eLife

Latest preprint reviews

1. Neural dynamics of semantic categorization in semantic variant of primary progressive aphasia

   This article has 13 authors:

   1. V Borghesani
   2. CL Dale
   3. S Lukic
   4. LBN Hinkley
   5. M Lauricella
   6. W Shwe
   7. D Mizuiri
   8. S Honma
   9. Z Miller
   10. B Miller
   11. JF Houde
   12. ML Gorno-Tempini
   13. SS Nagarajan

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: Borghesani and colleagues aimed to understand how dysfunction in the anterior temporal lobe (ATL) alters dynamic activity during semantic categorization. They contrast MEG responses between 18 patients with semantic variant Primary Progressive Aphasia (PPA) and 18 age-matched healthy controls. Both groups show similar profiles of behavioural performance on the task, and broad similarities in MEG responses. Critically, however, svPPA patients show enhanced gamma synchronization in the occipital lobe compared to controls. The authors interpret this as reflecting increased engagement of / reliance on early perceptual mechanisms for completing the task, as opposed to semantic identification of the picture.

     Overall, the reviewers found the manuscript interesting. As svPPA is a rare (but scientifically informative) disorder, the sample size is impressive, and given that relatively few MEG studies exist in PPA at all, this is an interesting dataset. However, the general opinion is that the results could be more fully characterized, which would allow for more expansive interpretations and inferences.

     This manuscript is in revision at eLife.

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

   Reviewed by eLife

2. Effects of order on memory of event times

   This article has 3 authors:

   1. Michelangelo Naim
   2. Mikhail Katkov
   3. Misha Tsodyks

   Reviewed by eLife

3. High-resolution mapping of the neutralizing and binding specificities of polyclonal rabbit serum elicited by HIV Env trimer immunization

   This article has 11 authors:

   1. Adam S. Dingens
   2. Payal Pratap
   3. Keara Malone
   4. Sarah K. Hilton
   5. Thomas Ketas
   6. Christopher A. Cottrell
   7. Julie Overbaugh
   8. John P. Moore
   9. P.J. Klasse
   10. Andrew B. Ward
   11. Jesse D. Bloom

   Reviewed by eLife

4. Recapitulating the frataxin activation mechanism in an engineered bacterial cysteine desulfurase supports the architectural switch model

   This article has 7 authors:

   1. Shachin Patra
   2. Cheng-Wei Lin
   3. Manas K. Ghosh
   4. Steven M. Havens
   5. Seth A. Cory
   6. David H. Russell
   7. David P. Barondeau

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: This study provides support for a proposed allosteric regulatory mechanism in a human iron-sulfur cluster biosynthesis protein that is linked to the human genetic disorder, Friedrich's Ataxia. In an approach guided by inspection of a structure of the human enzyme, the authors successfully converted a bacterial homolog lacking allosteric regulation into a system that behaves similarly to the human one. The work provides validation of the roles of accessory proteins in activating iron-sulfur cluster biosynthesis machinery. It also could open novel routes for therapeutic intervention in genetic disorders of this process in humans.

     The major concerns about the study center on the significance of the form of the human enzyme structure used as the basis for designing the mutagenesis/activity experiments in the bacterial enzyme. To bolster the underlying framework for the experiment design, the description of the existing human enzyme structures and how exactly they were used to select sites for mutagenesis in the bacterial counterparts should be improved to include more detail and balanced perspective. Experiments are suggested to show that activity enhancement upon addition of accessory proteins is specific to those factors, along with a more comprehensive discussion of the errors and reproducibility in activity measurements. Finally, the significance of the work would be elevated if the authors could use a similar approach to install activating mutations in the human enzyme - particularly if these could overcome the requirement for frataxin.

   Reviewed by eLife

5. The neural basis of intelligence in fine-grained cortical topographies

   This article has 3 authors:

   1. Ma Feilong
   2. J Swaroop Guntupalli
   3. James V Haxby

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: In this work, Feilong and colleagues use the Human Connectome Project fMRI data to investigate the degree to which the strength of functional connectivity is predictive of general intelligence, and the degree to which that predictive power is improved using the hyperalignment procedures their lab has developed. More specifically, the authors predict general intelligence using either coarse-grained functional connectivity (based on 360 ROIs) or fine-grained functional connectivity (vertex-wise) after hyperalignment. The results show a two-fold increase in variance explained in general intelligence between coarse-grained and fine-grained connectivity. This is a very clearly-written paper that presents an important result, which has the potential of great impact on the field of behavioral prediction. However, the reviewers and editors do have some significant concerns with the predictive modeling presented in this work.

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

   Reviewed by eLife

6. Long-term stability of cortical ensembles

   This article has 3 authors:

   1. Jesús Pérez-Ortega
   2. Tzitzitlini Alejandre-García
   3. Rafael Yuste

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: This work examines whether coincident firing of neurons in the visual cortex is preserved over a long timescale (one month) which is important because it provides insight into the stability and plasticity of neural circuits and visual representations. The authors find that subsets of identified neurons maintain coordinated firing despite some degree of flux in the firing activity across the population.

     All reviewers agreed that the question is important but found the analysis lacked depth and there were some technical issues in the experiments that should be addressed with a fuller discussion and potentially additional analysis to eliminate confounds/artefacts. In general, and in light of earlier work (some of which is not cited) the conclusions need to be more circumspect. Specifically:

     • There were concerns about movement/loss of cells/calcium indicator artefacts over this long imaging period that should be accounted for more rigorously.
     • The analysis applies a somewhat arbitrary criterion for stability (50% of cells remain responsive in an assembly). This threshold should be systematically explored and justified more carefully.
     • The wider literature on this topic should be more thoroughly cited, limitations of the study should be transparently laid out, claims about the overall stability found in this population response and its relevance to memories and behaviour should be moderated in line with the comments below.

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

   Reviewed by eLife

7. High-quality carnivoran genomes from roadkill samples enable comparative species delineation in aardwolf and bat-eared fox

   This article has 8 authors:

   1. Rémi Allio
   2. Marie-Ka Tilak
   3. Celine Scornavacca
   4. Nico L Avenant
   5. Andrew C Kitchener
   6. Erwan Corre
   7. Benoit Nabholz
   8. Frédéric Delsuc

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: Collectively, we liked a lot about your paper and we would accordingly like to encourage its continued evolution. However, we felt that the approximately equal balance at present between the roadkill genomics assembly pipeline and the phylogenetic and genetic diversity results was not justified, and we requested a shift accordingly as described below. Second, we require several analytical updates to the manuscript to ensure robustness of the main genetic diversity results.

   Reviewed by eLife

8. 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

9. 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

10. 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