Evaluated articles

Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway

1. Hyae Yon Kweon
2. Mi-Ni Lee
3. Max Dorfel
4. Seungwoon Seo
5. Leah Gottlieb
6. Thomas PaPazyan
7. Nina McTiernan
8. Rasmus Ree
9. David Bolton
10. Andrew Garcia
11. Michael Flory
12. Jonathan Crain
13. Alison Sebold
14. Scott Lyons
15. Ahmed Ismail
16. Elaine Marchi
17. Seong-keun Sonn
18. Se-Jin Jeong
19. Sejin Jeon
20. Shinyeong Ju
21. Simon J Conway
22. Taesoo Kim
23. Hyun-Seok Kim
24. Cheolju Lee
25. Tae-Young Roh
26. Thomas Arnesen
27. Ronen Marmorstein
28. Goo Taeg Oh
29. Gholson J Lyon

• Curated by eLife

  Evaluation Summary:

  This manuscript describes the identification of an animal model that reproduces several features presented in Ogden syndrome patients and reveals the roles of two N-terminal acetyltransferases in mouse development. It will be of interest to the readers in the field of protein acetylation and modification, and also to the scientific community involved in rare diseases and syndrome 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Feeding Experimentation Device version 3 (FED3): An open-source home-cage compatible device for measuring food intake and operant behavior

1. Bridget A. Matikainen-Ankney
2. Thomas Earnest
3. Mohamed Ali
4. Eric Casey
5. Amy K. Sutton
6. Alex Legaria
7. Kia Barclay
8. Laura B. Murdaugh
9. Makenzie R. Norris
10. Yu-Hsuan Chang
11. Katrina P. Nguyen
12. Eric Lin
13. Alex Reichenbach
14. Rachel E. Clarke
15. Romana Stark
16. Sineadh M. Conway
17. Filipe Carvalho
18. Ream Al-Hasani
19. Jordan G. McCall
20. Meaghan C. Creed
21. Victor Cazares
22. Matthew W. Buczynski
23. Michael J. Krashes
24. Zane Andrews
25. Alexxai V. Kravitz

• Curated by eLife

  Evaluation Summary:

  All three reviewers were very enthusiastic about this manuscript describing FED3, a new and improved open-source option for a home cage pellet dispensing device. They all agreed that this open-source tool would be of wide-interest to neuroscience laboratories, that the manuscript was well-written and clear, and that the cross-lab validation was informative. They also appreciated that this Tools & Resource manuscript all necessary open-source hardware, firmware, visualization code, and Arduino and Python libraries for user customization of experiments and analysis. Minor concerns were identified with the extent to which the manuscript describes and compares to existing systems and with clarity on some details of the system.

  (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.)

Reviewed by eLife

Seroconversion stages COVID19 into distinct pathophysiological states

1. Matthew D Galbraith
2. Kohl T Kinning
3. Kelly D Sullivan
4. Ryan Baxter
5. Paula Araya
6. Kimberly R Jordan
7. Seth Russell
8. Keith P Smith
9. Ross E Granrath
10. Jessica R Shaw
11. Monika Dzieciatkowska
12. Tusharkanti Ghosh
13. Andrew A Monte
14. Angelo D'Alessandro
15. Kirk C Hansen
16. Tellen D Benett
17. Elena WY Hsieh
18. Joaquín M Espinosa

• Curated by eLife

  Evaluation Summary:

  In this study, the authors use a systems immunology approach to document innate and adaptive immune responses during clincal SARS-CoV-2 infection. This general impact of this work is a better understanding of COVID19 pathobiology and more specifically, the identification of serum antibodies as a novel classification framework to understand COVID-19 disease course and associated changes.

  (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.)

Reviewed by eLife, ScreenIT

Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

1. Inés González-Calvo
2. Keerthana Iyer
3. Mélanie Carquin
4. Anouar Khayachi
5. Fernando A Giuliani
6. Séverine M Sigoillot
7. Jean Vincent
8. Martial Séveno
9. Maxime Veleanu
10. Sylvana Tahraoui
11. Mélanie Albert
12. Oana Vigy
13. Célia Bosso-Lefèvre
14. Yann Nadjar
15. Andréa Dumoulin
16. Antoine Triller
17. Jean-Louis Bessereau
18. Laure Rondi-Reig
19. Philippe Isope
20. Fekrije Selimi

• Curated by eLife

  Evaluation Summary:

  The reviewers agreed that this is a very interesting paper that demonstrates the involvement of a specific protein degradation pathway in a form of synaptic plasticity in the cerebellum. The strength of the work results from its innovative character. The authors show that SUSD4 is expressed throughout the brain and is abundant in cerebellar dendrites and spines. Mice with deletion of SUSD4 have motor coordination and learning deficits, along with impaired LTD induction. This study provides novel insight in the uncharacterized role of SUSD4 and provides a detailed and well-performed analysis of the Susd4 loss of function phenotype in the cerebellar circuit. The exact mechanism by which SUSD4 affects GluA2 levels remains unclear. However, their findings provide leads for further functional follow-up studies of SUSD4.

  (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.)

Reviewed by eLife

TRPM channels mediate learned pathogen avoidance following intestinal distention

1. Adam Filipowicz
2. Jonathan Lalsiamthara
3. Alejandro Aballay

• Curated by eLife

  Evaluation Summary:

  In this manuscript, the authors aim to address an important and interesting question: when an animal's intestine is colonized by pathogenic bacteria, how can it sense these bacteria and learn to avoid consuming them? Here the authors suggest that in C. elegans, sensing of intestinal distension or bloating caused by Gram-positive bacteria via intestinal ion channels may drive rapid behavioral responses through a process involving associative learning. While these findings are of broad interest to both the microbiology and neurobiology community, some of their conclusions are not currently fully supported by their data, and reasonable alternative interpretations exist.

  (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.)

Reviewed by eLife

Latrophilin GPCR signaling mediates synapse formation

1. Richard Sando
2. Thomas C Südhof

• Curated by eLife

  Evaluation Summary:

  The main finding that GPCR activity is necessary for latrophilins' role in synapse formation is both surprising and important. This work will inspire new research on compartmentalized GPCR signaling at the synapse.

  (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.)

Reviewed by eLife

Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons

1. Duc T. Nguyen
2. Destiny Berisha
3. Elisa Konofagou
4. Jacek P. Dmochowski

Reviewed by eLife

Conformational dynamics of auto-inhibition in the ER calcium sensor STIM1

1. Stijn van Dorp
2. Ruoyi Qiu
3. Ucheor B Choi
4. Minnie M Wu
5. Michelle Yen
6. Michael Kirmiz
7. Axel T Brunger
8. Richard S Lewis

• Curated by eLife

  Evaluation Summary:

  This study uses complementary approaches to advance our mechanistic understanding of STIM1 activation, with elegant single molecule methods providing new details on STIM1 structure and dynamics. Full length STIM1 in a cellular environment was probed by crosslinking, but the same has not yet been possible with single-molecule Förster resonance energy transfer (smFRET).

  (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.)

Reviewed by eLife

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay

1. Hiroaki Tachiwana
2. Mariko Dacher
3. Kazumitsu Maehara
4. Akihito Harada
5. Yosuke Seto
6. Ryohei Katayama
7. Yasuyuki Ohkawa
8. Hiroshi Kimura
9. Hitoshi Kurumizaka
10. Noriko Saitoh

• Curated by eLife

  Evaluation Summary:

  The method presented in this article is of interest for all fields that interface with chromatin dynamics. It could provide a powerful tool to dissect the mechanisms of chromatin assembly and disassembly genome-wide, and determine how cell cycle and chromatin structure influence these dynamics. However, in the current form, the article falls short of its potential. Further validation of the data, and clarification of its implications is requested.

  (This preprint has been reviewed by eLife. We include the public review from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Diverse inhibitory projections from the cerebellar interposed nucleus

1. Elena N Judd
2. Samantha M Lewis
3. Abigail L Person

• Curated by eLife

  Evaluation Summary:

  Judd and colleagues use a combination of mouse genetics and viral marking to expand the extra-cerebellar map of projections. These data will impact our understanding of how the cerebellum contributes to behavior and in general how brain function is packaged at the anatomical level. These data will not only impact cerebellar scientists but also those workers interested in how inter-regional brain connectivity is organized and how fine input-output circuit relationships are structured.

  (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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

The structure of behavioral variation within a genotype

1. Zachary Werkhoven
2. Alyssa Bravin
3. Kyobi Skutt-Kakaria
4. Pablo Reimers
5. Luisa F Pallares
6. Julien Ayroles
7. Benjamin L de Bivort

• Curated by eLife

  Summary: This manuscript is interesting to circuit-neurobiologists, behavioural biologists and psychologists. The reviewers agree that this manuscript addresses an important unanswered question: what is the covariation-structure in the vast space of behavioural variables that individuals can explore, and what defines their individuality in this space? The reviewers also praise the great efforts made in the experimental approach and analyses methods, which potentially will set new benchmarks in the field. However, the work can be improved, by accounting for the trial-to-trial variability in behavioural data and clearly distinguishing these from persistent idiosyncrasies observed in individuals.

Reviewed by eLife

Mapping the functional landscape of the receptor binding domain of T7 bacteriophage by deep mutational scanning

1. Phil Huss
2. Anthony Meger
3. Megan Leander
4. Kyle Nishikawa
5. Srivatsan Raman

Reviewed by eLife

Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers

1. Eduardo J. Fernandez-Perez
2. Braulio Muñoz
3. Denisse A. Bascuñan
4. Christian Peters
5. Nicolas O. Riffo-Lepe
6. Maria P. Espinoza
7. Peter J. Morgan
8. Caroline Filippi
9. Romain Bourboulou
10. Urmi Sengupta
11. Rakez Kayed
12. Jérôme Epsztein
13. Luis G. Aguayo

• Curated by eLife

  Summary: This study provides new information about how amyloid beta (Ab) oligomers (Abo) may contribute to hyperexcitability which is important because Abo and hyperexcitability have been suggested to occur early in the development of Alzheimer's disease (AD). The authors added Abo intracellularly (iAbo) using dialysis from a patch pipette. Their data suggest iAbo led to increased synaptic excitation mediated presynaptically by retrograde signalling of nitric oxide (NO). Furthermore, they present data suggesting that there is spread of this increase in excitation to neighboring neurons.

  Major Comments:

  1. The nature of the described effects of intracellular iAbo are quite unexpected, occurring within a minute of obtaining intracellular recording configuration, which contrasts with at least on previous study. While some controls for intracellular application of oligomers are provided, with reverse iAbo failing to reproduce the effect (Fig 2S1) and the effect being blocked by the antibody A11 (Fig 2S2), further controls are necessary to explain this rapid effect, which seems faster than that for the diffusion of the fluorescent tag into the cell (Fig 1S1). Note that Pusch and Neher (Pflug Arch 1988) determined diffusion time for different substances. That paper or others should be cited, and then some estimation of equilibrium time based on diffusibility of ab oligomers should be provided. Equations 17 and 18 in that paper provide some estimates based on molecular weight or diffusion coefficient. One point in Pusch and Neher is there is extreme variability between access times across cells and that it depends on access resistance, of course. Finally, the Pusch and Neher calculations were for small spherical cells - diffusion into spatially extended cells with long dendrites where the synapses are will take even longer. This is especially critical, as one of the major papers of precedent for this work is that of Ripoli, et al. 2014 (cited in the manuscript) in which the authors of that work examined effects of patch applied Ab42 over the course of 20 minutes, with internal controls showing differences between initial responses, right after break in, and 20 minutes later when the oligomer and/or monomers will have had a chance to equilibrate with the intracellular contents. It is not clear how such a rapid effect as indicated in the figures could be achieved by such a large molecule as Ab. The data suggest a time to effect of seconds to minutes, and the peak effect occurs before the fluorescence peaks, which seems hard to explain.

  2. The data need reorganization in terms of their results using h-iAbo or iAbo. There needs to be a clear demonstration of why both were used if the results are generalized with both (or not) and if they can actually use both interchangeably.

  3. The authors need to clearly indicate whether the experiments were done in culture or in slices. The authors need to provide a rationale on why specific experiments were done in culture and others in slices.

  4. There are aspects of the observed phenomenon that have not been taken adequately into account. For example, the authors have not investigated the effects of application of oligomeric beta-amyloid to either the extracellular space or the presynaptic neurons, two other compartments of the synapse.

  5. Aspects of the data raise questions: 1) Western blots appear to have multiple bands 2) evidence that the fluorescent probe accurately measures NO. 3) The bursts of activity are not quantified. What was defined as a burst? What was the burst frequency and did it change over the recording period? 4)The external solution for cultures contain 5.4 mM K+ which is quite high, and can induce hyperexcitability. Similarly, the use of 100uM AMPA and GABA seem very high. Justifying these high concentrations is important. They should lead to hyperexcitability and toxicity (AMPA) over time. Another point of concern is that the concentration of K+ for the slice work is 3 mM, much different than cultures. There are also differences in Mg2+ and Ca2+, making data hard to compare in the two preparations. 5) sample sizes are unclear 6) Intracellular Ab produces increases in both EPSCs and IPSCs. However, in Fig 3, the IPSC measures using a charge transfer quantification, did not show a significant change in response to iAbo, in contrast to EPSCs. 7) With regard to the inhibition, In the schematic on Fig. 10, I find this incomplete and slightly inaccurate since it shows one terminal releasing both glutamate and GABA with NO increasing both. While this is obviously an oversimplification, it's slightly inaccurate since NO was not directly shown to increase sIPSCs. Were NOS blockers able to disrupt the increase in sIPSCs? Moreover, there are many papers that have shown that PKC can also phosphorylate GABA receptors and increase their conductance. What could be the reason that this was not involved here? This needs to be discussed.

  6. How this work relates to other studies is necessary. For example, how this study is related to others about Ab exposure is lacking. Also, regarding hyperexcitability, many possible causes exist. These should be summarized in the introduction and the authors should comment how their results fit with these studies. Regarding PKC and NO, PKC and NO have several known actions throughout the brain and body. How do the effects the authors have identified relate to all these other effects? For example, if PKC is activated by another mechanism, would it occlude effects of Ab? What are the changes in PKC and NO in AD? Regarding the ability of the data to address AD, a major issue is whether the results are relevant to AD or represent interesting pharmacological data about what Ab can potentially do in some of its forms in normal tissue.

  Reviewer #2 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy

1. Tomasz Radaszkiewicz
2. Michaela Nosková
3. Kristína Gömöryová
4. Olga Vondálová Blanářová
5. Katarzyna Anna Radaszkiewicz
6. Markéta Picková
7. Ráchel Víchová
8. Tomáš Gybeľ
9. Karol Kaiser
10. Lucia Demková
11. Lucia Kučerová
12. Tomáš Bárta
13. David Potěšil
14. Zbyněk Zdráhal
15. Karel Souček
16. Vítězslav Bryja

• Curated by eLife

  Evaluation Summary:

  Radaszkiewicz and collaborators describe RNF43 as a novel negative regulator of WNT5A-induced signaling in human cells. They demonstrate that RNF43 can interact with proteins in this pathway, namely ROR1, ROR2, VANGL1 and VANGL2. Specifically, they find that, through these interactions, RNF43 can suppress invasive properties of melanoma cells, as well as the development of resistance to BRAF V600E inhibitor. The experiments are well done and well explained; however, they were performed only in an in vitro setting and with a very limited number of cell lines.

  (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.)

Reviewed by eLife

Voltage-clamp fluorometry analysis of structural rearrangements of ATP-gated channel P2X2 upon hyperpolarization

1. Rizki Tsari Andriani
2. Yoshihiro Kubo

• Curated by eLife

  Evaluation Summary:

  This study will be of broad interest to ion channel researchers interested in understanding the fundamental mechanisms of voltage-sensing. The researchers use a novel approach to determine the mechanism of voltage-sensing in a channel that lacks a canonical voltage-sensing domain.

  (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.)

Reviewed by eLife

A quadratic model captures the human V1 response to variations in chromatic direction and contrast

1. Michael A Barnett
2. Geoffrey K Aguirre
3. David Brainard

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to neuroscientists who study relationships between visual stimuli and their cortical representation, particularly, but not exclusively, those who use functional imaging techniques. The experiments are carefully designed, the dataset is substantial, and a model is presented that describes the data with very few parameters.

  (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.)

Reviewed by eLife

The mechanism underlying transient weakness in myotonia congenita

1. Jessica H Myers
2. Kirsten Denman
3. Chris DuPont
4. Ahmed A Hawash
5. Kevin R Novak
6. Andrew Koesters
7. Manfred Grabner
8. Anamika Dayal
9. Andrew A Voss
10. Mark M Rich

• Curated by eLife

  Evaluation Summary:

  Patients with myotonia congenita (or Becker disease) experience episodes of transient muscle weakness but the reasons underlying this phenomenon are unknown. This study provides the most definitive experimental evidence to date for the mechanistic basis of transient weakness in myotonia congenita and also suggests ranolazine may be beneficial for prophylactic management.

  (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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses

1. Stephan Wilmes
2. Polly-Anne Jeffrey
3. Jonathan Martinez-Fabregas
4. Maximillian Hafer
5. Paul K Fyfe
6. Elizabeth Pohler
7. Silvia Gaggero
8. Martín López-García
9. Grant Lythe
10. Charles Taylor
11. Thomas Guerrier
12. David Launay
13. Suman Mitra
14. Jacob Piehler
15. Carmen Molina-París
16. Ignacio Moraga

• Curated by eLife

  Evaluation Summary:

  This study is a great example of an elaborate combination of experimental and mathematical analyses to examine an intriguing, pleiotropic immunological signaling pathway. While a good number of individual aspects of this signaling pathway have been studied and reported before, the present work pieces together many pieces and succeeds to present a conclusive and comprehensive model of this particular cytokine system. The main conclusions are well supported by the presented data and the manuscript will be of interest and relevance for the study of many other cytokine signaling pathways, being of broad relevance for immunologists and cell biologists.

  (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.)

Reviewed by eLife

Synaptic plasticity regulated by phosphorylation of PSD-95 Serine 73 in dorsal CA1 is required for contextual fear extinction

1. Magdalena Ziółkowska
2. Malgorzata Borczyk
3. Agata Nowacka
4. Maria Nalberczak-Skóra
5. Małgorzata Alicja Śliwińska
6. Magdalena Robacha
7. Kacper Łukasiewicz
8. Anna Cały
9. Edyta Skonieczna
10. Kamil F. Tomaszewski
11. Tomasz Wójtowicz
12. Jakub Włodarczyk
13. Tytus Bernaś
14. Ahmad Salamian
15. Kasia Radwanska

• Curated by eLife

  Summary: This timely study provides important and novel findings with regard to the role of PSD-95 protein in fear extinction formation and helps to advance our understanding of how dendritic changes in the hippocampus regulates fear maintenance. The findings should appeal to those interested in hippocampal function, fear and fear-related conditions, and extinction-based therapies. The major strengths of the paper lie in the use of a wide range of complementary technical approaches, and the significance of addressing specific molecular mediators of fear attenuation. Reasonable alternative explanations were identified for some of the key findings and the conclusions may not perfectly reflect the observations and experimental designs.

  Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

APEX-Gold: A genetically-encoded particulate marker for robust 3D electron microscopy

1. James Rae
2. Charles Ferguson
3. Nicholas Ariotti
4. Richard I. Webb
5. Han-Hao Cheng
6. James L. Mead
7. Jamie Riches
8. Dominic J.B. Hunter
9. Nick Martel
10. Joanne Baltos
11. Arthur Christopoulos
12. Nicole S. Bryce
13. Maria Lastra Cagigas
14. Sachini Fonseka
15. Edna C. Hardeman
16. Peter W. Gunning
17. Yann Gambin
18. Thomas Hall
19. Robert G. Parton

• Curated by eLife

  Summary: The manuscript by Rae et al. reports a new protocol for labeling genetically-tagged proteins of interest with heavy atom particles for visualization by electron microscopy. The optimized protocol builds on the use of the enzyme APEX2, fused to the target protein of interest. The contrast enhancement may be useful in diverse 3D EM techniques. Also, reviewers were enthusiastic about the prospects for quantitative studies, even for low-levels of endogenous expression. Semi-quantitative studies may be enabled because the new method appears to improve the proportionality of the signal such that the number of APEX2 tags in a sample correlates with the number of heavy atom particles. The apparent simplicity of the protocol raises the potential for it to become a standard in the field of EM labeling.

  Reviewer #1, Reviewer #2 and Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife