Evaluated articles

Evaluation Summary:

This study provides evidence that individuals with cerebellar degeneration show reduced effects of temporal expectation on perceptual discriminability with interval timing cues, but intact effects with rhythmic cues. The authors compare individuals with cerebellar degeneration to controls, and find a selective impairment of the individuals with cerebellar degeneration to use interval-based temporal predictions to facilitate visual discrimination, whereas rhythm-based performance benefits are spared. This study is of interest to psychologists and neuroscientists investigating prediction, perception, attention, and motor control, as it demonstrates a key role for the cerebellum in mediating the effects of interval-based temporal expectation on perception.

(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:

Acyl-homoserine lactone (AHL) based quorum sensing systems are an important form of intercellular communication in bacteria. These systems, minimally comprised of a synthase and a receptor, often involve different types of AHLs. This paper demonstrates that amino acids in the active site of the synthase and the binding site of the receptor have co-evolved to provide specificity for different signaling molecules, even though the synthase and receptor do not directly interact. This type of information could potentially be used to rationally engineer synthases and receptors with different specificities, as well as predict the specificities of uncharacterized synthases and receptors.

(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 paper reports a timely, computationally-inspired fMRI analysis of how hippocampus-dependent memory handles overlap in the timing and visual characteristics of objects we encounter. The findings speak to discrepancies in the field over how the hippocampus responds to similarity in memories and will be of broad interest to memory researchers and computational neuroscientists. The elegant experimental approach directly tests the predictions of a theoretical framework by parametrically manipulating visual overlap between associated stimuli. The analyses are clearly reported and directly address the hypothesis. The conclusions are sound. However, these findings may not yet generalize beyond visual similarity in the context of temporal co-occurrence or statistical learning, and some concern is raised over the theoretical groundwork for hippocampal subregion predictions and how context and overlap are considered in their memory network model.

(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:

Mosquito saliva can enhance transmission of arboviruses. Here, authors demonstrated that the anti-immune non-coding RNA from Dengue virus, known as the subgenomic flavivirus RNA (sfRNA), is secreted into mosquito saliva within the extracellular vesicles and can facilitate infection of the acceptor human cells when delivered together with infectious virus in mosquito saliva. The study potentially expands our understanding of flavivirus transmission.

(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:

Dravet syndrome, a severe seizure disorder resulting from a sodium channel mutation, is widely thought to result from impaired synaptic inhibition. Here the authors present multi-level evidence that excess synaptic excitation in the dentate gyrus is a locus of pathology. These results provide new insight into pathological mechanisms in Dravet syndrome that will be of interest to a broad range of neuroscientists studying epilepsy, as well as the role of the hippocampus and synaptic alterations in neurological 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper is of potential interest to an audience of DNA repair and cancer biologists because it seeks to refine the mechanism by which cells respond to DNA damage. By combining a number of genetic experiments based on cell survival of different mutant combinations and mutation analysis, their results support the view that Shu is critical for 3meC damage tolerance in yeast. Notably, expression of human ALKBH2, responsible for the repair of 3meC rescues the MMS-sensitivity of Shu mutants but not that of homologous recombination mutants. The study supports the existence of a new pathway for the removal of an important DNA lesion that seems essential in yeast, but likely contributes in other organisms, and helps clarify the distinctive role of homologous recombination in DSB repair and post-replicative repair. A few additional experiments are suggested to strengthen the mechanistic conclusions and better support the central model.

(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 manuscript endeavors to explain the mechanism of action of the gram-negative bacterial outer membrane TonB-dependent transporter BtuB, which acquires vitamin B12 from the external environment. The authors use electron paramagnetic resonance spectroscopy to monitor the proximity of different parts of this protein to one another during the binding of B12 directly in the E. coli outer membrane. This manuscript will be of interest to those who study the biophysics of membrane transporters and stresses the importance of studying membrane proteins in their native environment.

(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 manuscript combines cell biology, biochemistry, and quantitative biophysics to understand a new host cell factor, the human I-BAR domain protein IRSp53, promotes HIV type 1 (HIV-1) assembly and release. Since this new factor is a protein involved in the generation and sensing of negative membrane curvature, this manuscript will be of interest not only for retrovirologists and virologists in general but also for membrane biologists and biophysicists.

(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:

The authors found a mechanosensitive channel gene in T. cruzi, and aimed to characterize its functions. The authors provide conclusive evidence that TcMscS is a mechanosensitive channel. They also show that TcMscS has additional roles outside of mechanosensation, likely playing a role in the infectivity of T. cruzi.

(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 interesting genetics study shows that two well known tumor suppressor genes, ATR and Chk1, have a new function in sensing oxidative stress agents. The study is good quality and the results generally support the rather novel conclusions. It should be of interest in the fields of cancer genetics and cell biology.

(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:

The authors have highlighted an important aspect of epithelial maintenance in an environment that experiences significant biomechanical stress due to cardiac function. Using novel genetic models, detailed imaging and a thorough transcriptomic assessment, this story has the potential to enlighten both cell biologists and cardiovascular biologists on the underpinnings of myocardial integrity.

(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 paper will be of interest of neuroscience and ethology, as it bridges the gap between traditional and computational ethology by performing high-resolution imaging of muscle activity as an indicator of motor neuron activity, enabling the identification and analysis of behavior with computer algorithms. It also revealed the role of hormones in shaping and modifying the nervous system and animal behavior. The authors' major claims are supported by the data collected from thoughtfully designed animal experiments and computational analysis, although a few results can be interpreted better.

(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 reports a significant contribution towards an improved mechanistic understanding of light gated anion channels. The studies, which use the recently established method of in meso in situ serial data collection (IMISX), provide a basis for optimizing the anion channelrhodopsin GtACR1 from the alga Guillardia theta as a neuron-inhibiting optogenetics tool. The work will be of interest to anyone using optogenetics for functional studies. The reviewers had a few comments regarding technical aspects of 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. The reviewers remained anonymous to the authors)

Evaluation Summary:

This study could help shed light on mechanistic connections between latent infection by EBV with an age-dependent autoimmune condition, such as rheumatoid arthritis. The authors use two models: a murine model of rheumatoid arthritis (CIA), and a murine analog of human EBV: 𝜸HV68. The use of these two models allows the investigation of how latent viral infection exacerbates the autoimmune condition via the action of a special class of B cells: Age-associated B cells.

(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 lays the groundwork for a new level of precision in understanding mouse navigation behaviour by studying complex decisions that approximate those made in the wild, but can nevertheless be analysed with mathematically precise tools. Several exciting observations are made about navigation strategy. The manuscript will therefore be of broad interest across behavioural neuroscience. However, in its current form, some questions remain about some of the major claims.

(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 will be of interest to scientists interested in mechanistic studies of ion-coupled transporters. The authors demonstrate that dopamine, catecholamine and serotonin transporters - albeit structurally very similar - differ in the number of transport substrates and they define the underlying functional basis of this difference using a range of sophisticated techniques. This is an extremely nice and interesting study. providing new tools and new insights into an important class of transporter. Since many drugs that block one of the transporters also modify the two others, the paper may help to define pharmaceutical approaches that specifically block only one of them and that might allow for a better treatment of psychiatric diseases. The data analysis is rigorous and the conclusions are justified by the data, but the paper should be made more "user friendly" so that a wider audience could appreciate it better.

(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 advances our understanding of the Moody G-protein coupled receptor (GPCR) pathway in blood-brain barrier development, and describes a new role for protein kinase A (PKA) and two downstream signaling molecules in this process. It is not entirely surprising that PKA is involved, as it is downstream of many/most GPCRs, but the reciprocal localization and signaling relationship that the authors describe within subperineurial glia for Moody/PKA is very interesting. Generally, the data look very good, and the electron microscopy work is particularly nice. With some improved statistical analyses, this manuscript will make an interesting contribution to the field of neurodevelopment.

(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:

The objective of this study is to develop a novel immunofluorescence technique allowing for the multiplexed analysis of protein targets. This 4i method is an important technical advance will be of great interest for the scientific 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 be of interest to neuroscientists as well as a broad audience of cell biologists, as it provides new insight into the myriad of cellular functions regulated by the well-studied cAMP-dependent protein kinase, PKA. Rigorous biochemical data supports a model for PKA inactivation wherein dephosphorylation of the PKA regulatory subunit within a multiprotein complex leads to rapid capture of the PKA catalytic subunit limiting signaling duration. Overall, the biochemical data and modeling support the conclusions although a few details can be addressed further and the in vivo data remains preliminary. The work nevertheless presents exciting findings that provide a tantalizing mechanism to selectively modulate PKA activity at precise subcellular locations.

(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 is a comprehensive study of genomic and phenotypic diversity in the orphan crop quinoa. Based on whole genome resequencing of 310 accessions and field phenotyping of the same set of accessions for two years, the study identified the genetic basis of agronomically important traits. Based on this promising work, there will likely be scope for quick improvement of this orphan crop through 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 #2 and Reviewer #3 agreed to share their names with the authors.)