eLife

Latest preprint reviews

1. Generative power of a protein language model trained on multiple sequence alignments

   This article has 3 authors:

   1. Damiano Sgarbossa
   2. Umberto Lupo
   3. Anne-Florence Bitbol

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This valuable paper proposes an innovative iterative masking approach that enables models such as the MSA Transformer to generate new protein sequence designs, which are validated using a wide-ranging set of computational experiments. A key strength of the MSA Transformer is the ability to learn and generalize across protein families, enabling impressive performance across a range of downstream tasks. However, to date, these models have not been used to generate new protein sequence designs. The approach proposed in this paper is quite novel, and a number of metrics are used to examine the resulting performance of the MSA Transformer at generating new protein sequences from specific families.

     (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

2. Early myelination involves the dynamic and repetitive ensheathment of axons which resolves through a low and consistent stabilization rate

   This article has 2 authors:

   1. Adam R Almeida
   2. Wendy B Macklin

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Almeida and Macklin provide one of the first studies to closely examine early oligodendrocyte behaviors at high resolution. These studies use live imaging in zebrafish to provide valuable new insights about the earliest onset of myelination in the central nervous system and add to a body of work showing how oligodendrocytes initiate and maintain myelin sheaths.

     (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

3. Two novel, tightly linked, and rapidly evolving genes underlie Aedes aegypti mosquito reproductive resilience during drought

   This article has 11 authors:

   1. Krithika Venkataraman
   2. Nadav Shai
   3. Priyanka Lakhiani
   4. Sarah Zylka
   5. Jieqing Zhao
   6. Margaret Herre
   7. Joshua Zeng
   8. Lauren A Neal
   9. Henrik Molina
   10. Li Zhao
   11. Leslie B Vosshall

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this manuscript, of interest to those studying insect reproductive biology and specifically mosquitoes, the authors show that females of the yellow fever mosquito retain eggs when fresh water is not readily available. The authors then use RNA expression analyses to identify genes potentially involved in the trait. This leads the authors to focus on two genes that seem to be recent duplicates. The authors generate genetic knockouts and use these to show that these two alleles affect the trait in question. The study includes interesting and technically impressive experiments, but the framing in the context of previous work could be improved.

     (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

4. Effector target-guided engineering of an integrated domain expands the disease resistance profile of a rice NLR immune receptor

   This article has 12 authors:

   1. Josephine HR Maidment
   2. Motoki Shimizu
   3. Adam R Bentham
   4. Sham Vera
   5. Marina Franceschetti
   6. Apinya Longya
   7. Clare EM Stevenson
   8. Juan Carlos De la Concepcion
   9. Aleksandra Białas
   10. Sophien Kamoun
   11. Ryohei Terauchi
   12. Mark J Banfield

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Engineering NLR proteins to improve disease resistance in crop plants is a major goal of the field. This study applies knowledge from structural and evolutionary studies of the rice NLR protein Pik-1 and cognate effector protein AVR-Pik to engineering of new disease resistance genes. The authors nicely demonstrate that it is indeed possible to engineer resistance proteins with broad recognition specificity for the rice blast fungus. The work is of interest to colleagues in synthetic biology, protein engineering and plant-pathogen interactions.

     (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

5. Human thymopoiesis produces polyspecific CD8+ α/β T cells responding to multiple viral antigens

   This article has 18 authors:

   1. Valentin Quiniou
   2. Pierre Barennes
   3. Vanessa Mhanna
   4. Paul Stys
   5. Helene Vantomme
   6. Zhicheng Zhou
   7. Federica Martina
   8. Nicolas Coatnoan
   9. Michele Barbie
   10. Hang-Phuong Pham
   11. Béatrice Clémenceau
   12. Henri Vie
   13. Mikhail Shugay
   14. Adrien Six
   15. Barbara Brandao
   16. Roberto Mallone
   17. Encarnita Mariotti-Ferrandiz
   18. David Klatzmann

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper reports on important observations regarding human CD8 T cells that express shared T cell receptors amongst individuals and exhibit poly-specificity directed mainly to several unrelated viral antigens. Although the majority of the claims are convincingly supported by results from both in silico and experimental approaches, mechanistic molecular details underlying poly-specificity remain incomplete. The results from these studies will enhance the ongoing debate on T cell specificity and potentially, will impact fields related to immunology, for example, immunoparasitology, cell biology, and vaccine development.

   Reviewed by eLife

6. Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

   This article has 6 authors:

   1. Hongzhe Li
   2. Sandro Bräunig
   3. Parashar Dhapolar
   4. Göran Karlsson
   5. Stefan Lang
   6. Stefan Scheding

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript by Li and coworkers characterizes sorted human non-hematopoietic bone marrow cells by scRNA-seq and predicts their lineage relationships and possible interactions with mature and immature hematopoietic cells. Transcriptionally-different stromal cell subsets are identified, and their lineage relationships, cell-cell interactions and possible specialized functions are inferred or predicted from in-silico studies, paving the way for future functional and validation studies. This resource significantly adds to the current understanding human non-hematopoietic bone marrow stromal cells and their hematopoietic regulatory functions.

     (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

7. Functional gradients in the human lateral prefrontal cortex revealed by a comprehensive coordinate-based meta-analysis

   This article has 4 authors:

   1. Majd Abdallah
   2. Gaston E Zanitti
   3. Valentin Iovene
   4. Demian Wassermann

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     A meta-analysis of over 14,000 fMRI studies revealed a principle rostral-caudal gradient in the lateral prefrontal cortex. This gradient reflected an internal/external axis, which helps to organize the LPFC's involvement in widespread processes from affect, to memory, to control, and action. This is an important contribution to the literature, particularly as a meta-analytic approach has not been applied to this axis of organization and can complement the limitations of single studies. The evidence for the conclusions could be strengthened by ruling out bias in the analysis and drawing a clearer relationship to functional networks.

     (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. 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

9. 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

10. 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