Evaluated articles

Evaluation Summary:

This is an interesting study describing the role of Samd14-capping protein (CP) complex in stress erythroid signaling. Using orthogonal cellular, biochemical and genetic complementation approaches, the authors provide evidence to establish a previously unrecognized mechanism for Samd14-CP interaction in regulating Kit signaling in erythroid regeneration in response to acute anemia. Findings of this work will be of broad interest to the study of erythropoiesis and cellular signaling.

(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 demonstrates that male mice lacking androglobin, a poorly understood heme-containing protein, are infertile and have defects in late stage spermatogenesis. A variety of molecular techniques were used to delineate the mechanism of spermatogenesis defect. A strength of the data is the identification of the androglobin interacting partner septin 10. With some clearer data on the mechanism underlying the connection between androglobin and septin, the paper will be of interest to researchers studying spermatogenesis.

(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 describes a female mosquito's behavior after a brief exposure to CO2, which has long been known to trigger host-seeking behaviour in female mosquitoes. The authors develop optogenetic tools in Aedes aegypti that enable the controlled delivery of 'fictive' CO2 to them. They show that a brief pulse of fictive CO2 alters the behavioral state of female mosquitoes, which lasts about 15 minutes. It provides new insights into how activation of CO2-sensing olfactory neurons alters the behavioral state of a mosquito towards sensory cues to increase host-seeking behaviors. The study will be of great value to the vector biology community, as well as to neurobiologists in general.

(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 explores the role of the central amygdala (CeA) on the mechanisms underlying chronic pain. An acid-induced muscle pain (AIMP) mouse model was used. The authors report a key pro-nociception role of CeA Somatostatin (SST) expressing neurons. The central sensitization of CeA-SST neurons was blocked by pregabalin. This work also further highlights the opposing view of the roles of CeA-SST neurons compared to CeA-PKCd neurons in modulating pain-related behaviors. This work will likely have a significant impact in the field and reconciles different previous results.

(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 provides new knowledge of one of the major molecules, claudin5, expected to maintain the integrity of the cell-cell contacts of the blood vessel wall. The results highlight organ and vessel-type specific significance of this mechanism in the regulation of vascular permeability, partially challenging the current view. A combination of in vivo microscopy and genetic mouse models is used to support the key claims in the paper. This manuscript will be of interest to scientists across vascular biology, and especially in the field of vascular permeability regulation.

(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 urban foresters, ecologists, and planners. It provides an urban tree dataset across US cities that can be used to address questions on urban biodiversity and ecosystem services. It contains clear descriptions about the data processing and structures in general, but would need further clarifications about the sample completeness and representativeness 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The authors explored the relationship between amyloid-beta and tau deposition and neural oscillations in Alzheimer's disease (AD) by using a computational neural mass model that can generate neurophysiological power spectra comparable to EEG- or MEG-like, macroscopic brain activity assessments. This analysis demonstrates the different, frequency-specific effects of amyloid-beta and tau proteins on excitation and inhibition, providing an integrated, multimodal explanation of the AD pathogenesis.

(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 interest to animal geneticists studying molecular breeding for infection resistance. The authors provide substantial new insight into the generation of a goat expressing domain fusion receptor TLR2-4, and clarify the mechanism to effectively eliminate S. aureus in macrophages from the gene-edited goat. Taken together, their findings suggest that TLR2-4 knock-in goats can serve as a good animal model for disease resistance breeding.

(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 is of interest to colleagues in immunity and signal transduction. Cytokines are small protein signaling molecules with a diverse range of activities in inflammation and immune system function. This manuscript reports the cryo-EM structure of the cytokine interleukin-27 (IL-27) bound to soluble domains of two receptor subunits, IL-27Rα and gp130. IL-27 is a composite cytokine consisting of the protein p28 bound to EBI3, which resembles soluble cytokine receptors such as the receptors for IL-6, IL-11 or CNTF. IL-27 signals predominantly via STAT1 and plays an important role in immune homeostasis. The data provide a detailed molecular view of how IL-27 binds to its receptor.

(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 a method to identify membrane proteins in native cell membranes based on a combination of single molecule AFM and an unsupervised clustering procedure to identify clusters of single-protein curves. This original approach represents a definitive step forward for AFM technology and methodology, which can generally only be used to characterize purified biomolecules of known identity. The work will be of interest to all students of membrane biology and especially membrane 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 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

This study measures the strength, timing, feature specificity and for the first time - spatial extent - of pre-saccadic processing of peripheral target information at the fovea, when fixation is not constrained. The authors conclude that saccade preparation causes feature-specific pre-saccadic visual enhancement restricted largely to the center of gaze. The manuscript is based on a rigorously curated dataset, it is well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and modelers. However, some key weaknesses in the interpretation of data were identified, which call into question the conclusion that the foveal enhancement observed can only be explained in terms of saccade preparation, thus weakening our ability to infer its mechanistic substrates.

(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 author present a large amount of sequencing data of EBV present in a variety of individuals, including a few with the interesting and unusual disease manifestation known as Chronic Active EBV (CAEV). The data show that there is a great deal of heterogeneity in the EBV genomes among people and overtime in some individuals, but the data do not reveal any particular mechanistic insights about the importance of this heterogeneity and the sample size is too small to warrant use of these deletions as therapeutic biomarkers.

(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:

Activation of NMDA receptors requires two co-agonists: Glutamate which binds to the GluN2 subunit and glycine/D-serine which binds to the GluN1 subunit. In the present manuscript, the authors address the interaction of D-serine, which is a less studied co-agonist than glycine, with the GluN1 and GluN2A subunits using molecular simulations as well as electrophysiology experiments. Surprisingly they find that D-serine interacts with the GluN2 subunit, further expanding our molecular understanding of NMDA receptor structure-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 names with the authors.)

Evaluation Summary:

The soluble membrane attack complex (sMAC) is generated from complement activation and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and vitronectin. Despite intense interest in sMAC, the mechanisms regulating its formation remain poorly understood. In this manuscript the authors demonstrate that sMAC is formed when complement is activated on bacteria that are resistant to killing by MAC pores.

(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:

Lupkin and McGinty studied gaze patterns in monkeys during value-based decision-making to determine whether relationships between gaze and choices that have been described in humans are also present in monkeys. Although previous literature has interpreted the effects of gaze on choice behavior to mean that attention to an option influences the decision that is made, a full understanding of the mechanisms underlying these biases will ultimately require data from non-human primates, making this an important and timely study. The authors use a clever task design to show that, as in humans, value-based choices are related to the amount of time spent viewing each option. The study is well-designed and the topic is significant to the field, but reviewers raised concerns about potential confounds and limitations not addressed by the current 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This work advances our understanding of the nuclear pore complex (NPC) biogenesis pathway by providing much needed additional insight into the function of one of the few NPC assembly factors, Brl1. It thus addresses a long-standing and fundamental question relevant to individuals interested in nuclear transport, nuclear cell biology, and membrane-protein interactions more generally.

(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 remarkably ambitious study that has been skilfully executed on a strong number of control participants, amputees, and one-handers. The complementarity of state-of-the-art uni- and multi-variate analyses are in the service of the research question, and the paper is clearly written. The main contribution of this paper, relative to previous studies, resides in the mapping of multiple face-part all at once in the three groups. The study suggests that the deprived hand cortical territory is not invaded by the facial cortical neighbor, the forehead, but instead by the lips that are more distant but functionally related to the hand as it can be used to compensate hand loss for manipulating objects.

(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 pathophysiology of Zika virus infection remains an area of high research interest. In this study, the authors use diverse experimental models to examine the potential role of Gas6 in Zika virus infection and associated neurological sequelae.

(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 reveals the contribution of intrinsic excitability to the formation of cortical neuronal ensembles. By combining optogenetic and electrophysiological approaches in vitro, the authors provide new insight regarding the role that plasticity of membrane excitability (intrinsic plasticity) plays in synaptic plasticity and the formation of memories.

(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 manuscript describes a metadynamics simulation-based characterization of the binding and unbinding dynamics of a buried phosphorylated residue in the inhibitory module to the functional domain of Vav1, in an effort to shed lights on the autoinhibition mechanism. The work led to a conformation-selection scenario of the event. The authors discussed the inconsistency between the computational findings and the NMR data, in terms of the free energy differences between the bound and unbound states. Further justification is required for the somewhat ad hoc choice of three collective variables for the metadynamics simulations, including two that are highly correlated.

(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.)