eLife

Latest preprint reviews

1. Disparate bone anabolic cues activate bone formation by regulating the rapid lysosomal degradation of sclerostin protein

   This article has 12 authors:

   1. Nicole R Gould
   2. Katrina M Williams
   3. Humberto C Joca
   4. Olivia M Torre
   5. James S Lyons
   6. Jenna M Leser
   7. Manasa P Srikanth
   8. Marcus Hughes
   9. Ramzi J Khairallah
   10. Ricardo A Feldman
   11. Christopher W Ward
   12. Joseph P Stains

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: The article by Gould et al breaks new ground by demonstrating a role for lysosomal-mediated degradation in the mechanosensitive repression of Sclerostin levels in bone. Though the post-translational repression of Sclerostin has long been apparent, no one has yet unraveled the mechanisms. Therefore, this discovery is important to the skeletal biology community - both because of the findings themselves, and because the conditions/models used by this team to make these discoveries will be useful for other investigators, including their ability to manipulate and observe the rapid lysosome-dependent control of Sclerostin levels in vitro and in vivo in response to PTH or mechanical stimulation. In addition to the importance within this field, the work has broad impact on multiple levels including a) the clinical relevance for understanding and potentially treating osteoporosis and the skeletal phenotypes in individuals with lysosomal disease, and b) the mechanoregulation of lysosomal function and its relationships to crinophagy, which has implications not only for the regulation of Sclerostin, but also for other factors in and beyond the skeleton (RANKL, insulin).

     Essential revisions:

     The study is elegantly designed, clearly communicated, and rigorously conducted. However, the reviewers require additional data to support the overall conclusion on the significance of lysosome-mediated degradation of sclerostin in skeletal biology. First, it is important to elaborate on what gives the authors confidence that the inhibitors were effective and act as expected throughout the study - but especially Bafilomycin A1 and Apocynin in vivo. If BafA1 and Apocynin treatment in vivo work as expected, they should prevent the rapid load-dependent repression of Sclerostin levels (shown in Figure 1D). Second, the author's demonstration of mechanical load-dependent changes in sclerostin localization in osteocytes lysosomes in vivo by immunohistochemistry would be important to support the in vivo relevance of this pathway in the acute regulation of sclerostin levels. While the western blotting of mechanically loaded mouse ulnas showing previously-undocumented acute reductions in lysate sclerostin levels is interesting, it is unclear if these changes are caused by mechanical loading-induced lysosomal function.

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

   Reviewed by eLife

2. Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

   This article has 6 authors:

   1. Jonathan R. Soucy
   2. Gabriel Burchett
   3. Ryan Brady
   4. David T. Breault
   5. Abigail N. Koppes
   6. Ryan A. Koppes

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: All three reviewers were not convinced that this screening platform has been properly validated vis-à-vis the neurobiology of the adrenal gland, nor that it has a physiologic relevance for the understanding of living processes and organs.

   Reviewed by eLife

3. Influence of sensory modality and control dynamics on human path integration

   This article has 5 authors:

   1. Akis Stavropoulos
   2. Kaushik J Lakshminarasimhan
   3. Jean Laurens
   4. Xaq Pitkow
   5. Dora E Angelaki

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: In this manuscript, the authors investigated the importance of visual and vestibular sensory cues and the underlying motion dynamics to the accuracy of spatial navigation by human subjects. A virtual environment coupled with a 6-degrees of motion platform, as described in prior studies, allowed precise control over sensory cues and motion dynamics. To investigate whether control dynamics influence performance, the transfer function between joystick deflection and self-motion velocity was modified at each trial, resulting in subjects relying more on velocity or acceleration to find their way. To explain the main result that navigation error depends on control dynamics, the authors propose a probabilistic model in which an internal estimate of dynamics is biased by a strong prior. Overall, the three reviewers agree that additional data are not necessary. However, the analyses need to be clarified and the conclusion better justified.

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

   Reviewed by eLife

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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