eLife

Latest preprint reviews

1. Learning of probabilistic punishment as a model of anxiety produces changes in action but not punisher encoding in the dmPFC and VTA

   This article has 4 authors:

   1. David S Jacobs
   2. Madeleine C Allen
   3. Junchol Park
   4. Bita Moghaddam

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Punishment is key form of learning and behavior change, yet its core behavioral and brain mechanisms remain poorly understood and certainly less understood relative to reward learning. This manuscript uses dual fiber photometry to make an important advance in understanding how punishment is learned by studying how punishment changes action and punisher coding in the medial prefrontal cortex and ventral tegmental area of rats. The authors interpret the results as supporting a role for both areas in foraging in the face of risky outcomes. This work follows nicely on prior work and presents a straightforward and interesting experiment, using a validated anxiolytic to test what components of the neural response are related to this emotional component.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

2. Feedback inhibition underlies new computational functions of cerebellar interneurons

   This article has 5 authors:

   1. Hunter E Halverson
   2. Jinsook Kim
   3. Andrei Khilkevich
   4. Michael D Mauk
   5. George J Augustine

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this manuscript, the authors describe an inhibitory pathway from Purkinje cells in the cerebellum to a subset of molecular layer interneurons. The authors use in-vivo recordings to characterize these synaptic connections and probe their function during a delay conditioning task in vivo and using computer simulations. This is informative and an advance, but some claims regarding the function of this pathway need stronger substantiation. This is relevant to experimentalists and modelers interested in the cerebellum.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

3. Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn

   This article has 8 authors:

   1. Robert Philip Ganley
   2. Marilia Magalhaes de Sousa
   3. Kira Werder
   4. Tugce Öztürk
   5. Raquel Mendes
   6. Matteo Ranucci
   7. Hendrik Wildner
   8. Hanns Ulrich Zeilhofer

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper seeks to expand our understanding of how spinally-projecting serotonergic neurons either inhibit or facilitate nociception depending on physiological context. Capitalizing on differential susceptibility to AAVretro transduction, the authors suggest identification of functional serotonergic subunits within the medullary raphe - one that includes innervation of the superficial dorsal horn and may modulate sensitivity to peripheral thermal stimuli, and another that includes innervation of a deeper lamina of the dorsal horn and may modulate sensitivity to mechanical von Frey stimulation. As well, the viral techniques and findings may inform the design and interpretation of work in the field.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

4. Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway

   This article has 17 authors:

   1. Tolulope Sokoya
   2. Jan Parolek
   3. Mads Møller Foged
   4. Dmytro I Danylchuk
   5. Manuel Bozan
   6. Bingshati Sarkar
   7. Angelika Hilderink
   8. Michael Philippi
   9. Lorenzo D Botto
   10. Paulien A Terhal
   11. Outi Mäkitie
   12. Jacob Piehler
   13. Yeongho Kim
   14. Christopher G Burd
   15. Andrey S Klymchenko
   16. Kenji Maeda
   17. Joost CM Holthuis

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Sphingomyelin synthase 2 (SMS2) is a Golgi-localized enzyme that synthesizes sphingomyelin, a critical lipid in the plasma membrane, and mutations in SMS2 underly a rare genetic disorder of bone formation. This study shows that the disease mutations cause retention of SMS2 in the ER, which leads to sphingomyelin being produced in the wrong place and thus to a disrupted sphingomyelin and cholesterol gradient in the membranes of the secretory pathway. Additional experiments would improve the impact of this study in explaining the underlying reasons for some bone development disorders and providing cell biologists with new tools to manipulate lipids in cells.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

5. Targeting A-kinase anchoring protein 12 phosphorylation in hepatic stellate cells regulates liver injury and fibrosis in mouse models

   This article has 7 authors:

   1. Komal Ramani
   2. Nirmala Mavila
   3. Aushinie Abeynayake
   4. Maria Lauda Tomasi
   5. Jiaohong Wang
   6. Michitaka Matsuda
   7. Eki Seki

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The work is relevant to colleagues who study non-alcoholic fatty liver disease, the most common chronic disease in the world. It starts with steatosis (fat deposition) in the liver and progresses to very devastating stages of liver fibrosis. This study provides novel insight into mechanisms that result in liver inflammation and fibrosis and identifies a novel disease pathway, which is an attractive target for the treatment of liver fibrosis. The study can be improved, especially by refining the quality of microscopic images and techniques of protein chemistry.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

   Reviewed by eLife

6. Neural defensive circuits underlie helping under threat in humans

   This article has 2 authors:

   1. Joana B Vieira
   2. Andreas Olsson

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary

     This work aims to fill an important theoretical gap regarding the role of potential threats to the self in altruistic/prosocial helping. Much of the prevailing knowledge about the motivations for prosocial behavior focuses on the distress of the conspecific-in-need. Leveraging animal research, the authors hypothesize that defensive neural circuitry may aid prosocial helping under threat. Further building on prior work detailing responses along the threat imminence continuum, the authors hypothesize that cognitive fear circuits would respond to more distal threats whereas reactive fear circuits would respond to imminent threats. In addition to examining helping behavior under conditions of threat to self, the authors included representational similarity analyses (RSA) to examine how overlapping representations of self and other distress related to helping behavior. The potential to challenge existing empathy accounts of prosocial helping is intriguing and worthy of interrogation.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

   Reviewed by eLife

7. Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics

   This article has 34 authors:

   1. Irving Cancino-Muñoz
   2. Mariana G López
   3. Manuela Torres-Puente
   4. Luis M Villamayor
   5. Rafael Borrás
   6. María Borrás-Máñez
   7. Montserrat Bosque
   8. Juan J Camarena
   9. Caroline Colijn
   10. Ester Colomer-Roig
   11. Javier Colomina
   12. Isabel Escribano
   13. Oscar Esparcia-Rodríguez
   14. Francisco García-García
   15. Ana Gil-Brusola
   16. Concepción Gimeno
   17. Adelina Gimeno-Gascón
   18. Bárbara Gomila-Sard
   19. Damiana Gónzales-Granda
   20. Nieves Gonzalo-Jiménez
   21. María Remedios Guna-Serrano
   22. José Luis López-Hontangas
   23. Coral Martín-González
   24. Rosario Moreno-Muñoz
   25. David Navarro
   26. María Navarro
   27. Nieves Orta
   28. Elvira Pérez
   29. Josep Prat
   30. Juan Carlos Rodríguez
   31. Ma Montserrat Ruiz-García
   32. Hermelinda Vanaclocha
   33. Valencia Region Tuberculosis Working Group
   34. Iñaki Comas

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This work presents in-depth epidemiologic and phylogenetic analyses of tuberculosis cases across Valencia, Spain and comparator low-burden (Oxfordshire, UK) and high-burden (Karonga, Malawi) regions. Findings reveal that the "low burden" observed in Valencia is not in fact reflective of low transmission in this setting, with detected lineages likely to have circulated locally over the course of decades and to have been transmitted in the community.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

8. CFAP61 is required for sperm flagellum formation and male fertility in human and mouse

   This article has 14 authors:

   1. Siyu Liu
   2. Jintao Zhang
   3. Zine Eddine Kherraf
   4. Shuya Sun
   5. Xin Zhang
   6. Caroline Cazin
   7. Charles Coutton
   8. Raoudha Zouari
   9. Shuqin Zhao
   10. Fan Hu
   11. Selima Fourati Ben Mustapha
   12. Christophe Arnoult
   13. Pierre F Ray
   14. Mingxi Liu

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript describes a specific role for CFAP61 - a known component of axonemal radial spokes - in formation and function of sperm flagella in the mouse, and identifies CFAP61 as a disease gene linked to male infertility in a human patient. Furthermore, the authors show that CFAP61 interacts with several radial spoke components, including head and stalk regions, as well as with intraflagellar transport proteins. Overall, the quality of the data is high and the mouse work is consistent with a previously published report. The study underscores the physiological importance of CFAP61 in male fertility and will be of interest to cell and structural biologist studying flagella and motile cilia function, as well as to clinicians involved in fertility genetics. The study can serve a starting point to revealing the precise mechanism by which CFAP61 regulates sperm flagella formation and function and for further analysis human patient data.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

9. Individualized discovery of rare cancer drivers in global network context

   This article has 2 authors:

   1. Iurii Petrov
   2. Andrey Alexeyenko

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this work, Petrov and Alexeyenko present a novel network-based method, NEADriver, aimed at the identification of mutational (point mutations and copy number variants) driver genes across tumors. The authors evaluate ten large cancer cohorts and assess the overlap of their results with established cancer genes or datasets that are enriched for cancer genes. This manuscript addresses a topic of high interest in the cancer genomics community.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

10. Multistep loading of a DNA sliding clamp onto DNA by replication factor C

    This article has 6 authors:

    1. Marina Schrecker
    2. Juan C Castaneda
    3. Sujan Devbhandari
    4. Charanya Kumar
    5. Dirk Remus
    6. Richard K Hite

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This study is of relevance to the field of DNA replication, describing how an ATPase known as a 'clamp loader' opens a ring-shaped clamp protein and binds DNA to promote the deposition of the clamp around a nucleic acid duplex to support chromosomal replication. The findings on how different regions of the clamp loader bind to and open a clamp, and how the enzyme engages single-stranded and double-stranded regions of target DNAs provide new insights that further our understanding of the clamp loading reaction. It is intriguing that the clamp loader melts the end of the DNA duplex, an activity that had not been observed before or predicted.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife