eLife

Latest preprint reviews

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

   This article has 10 authors:

   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

   This article has been curated by 1 group:

   • 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

2. Diverse inhibitory projections from the cerebellar interposed nucleus

   This article has 3 authors:

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

   This article has been curated by 1 group:

   • 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

3. The structure of behavioral variation within a genotype

   This article has 7 authors:

   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

   This article has been curated by 1 group:

   • 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

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

   This article has 5 authors:

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

   Reviewed by eLife

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

   This article has 13 authors:

   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

   This article has been curated by 1 group:

   • 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

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

   This article has 16 authors:

   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

   This article has been curated by 1 group:

   • 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

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

   This article has 2 authors:

   1. Rizki Tsari Andriani
   2. Yoshihiro Kubo

   This article has been curated by 1 group:

   • 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

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

   This article has 3 authors:

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

   This article has been curated by 1 group:

   • 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

9. The mechanism underlying transient weakness in myotonia congenita

   This article has 10 authors:

   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

   This article has been curated by 1 group:

   • 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

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

    This article has 16 authors:

    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

    This article has been curated by 1 group:

    • 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