eLife

Latest preprint reviews

1. Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies

   This article has 19 authors:

   1. Richard F Oppong
   2. Antonio Terracciano
   3. Martin Picard
   4. Yong Qian
   5. Thomas J Butler
   6. Toshiko Tanaka
   7. Ann Zenobia Moore
   8. Eleanor M Simonsick
   9. Krista Opsahl-Ong
   10. Christopher Coletta
   11. Angelina R Sutin
   12. Myriam Gorospe
   13. Susan M Resnick
   14. Francesco Cucca
   15. Sonja W Scholz
   16. Bryan J Traynor
   17. David Schlessinger
   18. Luigi Ferrucci
   19. Jun Ding

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper makes a comprehensive survey of the relationship between mtDNAcn and the personality dimensions, as well as how and whether they mediate the relationships between personality dimensions and mortability as well as other behavioural measures that may lead to mortality. More work needs to be performed to truly understand the relationship between personality dimensions and mortality, as well as the physiological traits (like mtDNAcn) that may be mediating it.

     (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. Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer

   This article has 9 authors:

   1. Zaoqu Liu
   2. Siyuan Weng
   3. Qin Dang
   4. Hui Xu
   5. Yuqing Ren
   6. Chunguang Guo
   7. Zhe Xing
   8. Zhenqiang Sun
   9. Xinwei Han

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Liu et al. describes an unsupervised method that clusters colorectal cancer samples based on perturbations to gene interactions. They show that this method strongly suggests 6 distinct clusters of samples and identifies phenotypes associated with the clusters, including survival, drug response, immune phenotype, response to immune checkpoint inhibitors and perturbed pathways. This is an interesting and significant manuscript, which has been well conducted.

     (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

3. Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling

   This article has 26 authors:

   1. Mengyang Fan
   2. Wenchao Lu
   3. Jianwei Che
   4. Nicholas P Kwiatkowski
   5. Yang Gao
   6. Hyuk-Soo Seo
   7. Scott B Ficarro
   8. Prafulla C Gokhale
   9. Yao Liu
   10. Ezekiel A Geffken
   11. Jimit Lakhani
   12. Kijun Song
   13. Miljan Kuljanin
   14. Wenzhi Ji
   15. Jie Jiang
   16. Zhixiang He
   17. Jason Tse
   18. Andrew S Boghossian
   19. Matthew G Rees
   20. Melissa M Ronan
   21. Jennifer A Roth
   22. Joseph D Mancias
   23. Jarrod A Marto
   24. Sirano Dhe-Paganon
   25. Tinghu Zhang
   26. Nathanael S Gray

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Fan and colleagues disclose the development of covalent TEAD inhibitors and they report on the therapeutic potential of this class of agents in the treatment of TEAD-YAP-driven cancers (e.g., malignant pleural mesothelioma, MPM). Optimized derivatives of a previously reported covalent TEAD inhibitor are described and characterized, using diverse profiling approaches that range from biochemical and cell-based assays to X-ray co-crystallographic analysis and in vivo efficacy in a relevant mouse xenograft model. The manuscript represents an impressive and deep characterization of this small molecule class. The authors' claims and conclusions are very well supported and justified by the data, although differentiation from a very closely related compound termed K-975 is not entirely clear as currently presented.

     (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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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