Evaluated articles

PIE-1 promotes SUMOylation and activation of HDAC1 during the C. elegans oogenesis

1. Heesun Kim
2. Yue-He Ding
3. Shan Lu
4. Mei-Qing Zuo
5. Darryl Conte
6. Meng-Qiu Dong
7. Craig C. Mello

• Curated by eLife

  Summary: In this paper you describe experiments showing that PIE-1 is sumoylated at K68, and that K68 sumoylation plays a role in PIE-1 interaction with HDA-1 and its sumoylation, which leads to its activation. The reviewers found the sumoylation dependence of PIE-1 function in piRNA silencing to be of interest, but raised major issues that need to be addressed. In particular, more mechanistic insights into how sumoylation of PIE-1 at K68 enhances HDA-1 sumoylation and regulation are required.

  This is a co-submission with the manuscript https://www.biorxiv.org/content/10.1101/2020.08.17.254466v2

Reviewed by eLife

Multiple neuronal networks coordinate Hydra mechanosensory behavior

1. Krishna N Badhiwala
2. Abby S Primack
3. Celina E Juliano
4. Jacob T Robinson

• Curated by eLife

  Summary: Specifically, all of the reviewers agreed that the emerging Hydra system holds great promise for neuroscience discoveries. Moreover, some of the findings presented here have the potential to be of use to other scientists who work in this system. However, we felt that the findings here were too preliminary and underdeveloped. In particular reviewers felt that 1) multiple locations across the Hydra's body should be stimulated coupled with mapping the behavioral and neuronal correlates of such stimulation, 2) the pan-neuronal nature of the bulk calcium measurements made it challenging to fully appreciate which neuronal circuits might be driving the sensorimotor responses, 3) uniform proxies for measuring/plotting the behavior would be useful, 4) the ablation studies lacked cellular resolution, similar to the calcium imaging experiments.

Reviewed by eLife

A novel, ataxic mouse model of ataxia telangiectasia caused by a clinically relevant nonsense mutation

1. Harvey Perez
2. May F Abdallah
3. Jose I Chavira
4. Angelina S Norris
5. Martin T Egeland
6. Karen L Vo
7. Callan L Buechsenschuetz
8. Valentina Sanghez
9. Jeannie L Kim
10. Molly Pind
11. Kotoka Nakamura
12. Geoffrey G Hicks
13. Richard A Gatti
14. Joaquin Madrenas
15. Michelina Iacovino
16. Peter J McKinnon
17. Paul J Mathews

Reviewed by eLife

Polygenic prediction of school performance in children with and without psychiatric disorders

1. Veera M. Rajagopal
2. Betina B Trabjerg
3. Jakob Grove
4. Henriette T. Horsdal
5. Liselotte Petersen
6. Cynthia M. Bulik
7. Jonas Bybjerg-Grauholm
8. Marie Bækvad-Hansen
9. David M Hougaard
10. Ole Mors
11. Merete Nordentoft
12. Thomas Werge
13. Preben Bo Mortensen
14. Esben Agerbo
15. Anders D. Borglum
16. Ditte Demontis

• Curated by eLife

  Summary: This is an interesting study researching how educational achievement (EA) can be predicted using genomic data when the sample is stratified to those without and those with diagnoses of common psychiatric disorders. The study is well powered using an impressive and representative sample and offers insights into the etiology of associations between psychiatric traits and educational achievement. The authors find evidence that the influence of common variants on EA is attenuated in individuals with a diagnosis of autism spectrum disorder (ASD) or ADHD.

Reviewed by eLife

Early maternal loss leads to short- but not long-term effects on diurnal cortisol slopes in wild chimpanzees

1. Cédric Girard-Buttoz
2. Patrick J Tkaczynski
3. Liran Samuni
4. Pawel Fedurek
5. Cristina Gomes
6. Therese Löhrich
7. Virgile Manin
8. Anna Preis
9. Prince F Valé
10. Tobias Deschner
11. Roman M Wittig
12. Catherine Crockford

• Curated by eLife

  Summary: This paper tests the biological embedding model by asking whether and how early maternal loss affects cortisol levels and diurnal cortisol slopes among wild chimpanzees at the Tai Forest, Côte d'Ivoire. The results suggest that maternal loss alters the HPA stress axis in wild chimpanzees, but these effects are not visible later in life. Authors suggest that the lack of a later life association between maternal loss and cortisol levels may be due to selective early mortality of individuals with high cortisol levels but did not provide any survival or behavioural data to show that orphans and non-orphans differ in any fitness-related traits other than cortisol. Furthermore, the association between cortisol and the HPA axis is in the opposite direction to that observed in humans and there seems to be no significant increase in cortisol in orphans compared to non-orphans. Overall, the study is the result of extensive fieldwork, the number of samples collected is impressive and the subject is very interesting.

  The analyses will benefit greatly if the authors use effect sizes and confidence intervals for inferences instead of p-values. This may solve the significance threshold issues. Moreover, the reliance on p-values seem to limit the value of the data. For example, authors suggest that results from model 1 should be treated with caution because the full model is not significantly different from the null model, but by relying on it as the key finding of the study without exploring effect sizes, it does not seem that they did exercise sufficient caution.

Reviewed by eLife

Increased influence of prior choices on perceptual decisions in autism

1. Helen Feigin
2. Shir Shalom-Sperber
3. Ditza A Zachor
4. Adam Zaidel

• Curated by eLife

  Summary: The study addresses a timely and important question of the role of prior choices on perceptual decisions in individuals diagnosed with autism; 17 high functioning (but not mild cases) children and teenagers (8-17 years) with ASD. The experiments are well motivated and thoughtfully designed. Using a model to dissociate the contribution of prior stimuli and choices, the authors found a strong effect of prior choices not stimuli, which is stronger in ASD than controls. Similar results from another data set are also reported.

  Overall, this is a strong study with a sophisticated protocol, elaborate data analysis, ASD participants who were tested on a large battery, in-depth analysis of the literature with interesting insights, interesting results and a well written manuscript.

  The first two experiments provided compelling evidence that prior choices affect perceptual decision making in ASD, but the outcome of the response invariant condition suggests that the authors' interpretation goes beyond the data. This has serious implications for the interpretations of the findings. Also, the bias interpretation should be informed by measures of performance.

Reviewed by eLife

Intravital deep-tumor single-beam 3-photon, 4-photon, and harmonic microscopy

1. Gert-Jan Bakker
2. Sarah Weischer
3. Júlia Ferrer Ortas
4. Judith Heidelin
5. Volker Andresen
6. Marcus Beutler
7. Emmanuel Beaurepaire
8. Peter Friedl

• Curated by eLife

  Summary: Nonlinear microscopy is in the unique position that high-resolution images of cells and other tissue components can be obtained in live tissue. However, scattering and absorption limit the penetration depth. The impact of nonlinear microscopy in biomedicine and biology would be much improved if higher imaging depths can be achieved. In this manuscript, the authors show they can accomplish imaging in complex specimens using 3- and 4-photon excitation, deeper in the specimen than comparable optics can accomplish with 2-photon excitation laser scanning microscopy. Using a customised commercial system, the authors have incorporated a high-powered laser source with an OPA and dispersion compensation to generate either 1330nm or 1650nm laser lines with high peak pulse energies at low pulse repetition rates. They then compare the relative capabilities of each laser line in terms of number of fluorescence emission channels measured (skin tumour xenografts), fluorescence bleaching analysis and functional toxicity thresholds and fluorescence signal attenuation (excised murine bone).

  This is a very interesting study with some potentially important findings from a technical perspective. However, there is a disconnect at present between the quality of the work and the quality of the presentation. There are many areas of quantitative imaging and intravital imaging that are well known to those in the direct field, and that are a complete mystery to the vast majority of those that are not. It would therefore be highly beneficial to restructure the manuscript in such a way that the findings can reach the many researchers that could benefit from this powerful approach rather than the few who already use it.

Reviewed by eLife

Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis

1. Herdson Renney de Sousa
2. Getúlio Pereira de Oliveira
3. Stefânia de Oliveira Frazão
4. Kaio César de Melo Gorgonha
5. Camila Pereira Rosa
6. Emãnuella Melgaço Garcez
7. Joaquim Lucas
8. Amabel Fernandes Correia
9. Waleriano Ferreira de Freitas
10. Higor Matos Borges
11. Lucas Gomes de Brito Alves
12. Hugo Costa Paes
13. Luciana Trilles
14. Márcia dos Santos Lazera
15. Marcus de Melo Teixeira
16. Vitor Laerte Pinto
17. Maria Sueli Soares Felipe
18. Arturo Casadevall
19. Ildinete Silva-Pereira
20. Patrícia Albuquerque
21. André Moraes Nicola

• Curated by eLife

  Summary: The description of how faster melanization is associated with LC3-mediated phagocytosis evasion, virulence and outcomes in humans is interesting and does provide some new information. In general, the study has been executed well, with clear articulation of the results and appending conclusions. However, the work falls short of investigating any substantive mechanistic basis for the observations and how they relate to the broader metabolism in Cryptococcus. .

Reviewed by eLife

Inhibitory interneurons show early dysfunction in a SOD1 mouse model of amyotrophic lateral sclerosis

1. Clarissa F. Cavarsan
2. Preston R. Steele
3. Landon T. Genry
4. Emily J. Reedich
5. Lynn M. McCane
6. Kay J. LaPre
7. Alyssa C. Puritz
8. Marin Manuel
9. Natallia Katenka
10. Katharina A. Quinlan

• Curated by eLife

  Summary: In the present study, the authors searched for early signs (during the neonatal period) of amyotrophic lateral sclerosis (ALS) disease focusing on a specific class of spinal interneurons; i.e.: glycinergic interneurons. In SOD1 mice, they aimed at testing whether these inhibitory neurons exhibit measurable changes at young age that could then contribute to the MN pathology known to develop later. The originality of this study is that, for the first time, it examines specifically inhibitory neurons. The authors investigated the morphological and electrophysiological properties of lumbar glycinergic interneurons in the spinal ventral horn in one model of SOD1 mice compared to WT P6-P10 mice. In addition, the authors more specifically considered Renshaw cells in this process and found that these cells were less excitable in SOD1 mice.. Based on these experimental data they created a statistical model to make predictions on RC cells (and non-Renshaw cells found to be more excitable in SOD1 mice) to further demonstrate that early changes in their excitability could account for the disease.

  Despite the fact that this paper addresses the potential role of an unprecedentedly investigated class of neurons (inhibitory ones) in ALS disease, reviewers pointed to several concerns. First, there is a major problem with the identification of the Renshaw cells. Indeed arguments using the localization within the ventral horn of the spinal cord, the calbindin expression, the size and the number are questionable as it is done here. In addition, because the characteristics of this type of cell has been later used for the predictive statistical model, it importantly attenuates the validity of the model and credibility of the conclusions reached. Finally, because of the problems addressed above and because this paper is mainly descriptive without bringing real new hypotheses this paper might not participate in moving the field of ALS significantly forward. Thus, the three reviewers and I agree that the paper would be better suited for a specialised audience assuming detailed comments about the methodology are addressed.

Reviewed by eLife

Contributions of h- and Na+/K+ Pump Currents to the Generation of Episodic and Continuous Rhythmic Activities

1. Simon A. Sharples
2. Jessica Parker
3. Alex Vargas
4. Jonathan J. Milla-Cruz
5. Adam P. Lognon
6. Ning Cheng
7. Leanne Young
8. Anchita Shonak
9. Gennady S. Cymbalyuk
10. Patrick J. Whelan

• Curated by eLife

  Summary: Both reviewers found that the analysis of data was too shallow and that the HCO model was insufficiently justified in the context of spinal cord CPGs. The reviewers argue that a more robust analysis including a discussion of the dynamic properties of the model (in the context of dynamic switching) was needed to support conclusions.

Reviewed by eLife

A home and rescue gene drive efficiently spreads and persists in populations

1. Nikolay P. Kandul
2. Junru Liu
3. Jared B. Bennett
4. John M. Marshall
5. Omar S. Akbari

Reviewed by eLife

Retinal circuits driving a non-image forming visual behavior

1. Corinne Beier
2. Ulisse Bocchero
3. Zhijing Zhang
4. Nange Jin
5. Stephen C. Massey
6. Christophe P. Ribelayga
7. Kirill Martemyanov
8. Samer Hattar
9. Johan Pahlberg

• Curated by eLife

  Summary: The reviewers all appreciated the potential of the work and felt that the general approach followed was strong. The reviewers, however, raised several important concerns. Discussion among the reviewers emphasized the importance of these. Chief among these was a concern about the extent to which the paper breaks new ground in a way that will appeal to a broad audience. Specifically, several of the results reported are expected based on prior work on the retinal pathways involved, and the results that do not fit with existing knowledge were not pursued in sufficient detail. These, and several other concerns, are detailed in the individual reviews below.

Reviewed by eLife

Global gradients in intertidal species richness and functional groups

1. Jakob Thyrring
2. Lloyd S Peck

Reviewed by eLife

Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system

1. Christopher Icke
2. Freya J Hodges
3. Karthik Pullela
4. Samantha A McKeand
5. Jack Alfred Bryant
6. Adam F Cunningham
7. Jeff A Cole
8. Ian R Henderson

• Curated by eLife

  Summary: All three reviewers were enthusiastic about the identification and characterization of a hybrid secretion system involved in lipoprotein acylation and trafficking. We were impressed by the strength and extent of the data and the clever use of genetic, biochemical and bioinformatic approaches. At the same time, there was agreement that the conclusion that acylation is involved in CexE secretion is not fully supported. There was also consensus that overlap between this study and the 2020 PLOS Pathogen paper from Belmont-Monroy, necessitates more direct acknowledgement.

Reviewed by eLife

De Novo Lipid Labeling for Comprehensive Analysis of Subcellular Distribution and Trafficking in Live Cells

1. Jun Zhang
2. Jia Nie
3. Haoran Sun
4. John-Paul Andersen
5. Yuguang Shi

• Curated by eLife

  Summary: Zhang et al. describe an interesting method to label newly synthesized lipids with fluorescent fatty acids and track their movement in cells. All reviewers agreed that this could potentially be a useful tool. However, they all raised concerns regarding the rigor of the characterization of this methodology.

Reviewed by eLife

Does Self-Reassurance Reduce Neural and Self-Report Reactivity to Negative Life Events?

1. Jeffrey J. Kim
2. James R. Doty
3. Ross Cunnington
4. James N. Kirby

• Curated by eLife

  Summary: Kim and colleagues present a secondary analysis of an already published imaging dataset in 40 participants going through a two-week compassion training paradigm. They show participants standardized statements that are emotional or neutral and further have participants either engage in "self-criticism" or "self-reassurance" while considering the statements. The authors report on differences in brain regions (what they refer to as "neural pain") depending on criticism or reassurance condition. Concerns with the conceptual framework, approach, and interpretation substantially dampened our enthusiasm.

Reviewed by eLife

Ex vivo observation of granulocyte activity during thrombus formation

1. Daria S. Morozova
2. Alexey A. Martyanov
3. Sergei I. Obydennyi
4. Julia-Jessica D. Korobkin
5. Alexey V. Sokolov
6. Ekaterina V. Shamova
7. Irina V. Gorudko
8. Anna L. Khoreva
9. Anna Shcherbina
10. Mikhail A. Panteleev
11. Anastasia N. Sveshnikova

• Curated by eLife

  Summary: Specifically, the proposed model system is valuable to study ex vivo the infiltration of the growing thrombus by granulocytes using fluorescent microscopy. In addition, this system has the potential to facilitate investigations on the role of granulocytes in thrombus growth and immune-thrombosis. Granulocytes have been classified into two different types based on their DiOC6 staining pattern, namely, type A with uniform DiOC6 and type B with cluster-like DiOC6. However, it remains unclear if the staining pattern is homogeneously so clear-cut and if the type A and B granulocytes are in addition defined by their velocity. Granulocyte activation process by "priming agents" has to be validated and the rationale for using the chosen agents needs to be provided. Finally, better-defined controls for the part of the paper dedicated to the synergistic effect between granulocytes and platelets during thrombus growth are necessary. Because in the Wiskott-Aldrich syndrome (WAS) granulocyte motility as well as platelet number and function are impaired, blood from patients with WAS is not an appropriate control for this study. For example, for the control experiments, the following controls might be used in replacement of WAS blood: (1) blood from thrombocytopenic patients or platelet-depleted blood and (2) blood in which granulocyte mobility/activation is inhibited. Finally, it would be interesting to see if neutrophil extracellular traps (NETs) develop in this model system.

Reviewed by eLife

Gene expression has more power for predicting in vitro cancer cell vulnerabilities than genomics

1. Joshua M. Dempster
2. John M. Krill-Burger
3. James M. McFarland
4. Allison Warren
5. Jesse S. Boehm
6. Francisca Vazquez
7. William C. Hahn
8. Todd R. Golub
9. Aviad Tsherniak

• Curated by eLife

  Summary: The authors propose a new approach to the derivation of cancer signatures and compare the relative impact of gene expression data with respect to other variables, particularly SVN and CVNs. The simplicity of the idea and of the technical approach, to the point of singling out a single gene predictive value, is a positive aspect. There are also critical aspects that will require substantial revision including the underlying influence of tissue specific genes. Overall, the paper provides a good basis for the generation of specific hypotheses that can be followed by additional validation studies at the computational and/or experimental level.

Reviewed by eLife

Reinstatement of Cortical Outcome Representations during Higher-Order Learning

1. Lennart Luettgau
2. Emanuele Porcu
3. Claus Tempelmann
4. Gerhard Jocham

• Curated by eLife

  Summary: All reviewers agreed that the neural mechanisms by which value is conferred to stimuli that were never directly paired with reinforcement is an important topic. However, individual reviewers raised questions regarding the study design and data analysis. In particular, reviewers agreed it was not clear how you could distinguish BOLD responses to CS1 and CS2 given the temporal proximity of their presentation. They also wondered whether the current results would provide enough advance beyond previous work.

Reviewed by eLife

Asprosin Neutralizing Antibodies as a Treatment for Metabolic Syndrome

1. Ila Mishra
2. Clemens Duerrschmid
3. Zhiqiang Ku
4. Wei Xie
5. Elizabeth Sabath Silva
6. Jennifer Hoffmann
7. Wei Xin
8. Ningyan Zhang
9. Zhiqiang An
10. Atul R. Chopra

• Curated by eLife

  Summary: Mishra et al. present data characterizing the effect of asprosin neutralizing antibodies on the parameters of metabolic syndrome (weight, glucose, lipids, etc). This group were the initial discoverers and characterized asprosin as a hormone that increases blood sugar and stimulates appetite. In their Nature Medicine 2017 article they also present data on a neutralizing antibody. In this follow-up manuscript the group characterizes the impact of neutralizing monoclonal antibodies on metabolic parameters of three mouse models of obesity (DIO, NASH diet and Leptin receptor knockout). The translational focus of the manuscript is potential use of monoclonal antibodies against aprosin as a treatment of metabolic syndrome.

Reviewed by eLife