eLife

Latest preprint reviews

1. HDAC1 SUMOylation promotes Argonaute-directed transcriptional silencing in C. elegans

   This article has 7 authors:

   1. Heesun Kim
   2. Yue-He Ding
   3. Gangming Zhang
   4. Yong-Hong Yan
   5. Darryl Conte
   6. Meng-Qiu Dong
   7. Craig C Mello

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: In this paper, your studies showed that sumoylation of HDA-1, a type 1 HDAC, at two C-terminal Lys residues plays a role in establishing transcriptional silencing of piRNA-regulated genes in C. elegans through enhanced NuRD complex interaction and histone H3 deacetylation. The reviewers all found the link between HDA-1 sumoylation and silencing to be interesting, but raised a number of issues that need to be addressed.

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

   Reviewed by eLife

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

   This article has 7 authors:

   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

   This article has been curated by 1 group:

   • 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

3. Multiple neuronal networks coordinate Hydra mechanosensory behavior

   This article has 4 authors:

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

   This article has been curated by 1 group:

   • 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

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

   This article has 17 authors:

   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

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

   This article has 16 authors:

   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

   This article has been curated by 1 group:

   • 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

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

   This article has 12 authors:

   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

   This article has been curated by 1 group:

   • 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

7. Increased influence of prior choices on perceptual decisions in autism

   This article has 4 authors:

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

   This article has been curated by 1 group:

   • 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

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

   This article has 8 authors:

   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

   This article has been curated by 1 group:

   • 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

9. Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis

   This article has 21 authors:

   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

   This article has been curated by 1 group:

   • 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

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

    This article has 10 authors:

    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

    This article has been curated by 1 group:

    • 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