eLife

Latest preprint reviews

1. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair

   This article has 8 authors:

   1. Judit Jimenez-Sainz
   2. Joshua Mathew
   3. Gemma Moore
   4. Sudipta Lahiri
   5. Jennifer Garbarino
   6. Joseph P Eder
   7. Eli Rothenberg
   8. Ryan B Jensen

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study provides a thorough functional analysis of three mutations in the BRCA2 gene that do not seem to necessarily cause breast cancer. The authors use functional assays in cancer cells and with recombinant proteins to determine that two BRCA2 variants, S1221P and T1980I, are indeed pathogenic, while the T13461 variant is fully functional and benign. The strength of the study is the rigorous assessment of these mutations in a variety of established assays for BRCA2. The work is likely to have a broad impact in the breast cancer 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 agreed to share their name with the authors.)

   Reviewed by eLife

2. An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice

   This article has 11 authors:

   1. Sudhuman Singh
   2. Torri D Wilson
   3. Spring Valdivia
   4. Barbara Benowitz
   5. Sarah Chaudhry
   6. Jun Ma
   7. Anisha P Adke
   8. Omar Soler-Cedeño
   9. Daniela Velasquez
   10. Mario A Penzo
   11. Yarimar Carrasquillo

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript from Singh and colleagues investigates neural connections between the central amygdala and the zona incerta, two subcortical brain regions previously implicated in pain, and further describes the role of the zona incerta to preclinical pain-related behavior in mice. This study employed anatomical tracing, electrophysiology, optogenetics, chemogenetics, and behavioral assays in various pain modalities to link the zona incerta to pain modulation by providing new evidence for a direct inhibitory connection from the central amygdala to the zona incerta that could explain neuropathic pain hypersensitivity. While rigorous, well written, and well executed, the study in its current form lacked evidence to directly support the PKCδ neurons in the central amygdala projecting to the zona incerta as being explicitly involved in this process.

     (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

3. Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation

   This article has 7 authors:

   1. Courtney J Smith
   2. Nasa Sinnott-Armstrong
   3. Anna Cichońska
   4. Heli Julkunen
   5. Eric B Fauman
   6. Peter Würtz
   7. Jonathan K Pritchard

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The paper by Smith and colleagues provides a framework for understanding a seemingly paradoxical observation in human genetics: two phenotypes may be closely correlated to each other, and the patterns of genetic variation that influence both phenotypes may be widely shared at the genome-wide level, but there are often specific genetic variants that show discordant patterns. Though the observations in this paper are derived from analysis of metabolic phenotypes, this may have broader relevance to interpreting the results from disease-related genetic association studies, and shed light on the processes that connect different disease phenotypes.

     (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 names with the authors.)

   Reviewed by eLife

4. KLC4 shapes axon arbors during development and mediates adult behavior

   This article has 8 authors:

   1. Elizabeth M Haynes
   2. Korri H Burnett
   3. Jiaye He
   4. Marcel W Jean-Pierre
   5. Martin Jarzyna
   6. Kevin W Eliceiri
   7. Jan Huisken
   8. Mary C Halloran

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study will be interesting to a broad audience of neuroscientists, as it reveals for the first time that mutations in klc4, which are known to cause a form of early onset hereditary spastic paraplegia in human, affect specific aspects of neuronal development and nervous system functions. High resolution movies of developing sensory neurons in vivo and behavioral assays support the key findings that klc4 plays an essential role in the control of neuronal morphogenesis and behavior. The data presented in the manuscript are overall of a descriptive nature but provide a foundation for future mechanistic studies aimed at addressing the specific functions of KLC4.

     (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

5. Airway basal cells show regionally distinct potential to undergo metaplastic differentiation

   This article has 9 authors:

   1. Yizhuo Zhou
   2. Ying Yang
   3. Lihao Guo
   4. Jun Qian
   5. Jian Ge
   6. Debora Sinner
   7. Hongxu Ding
   8. Andrea Califano
   9. Wellington V Cardoso

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Whether airway basal cells exhibit extensive cell state heterogeneity and whether this is relevant for their function has been unclear. This study provides important evidence that such heterogeneity exists and may dictate airway basal cell function in a spatially restricted manner.

     (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

6. Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex

   This article has 37 authors:

   1. Mean-Hwan Kim
   2. Cristina Radaelli
   3. Elliot R Thomsen
   4. Deja Monet
   5. Thomas Chartrand
   6. Nikolas L Jorstad
   7. Joseph T Mahoney
   8. Michael J Taormina
   9. Brian Long
   10. Katherine Baker
   11. Trygve E Bakken
   12. Luke Campagnola
   13. Tamara Casper
   14. Michael Clark
   15. Nick Dee
   16. Florence D'Orazi
   17. Clare Gamlin
   18. Brian E Kalmbach
   19. Sara Kebede
   20. Brian R Lee
   21. Lindsay Ng
   22. Jessica Trinh
   23. Charles Cobbs
   24. Ryder P Gwinn
   25. C Dirk Keene
   26. Andrew L Ko
   27. Jeffrey G Ojemann
   28. Daniel L Silbergeld
   29. Staci A Sorensen
   30. Jim Berg
   31. Kimberly A Smith
   32. Philip R Nicovich
   33. Tim Jarsky
   34. Hongkui Zeng
   35. Jonathan T Ting
   36. Boaz P Levi
   37. Ed Lein

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors made paired recordings from synaptically-connected excitatory and inhibitory neurons in slices of human neocortex and used posthoc molecular methods to identify major classes of the recorded interneurons. The principal finding is that, as found previously in rodent cortex, short-term plasticity of the synaptic connections from excitatory to inhibitory neurons depends on the molecular identity of the inhibitory neurons. This is important, as it suggests that many rodent studies carried out over the past decades are physiologically relevant to humans.

     (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. The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size

   This article has 6 authors:

   1. Rupali Ugrankar-Banerjee
   2. Son Tran
   3. Jade Bowerman
   4. Anastasiia Kovalenko
   5. Blessy Paul
   6. W Mike Henne

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors explore how the actin network in the fat body impacts nutrient uptake in multiple ways. Overall, this is an interesting study that sheds light on adipocyte cytoskeletal dynamics and it's impact on nutrient trafficking and fat body storage. The work can be further strengthened by additional validation of tools and 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. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

8. PTPN22 R620W gene editing in T cells enhances low-avidity TCR responses

   This article has 6 authors:

   1. Warren Anderson
   2. Fariba Barahmand-pour-Whitman
   3. Peter S Linsley
   4. Karen Cerosaletti
   5. Jane H Buckner
   6. David J Rawlings

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     PTPN22 is a protein tyrosine phosphatase which negatively regulates antigen receptor signaling. It has been proposed that several genetic variants of PTPN22 might be loss of function (LOF) variants, leading to hyper-responsive T cell proliferative and effector responses. The authors investigate how the PTPN22 R620W variant, associated with multiple autoimmune diseases, might contribute to breech of peripheral T cell tolerance. This work greatly advances and clarifies ongoing confusion of whether PTPN22 SNP(620W) is a LOF mutant.

     (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

9. Transcription factors underlying photoreceptor diversity

   This article has 6 authors:

   1. Juan M Angueyra
   2. Vincent P Kunze
   3. Laura K Patak
   4. Hailey Kim
   5. Katie Kindt
   6. Wei Li

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript offers a valuable transcriptomic data set of known types of adult zebrafish photoreceptors (rod and cones). The study further identifies a large set of differentially expressed transcription factors, many of which still have an unidentified function in photoreceptors. Using CRISPR F0 screening, the study shows that the two tbx2 zebrafish paralogues are involved in photoreceptors specification beyond what is currently known. The study uses a solid methodology and the results will be valuable for researchers interested in photoreceptor biology. At present, however, the manuscript has a misleading title and focus: the analysis of adult photoreceptors can hardly offer a scenario of the transcription factors involved in the specification of photoreceptors.

     (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

10. Emergence of time persistence in a data-driven neural network model

    This article has 5 authors:

    1. Sebastien Wolf
    2. Guillaume Le Goc
    3. Georges Debrégeas
    4. Simona Cocco
    5. Rémi Monasson

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      The authors show that how high-dimensional neural signals can be reduced to low-dimensional models with variables that can be directly linked to behavior. The reduced model can account for long timescales of persistent activity that arise from transisions between metastable model states. The authors further show that the rate of these transitions is modulated by water temperature according to the classic Arrhenius law.

      (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