage regions across 80 (diverse) bird species. This meticulous integration of diverse methods across a comprehensive dataset will not only inform biologists studying structural color biodiversity, but it may also inspire engineers designing nanophotonic systems.

(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 the results of a model for cortical plasticity and resulting increase in neuronal responses to unexpected stimuli. This is an elegant study that provides a number of interesting, experimentally testable, hypotheses and develops a prediction for a mechanism for novelty response generation. However, a number of concerns were raised about the model, including how it relates to certain experimental data, that should be addressed.

(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 investigates the neural underpinnings of the bias property of timing, namely an overestimation for short and underestimation for long intervals, during an interval reproduction task in the medial prefrontal cortex of gerbils. The key novel result is that only neural populations with mixed responses, including ramping activity with linear increasing and slope-changing modulations as a function of reproduced durations, can encode the bias effect. Overall, experiment and data analysis are technically sound, and the conclusions are mostly well supported. However, the interpretation is too broad, and the manuscript would benefit of a more focused framing.

(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 reports on the synaptic impact of basal forebrain stimulation on a population of olfactory bulb interneurons in acute mouse brain slices. The author reveals that optogenetic stimulation of GABAergic basal forebrain afferents by and large inhibits the discharge of periglomerular cells, whereas cholinergic afferents evoke a prolonged, M1 receptor-mediated depolarization and increase in firing in a subpopulation of periglomerular cells. The current study would further our understanding of the olfactory neural circuit and how different co-released neurotransmitters shape postsynaptic neuronal responses.

(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 applies the framework of information theory to lectin-glycan signaling modulating the NF-kappaB response. The paper suggests that the information transfer capacity and information flow through the signaling pathway may be affected by a combined action of two distinct receptors having different distributions across a cell population, with possible implications for the immune response. The paper can have an impact on our understanding of signaling through multiple receptors converging on the same output, and will be of interest to experts in cellular signaling, particularly those with interest in innate immune response.

(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.)