Evaluated articles

Continuous psychophysics shows millisecond-scale visual processing delays are faithfully preserved in movement dynamics

1. Johannes Burge
2. Lawrence K. Cormack

• Curated by eLife

  Summary: All three reviewers agreed that the paper lacked new biological insights. Two reviewers also raised concerns about the very low number of participants. The novelty of the task is also somewhat overstated; using tracking with different displays and varying luminance to each eye is certainly novel and enterprising, but visuomotor tracking per se is not novel, as pointed out by the reviewers.

  That said, all reviewers found that the manuscript presented an interesting way to study this system, and the methods are promising given the careful and thorough recapitulation of previous results using this technique. The paper is well written, and the application of the tracking method to this specific question interesting. Reviewer #1 raised a number of subtle but not insurmountable technical issues.

Reviewed by eLife

Identification of Gli1 as a progenitor cell marker for meniscus development and injury repair

1. Yulong Wei
2. Hao Sun
3. Tao Gui
4. Lutian Yao
5. Leilei Zhong
6. Wei Yu
7. Su-Jin Heo
8. Lin Han
9. X. Sherry Liu
10. Yejia Zhang
11. Eiki Koyama
12. Fanxin Long
13. Miltiadis Zgonis
14. Robert L Mauck
15. Jaimo Ahn
16. Ling Qin

Reviewed by eLife

Migration without interbreeding: Evolutionary history of a highly selfing Mediterranean grass inferred from whole genomes

1. Christoph Stritt
2. Elena L. Gimmi
3. Michele Wyler
4. Abdelmonaim H. Bakali
5. Aleksandra Skalska
6. Robert Hasterok
7. Luis A. J. Mur
8. Nicola Pecchioni
9. Anne C. Roulin

• Curated by eLife

  Summary: This paper has several strengths. It addresses Brachypodium distachyon population genetics and demography to help understand phenomena that have been investigated in less data-rich papers before. The authors do so with whole-genome sequencing of both a pre-existing global collection and additional "gap-filling" sampling. Analyses have been conducted using best practices, and most of the conclusions reflect the data and analyses presented.

  Major findings include the existence of large-scale population structure with three distinct lineages, discordance between geographical occurrence and genetic relatedness (clades within the lineages), and at shorter geographic scales, signs of dispersal without interbreeding. These patterns are explained by a combination of near-complete selfing and seed dispersal.

  The work attempts to cover a lot of ground, including selfing, seed dispersal, coalescence theory, microevolution, plasticity and frequency dependent selection, all mentioned in the abstract. The presentation would probably benefit from focusing on one or two aspects and making a stronger case for them.

  The reviewers noted that studies of this kind will often be descriptive due to the largely untestable nature of complex hypotheses of historical dispersal and evolution. Direct empirical testing of some of the hypotheses put forward here would require substantial experimental work (e.g. measuring the fitness of artificial hybrids to demonstrate post-zygotic reproductive isolation). As a first pass, simulations would likely suffice to test whether processes such as drift, selfing, and founder effects are sufficient to explain the population structure, or whether more complex processes such as frequency-dependent selection or reproductive isolation need to be invoked.

Reviewed by eLife

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

1. Peter Jan Hooikaas
2. Hugo GJ Damstra
3. Oane J Gros
4. Wilhelmina E van Riel
5. Maud Martin
6. Yesper TH Smits
7. Jorg van Loosdregt
8. Lukas C Kapitein
9. Florian Berger
10. Anna Akhmanova

• Curated by eLife

  Summary: This is a very interesting study addressing the question of microtubule cytoskeleton reorganization in the immunological synapse. Specifically, the work demonstrates the contribution of KIF21B for the control of the T cell microtubule (MT) network required for T cell polarization during immunological synapse formation. The authors use a variety of microscopy techniques, including expansion microscopy, controlled perturbations of the cell, and computer simulations to generate their results. The authors show that knockout of KIF21B results in longer MTs that result in an inability to polarise the MT network by a mechanism consistent with dynein motor function at the immunological synapse to capture long MTs and center the MT aster at the synapse. They use the Jurkat cell line, which is a classical model for this step in immune synapse function and fully appropriate. They show that KIF21B-GFP can rescue the knockout phenotype and then use this as a way to follow KIF12B dynamics in the Jurkat cells. KIF21B works by inducing pausing and catastrophe, thus, more MTs are shorter when present. They also rescue the defect in the KIF21B KOs with 0.5 nM vinblastine, that directly increases catastrophes, shortens the MTs and restores MT network polarization to the synapse. As a functional surrogate they investigate lysosome positioning at the synapse, which is one of the proposed functions of this cytoskeletal polarization. The use of expansion microscopy in this system is relatively new and clearly very powerful. The modelling component adds to the story and supports the sliding model proposed by Poenie and colleagues in 2006, but cannot say that there is no component of end capture and shrinkage as proposed by Hammer and colleagues more recently. Experiments and modelling are performed to a high standard and the results advance the field.

Reviewed by eLife

Intensity coded octopaminergic modulation of aversive crawling behavior in Drosophila melanogaster larvae

1. Florian Bilz
2. Madeleine-Marie Gilles
3. Adriana Schatton
4. Hans-Joachim Pflüger
5. Marco Schubert

• Curated by eLife

  Summary: This manuscript addresses an interesting question of how octopaminergic neurons regulate locomotor rhythms. Despite the interesting topic, the reviewers raised technical and mechanistic concerns that need to be addressed.

Reviewed by eLife

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

1. Palur V Raghuvamsi
2. Nikhil K Tulsian
3. Firdaus Samsudin
4. Xinlei Qian
5. Kiren Purushotorman
6. Gu Yue
7. Mary M Kozma
8. Wong Y Hwa
9. Julien Lescar
10. Peter J Bond
11. Paul A MacAry
12. Ganesh S Anand

• Curated by eLife

  Summary: This is a timely and interesting exploration of the interaction between the Spike protein of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, and the ACE2 receptor using hydrogen deuterium exchange mass spectrometry and molecular dynamics simulations. The Spike protein consists of two sub-domains S1 and S2 with the S1 needing to be cleaved-off so the S2 can become the fusion protein responsible for getting the SARS-CoV-2 into the cell. Structures are available but they do not shed light on how the protease furin can access the cleavage site between S1 and S2 in order to begin the process of fusion. The results suggest that the Spike-ACE2 interaction induces extremely long-range allosteric effects on the Spike protein that could trigger proteolysis of the Spike protein. Specifically, when ACE2 binds to the Spike protein, a conformational change occurs near the S1/S2 cleavage site, exposing it and likely making it more susceptible to furin cleavage. The binding also dampens exchange in the stalk region of the Spike protein. The authors refer to these regions as "dynamic hotspots in the pre-fusion state". The results of this work have implications for the development of small molecule inhibitors.

  In general, the work is timely, and the results will be of interest to many in the field. The major conclusions of the work are generally supported by the results.

Reviewed by eLife, ScreenIT

Bundle-specific associations between white matter microstructure and Aβ and tau pathology at their connecting cortical endpoints in older adults at risk of Alzheimer’s disease

1. Alexa Pichet Binette
2. Guillaume Theaud
3. François Rheault
4. Maggie Roy
5. D. Louis Collins
6. John C.S. Breitner
7. Judes Poirier
8. Maxime Descoteaux
9. Sylvia Villeneuve
10. for the PREVENT-AD Research Group

• Curated by eLife

  Summary: As you will find below, all three reviewers provided very positive technical reviews - there was a strong consensus that this is a well-executed study. The reviewers highlighted the large cohort of participants, the innovative and versatile use of neuroimaging techniques, and in particular the water-corrected diffusion and tau-PET measures, and the careful analysis. While we acknowledge these methodological strengths, we found it difficult to agree on the validity of the interpretation of the findings, considering the unexpected directionality of the results. In addition, we felt that without additional proof-of-concept (e.g. longitudinal study), the current experimental design does not provide sufficient evidence for an early brain pathology marker. However, it was agreed that the study provides a clear advancement relative to other studies looking at the relationship between different imaging domains in AD. As such, the present findings should be particularly valuable for an audience interested in white-matter pathology in neurodegenerative diseases.

Reviewed by eLife

Asymmetric Functional Gradients in the Human Subcortex

1. Xavier Guell
2. Jeremy D Schmahmann
3. John DE Gabrieli
4. Satrajit S Ghosh
5. Maiya R Geddes

• Curated by eLife

  Summary: This study investigates asymmetry in functional gradients in human thalamus, striatum and cerebellum. The authors found that the thalamus and the pallidum of the lenticular nucleus have strongly asymmetric principal functional gradients across the two hemispheres. In the case of the caudate and cerebellum, their 2nd and 3rd gradients were asymmetric. In general, the reviewers and editors found the study to be intriguing, but ultimately, felt that the dichotomous model, while interesting, was too speculative with no direct evidence presented. Considering also the lack of results on the functional significance of the asymmetries, the editors and reviewers felt that the study is better suited for a more specialized audience.

Reviewed by eLife

Extreme suction attachment performance from specialised insects living in mountain streams (Diptera: Blephariceridae)

1. Victor Kang
2. Robin T White
3. Simon Chen
4. Walter Federle

Reviewed by eLife

Bayesian inference of kinetic schemes for ion channels by Kalman filtering

1. Jan L Münch
2. Fabian Paul
3. Ralf Schmauder
4. Klaus Benndorf

• Curated by eLife

  Summary: The manuscript is well written and overall clear, and the mathematical treatment is a rigorous tour-de-force. However, the reviewers raised a number of points that need further clarification, better discussion or amendment. These concerns are likely to be addressable largely by changes to the main text and software documentation along with some additional analyses. The study is very nice and ambitious, but clarity is a bit impaired by dealing with perhaps too many issues. The state inference and the bayesian model selection are very important but completely different issues. The authors should consider whether they may be better treated separately, or for a more specialized audience.

Reviewed by eLife

Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

1. Vincent Robert
2. Ludivine Therreau
3. Vivien Chevaleyre
4. Eude Lepicard
5. Cécile Viollet
6. Julie Cognet
7. Arthur JY Huang
8. Roman Boehringer
9. Denis Polygalov
10. Thomas J McHugh
11. Rebecca Ann Piskorowski

• Curated by eLife

  Summary: The study describes the properties of inputs from the supramammillary nucleus (SuM) to the CA2 area of the hippocampus. Novel information is presented by the influence of the SuM input on the local hippocampal network in the CA2 and what the effect of this input is on network activity in the CA1. The authors use complementary methods to address this question including patch-clamp recordings and optogenetics. Overall the reviewers found this study important, the experiments well-designed and the data of high quality. However, there are several key points raised by the reviewers to strengthen the data in order to fully support the authors' conclusions, and addressing these will require additional experimental work. The list below summarizes the list of required experiments reviewers agreed would be necessary for having full confidence in the authors' conclusions:

  1. The authors would need to show the effect of SuM stimulation on synaptically triggered APs and not only on Aps evoked with a current step.

  2. The change in the balance of EPCs and IPSCs in a train should be demonstrated in a single cell.

  3. The properties of monosynaptic/disynaptic events should be compared and the lack of direct GABAergic input from the SuM demonstrated. The authors should quantify the delay time to light-evoked IPSCs to address whether the SuM-CA2 inputs are forming monosynaptic or disynaptic GABAergic connections to pyramidal neurons, as it is possible SuM neurons co-release glutamate and GABA to CA2. Given the importance of the mono vs. disynaptic innervation of different types of cells, the authors should go beyond the TTX experiments (as TTX would block a disynaptic EPSC) and also use 4-AP to recover the TTX blocked current to unequivocally prove that they inputs are monosynaptic.

  4. The preferential role of PV+ cells should be shown with a more selective pharmacological approach.

  5. The authors should elaborate on how SuM stimulation influences theta/gamma rhythms in the CA1 area.

  This manuscript is under revision at eLife.

Reviewed by eLife

Expansin-controlled cell wall stiffness regulates root growth in Arabidopsis

1. Marketa Samalova
2. Kareem Elsayad
3. Alesia Melnikava
4. Alexis Peaucelle
5. Evelina Gahurova
6. Jaromir Gumulec
7. Ioannis Spyroglou
8. Elena V. Zemlyanskaya
9. Elena V. Ubogoeva
10. Jan Hejatko

• Curated by eLife

  Summary: The reviewers felt that this is important work because in vivo characterization of expansins has lagged far behind their in vitro characterization. However, both reviewers also made important points about additional controls and statistical comparisons that are required to fully interpret and appreciate the results that are presented here. It seems that the role of expansins in the plant cell wall may be complex and nuanced. However, it is clear from the author's discussion of their results that significant further experimentation is required to bring new insight to the function of expansins in mediating plant root growth.

Reviewed by eLife

Auditory detection is modulated by theta phase of silent lip movements

1. Emmanuel Biau
2. Danying Wang
3. Hyojin Park
4. Ole Jensen
5. Simon Hanslmayr

• Curated by eLife

  Summary: The reviewers agreed that the paradigm proposed in this work is elegant, and the question timely and important. However, as detailed below, they highlighted several concerns about analysis choices and the interpretation of the data. While some of these can be addressed, it was felt that a major drawback of the present manuscript is that the behaviour and EEG are obtained separately and any links are hence only circumstantial.

Reviewed by eLife

Detecting fine and elaborate movements with piezo sensors, from heartbeat to the temporal organization of behavior

1. Maria Isabel Carreño-Muñoz
2. Maria Carmen Medrano
3. Thomas Leinekugel
4. Maelys Bompart
5. Fabienne Martins
6. Enejda Subashi
7. Franck Aby
8. Andreas Frick
9. Marc Landry
10. Manuel Grana
11. Xavier Leinekugel

• Curated by eLife

  Summary: The need to easily measure spontaneous behaviors in a robust fashion in experimental animals is an important problem in behavioral neuroscience. Thus, while this study is timely, the reviewers found fundamental flaws that substantially dampen enthusiasm for this work. The collective major concerns are: 1) the advance provided by this system, relative to already existing and commercially available software based on similar principles, was not clear, 2) critical technical details describing this system are missing 3) the diverse biological applications were not explored with sufficient depth and many of the related claims had potential alternative explanations.

Reviewed by eLife

Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome

1. Xavier A. Harrison
2. Allan D. McDevitt
3. Jenny C. Dunn
4. Sarah Griffiths
5. Chiara Benvenuto
6. Richard Birtles
7. Jean P. Boubli
8. Kevin Bown
9. Calum Bridson
10. Darren Brooks
11. Samuel S. Browett
12. Ruth F. Carden
13. Julian Chantrey
14. Friederike Clever
15. Ilaria Coscia
16. Katie L. Edwards
17. Natalie Ferry
18. Ian Goodhead
19. Andrew Highlands
20. Jane Hopper
21. Joseph Jackson
22. Robert Jehle
23. Mariane da Cruz Kaizer
24. Tony King
25. Jessica M. D. Lea
26. Jessica L. Lenka
27. Alexandra McCubbin
28. Jack McKenzie
29. Bárbara Lins Caldas de Moraes
30. Denise B. O’Meara
31. Poppy Pescod
32. Richard F. Preziosi
33. Jennifer K. Rowntree
34. Susanne Shultz
35. Matthew J. Silk
36. Jennifer E. Stockdale
37. William O. C. Symondson
38. Mariana Villalba de la Pena
39. Susan L. Walker
40. Michael D. Wood
41. Rachael E. Antwis

Reviewed by eLife

Cardiolipin targets a dynamin-related protein to the nuclear membrane

1. Usha Pallabi Kar
2. Himani Dey
3. Abdur Rahaman

Reviewed by eLife, Review Commons

Integron activity accelerates the evolution of antibiotic resistance

1. Célia Souque
2. José Antonio Escudero
3. R Craig MacLean

• Curated by eLife

  Summary: In this manuscript, the authors test the long-standing "evolution-on-demand" hypothesis of integrons. Using a combination of genetic construction work, experimental evolution, and WGS the authors present a convincing body of work favoring the presented hypothesis. They introduce three antibiotic gene cassettes into an integron and use an "evolutionary ramp" approach with gentamicin and demonstrate that the gentamicin resistance cassette shuffles towards the start of the integron. This provides compelling evidence favoring the evolutionary effects of an active class 1 integrase.

  The paper is clear, well written and demonstrates neatly the benefits of integron shuffling. The authors should also be given credit for including experimental data from an integron containing a clinical plasmid including resistance cassettes to the last resort antibiotics carbapenems. This is largely missing in the field.

  Our overall assessment of the manuscript is positive. However, a number of questions have been raised regarding the mechanistic aspects and conclusions of the paper. We are therefore suggesting additional assays to measure phenotypic effects of evolved integrons, and possibly data analyses on the negative controls. If these are not possible to perform, the main conclusions could be slightly altered instead to focus more on the genomics. Finally, we provide some suggestions on making the discussion more balanced and in clarifying the role of chromosomal mutations in the integron-facilitated evolution.

Reviewed by eLife

In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

1. Juan Carlos Jado
2. Michelle Dow
3. Krypton Carolino
4. Adam Klie
5. Gregory J. Fonseca
6. Trey Ideker
7. Hannah Carter
8. Elizabeth A. Winzeler

• Curated by eLife

  Summary: The authors examined the genomic basis of resistance evolution in human chronic myelogenous leukemia (CML) near-haploid cell lines to 5 separate chemotherapeutic agents.

  Using either whole genome or whole exome analysis, they found numerous instances of single nucleotide polymorphisms and copy number variants, including amplifications and deletions, among lines. They then used subsequent knockdown or knockout experiments to confirm that these variants, in fact, lead to increased resistance in these lines.

  The work is interesting, timely, and has potential clinical implications. For example, the resistance alleles identified here could be closely examined in future studies in order to develop treatment strategies. However, the experimental design has certain limitations, advances in understanding chemotherapy resistance mechanisms is currently modest, and the presentation of results can be improved. We feel overall that these could be addressed, but that they will require significant extra experimental work.

Reviewed by eLife

All-trans retinoic acid induces synaptic plasticity in human cortical neurons

1. Maximilian Lenz
2. Pia Kruse
3. Amelie Eichler
4. Jakob Straehle
5. Jürgen Beck
6. Thomas Deller
7. Andreas Vlachos

• Curated by eLife

  Summary: All three reviewers are highly enthusiastic about the study reporting the acute effects of retinoic acid on excitatory synaptic transmission and its underlying mechanisms. The experiments are well executed and the results convincing. Aside from some minor comments that require minimal additional experiments or further clarification, the reviewers expressed one major concern regarding the dentate gyrus LTP data. Although further experiments are required to clarify the concerns, the reviewers recommended removing the LTP figure from the present study as it is not well connected with the rest of the study.

Reviewed by eLife

Analysis of ultrasonic vocalizations from mice using computer vision and machine learning

1. Antonio HO Fonseca
2. Gustavo M Santana
3. Gabriela M Bosque Ortiz
4. Sérgio Bampi
5. Marcelo O Dietrich

Reviewed by eLife