eLife

Latest preprint reviews

1. Molidustat Targets a Synthetic Lethal Vulnerability in APC-Mutant Colorectal Cancer through GSTP1 and PHD2 Co-Inhibition

   This article has 11 authors:

   1. Chiara Asselborn
   2. Agata N. Makar
   3. Jair G. Marques
   4. Aslihan B. Akan
   5. Athanasia Yiapanas
   6. Carrie Jennings
   7. Ana Perez Lopez
   8. Jimi Wills
   9. Asier Unciti Broceta
   10. Kevin B. Myant
   11. Alexander von Kriegsheim

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important paper substantially advances our understanding of how Molidustat may work, beyond its canonical role, by identifying its therapeutic targets in cancer. This study presents a compelling and well-structured investigation into the therapeutic vulnerabilities of APC-mutant colorectal cancer. This work will be of broad interest to the cancer community in studying small molecules and their therapeutic targets.

   Reviewed by eLife

2. Design and experimental characterization of specificity-switching mutational paths of WW domains

   This article has 7 authors:

   1. Ahmed Rehan
   2. Eugenio Mauri
   3. Jorge Fernandez-de-Cossio-Diaz
   4. Pierre-Guillaume Brun
   5. Remi Monasson
   6. Marco Ribezzi-Crivellari
   7. Simona Cocco

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this important study, the authors demonstrate that generative AI techniques (restricted Boltzmann machine) can be used effectively to design and characterize mutational pathways of WW domains with different binding specificities. The computational studies are complemented by experimental validations, and the results provide solid evidence supporting the idea that sequence landscape holds significance in understanding protein evolution from a transition path perspective. The minor weakness of the study in the current form concerns limited success in designing variants with smoothly varying binding specificities. Nevertheless, the work will likely have a major impact on research aimed at understanding how evolution navigates fitness landscapes as well as reconstructing ancestral sequences.

   Reviewed by eLife

3. Separation slang – Laboratory mice use low-frequency call repertoire during physical separation

   This article has 4 authors:

   1. Daniel Breslav
   2. Michal Wojcik
   3. Ursula Koch
   4. Thorsten Becker

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study represents a useful finding on the social modulation of the complex repertoire of vocalizations made across a variety of strains of lab mice. The evidence supporting the claims is, at present, incomplete, as numerous concerns regarding the appropriate categorization of vocalizations, the averaging of data points with disparate levels of occurrence, the interpretation of the function of noisy calls, and a general lack of adequate analyses of experimental data were raised. With these issues addressed, the work will be of importance to scientists studying rodent vocal communication.

   Reviewed by eLife

4. Genetically engineered ESC-derived embryos reveal Vinculin-dependent force responses required for mammalian neural tube closure

   This article has 7 authors:

   1. Ian S. Prudhomme
   2. Eric R. Brooks
   3. Nilay Taneja
   4. Bhaswati Bhattacharya
   5. Brian J. LaFleche
   6. Yasuhide Furuta
   7. Jennifer A. Zallen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript uncovers the importance of Vinculin in the maintenance of junctional integrity during neural tube closure in regions of increased mechanical stress, by using sophisticated methods such as laser ablation and live imaging. The manuscript also reports a novel application of an established embryonic stem cell protocol to efficiently generate mutant and transgenic embryos for analysis. The findings are fundamental in nature, significantly improve our understanding of a major research question, and are backed by compelling evidence. Whilst there is much to appreciate in this work, exactly how Vinculin mediates neural fold elevation remains unclear, and addressing this lacuna will significantly improve the strength of the manuscript; in addition, some rewriting for better clarity (including technical/methodological details) and inclusion of possible consequences of the increased number of tight junction gaps in the vinculin mutant would be pertinent.

   Reviewed by eLife

5. A multi-resolution imaging and analysis pipeline for comparative circuit reconstruction in insects

   This article has 7 authors:

   1. Valentin Gillet
   2. Marcel E Sayre
   3. Griffin S Badalamente
   4. Nicole L Schieber
   5. Kevin Tedore
   6. Jan Funke
   7. Stanley Heinze

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this important study, a new multi-scale imaging workflow promises to accelerate and democratize comparative connectomics, with projectome-level data informing synapse-level connectivity. While the pipeline and time savings are convincing, the evidence for the segmentation methodology as a reusable community resource is incomplete, with key metrics like error rates, annotation times, and proof-reading times not reported. Furthermore, the evidence on the utility of projectome-level information for analysing brains appears misleading. By clarifying the findings and ensuring that the complete software pipeline is available in online open source repositories alongside precise documentation, the authors would deliver on their vision to enable any laboratory to map and analyse brain connectomes.

   Reviewed by eLife

6. Integrated single cell multiomic profiling and functional validation reveal distinct cellular routes to human plasma cell differentiation

   This article has 6 authors:

   1. Colin A Fields
   2. James F Read
   3. Heather Coffman
   4. Edward P Petrow
   5. Anthony Bosco
   6. Deepta Bhattacharya

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     It remains unclear how human antibody-secreting cells (ASCs) differentiate. In this study, the authors discovered a CD30⁺ intermediate subset that appears during the transition from B cells to ASCs, providing a potential ontogeny for extra-germinal center B cell differentiation. This study is useful because it identifies novel intermediate markers that enable tracking of human ASC ontogeny, offering new insights into ASC development. However, the evidence is incomplete, and we see three major limitations: (1) the data are largely representative, requiring additional reproducibility; (2) the bioinformatics analysis is limited; and (3) step-wise phenotypic validation would require lineage-tracing experiments on sorted populations.

   Reviewed by eLife

7. JAK-STAT Pathway Heterogeneity Governs Immunotherapy Response in Breast Cancer

   This article has 5 authors:

   1. Jianbo Zhou
   2. Heng Zhang
   3. Hailin Tang
   4. Lei Yu
   5. Fu Peng

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This multi-omics study provides a comprehensive characterization of the context-dependent roles of the JAK-STAT pathway (JSP) across different cellular compartments within the breast cancer microenvironment. The authors present convincing evidence that high JSP activity paradoxically drives anti-tumor cytotoxicity in T cells but promotes malignancy and immunosuppression in tumor epithelial cells, leading to the fundamental discovery that broad JAK-STAT inhibition could be therapeutically counterproductive. Ultimately, the identification of the immune-related JSP score and the STAT4 axis as predictive biomarkers for anti-PD-1 immunotherapy response, particularly in triple-negative breast cancer, offers critical insights for precise patient stratification and targeted therapeutic interventions.

   Reviewed by eLife

8. The Periaqueductal Gray Selectively Supports Reversal Learning During a Flexible Discrimination Task in Mice

   This article has 5 authors:

   1. Daniela Lichtman
   2. Eyal Bergmann
   3. Jonathan Nicholas
   4. Raphael T Gerraty
   5. Itamar Kahn

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript demonstrates the feasibility and potential value of using functional MRI in awake, behaving mice, enabling assessment of distributed brain activity during ongoing behavior in a manner analogous to human fMRI. The valuable findings suggest that the periaqueductal gray (PAG), a midbrain structure classically linked to threat processing and aversive learning, also contributes to reversal learning. If supported, this result would carry theoretical and practical implications for our subfield by expanding the computational roles attributed to the PAG and motivating cross-species circuit-level investigations. However, the strength of evidence is, at present, incomplete, and several key claims are only partially supported by the current analyses.

   Reviewed by eLife

9. Drowning a frog respiratory rhythm generator in a wash of excitation: State-dependent architecture of a ventilatory oscillator

   This article has 3 authors:

   1. Mufaddal I Baghdadwala
   2. Marina R Sartori
   3. Richard. JA Wilson

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Using isolated frog brainstem preparations, pharmacological manipulation of excitability, systematic extracellular unit mapping, and focal microinjections, this study provides important findings on whether the buccal rhythm generator is a discrete anatomical nucleus or a distributed, state-dependent network. The question is conceptually significant and of interest to researchers working within respiratory neurobiology and rhythmogenicity in general, and the preparation and experimental strategy are generally appropriate. However, the evidence for the strongest architectural claims is incomplete, with pseudoreplication in pooled unit-mapping analyses, inconsistent statistical reporting, and limited controls in necessity/sufficiency experiments. Overall, although data are largely convincing, substantial revision and more nuanced interpretation of the results are required before claims of state-dependent architectural reorganization can be considered well-supported.

   Reviewed by eLife

10. A developmentally regulated long-range enhancer-promoter contact mediates human neural development

    This article has 21 authors:

    1. Devin Bready
    2. Shuai Wang
    3. Niklas Ravn-Boess
    4. Joshua Frenster
    5. Jonathan Sabio
    6. Robert Kushmakov
    7. Finnegan Clark
    8. Adler Guerrero
    9. Cathryn Lapierre
    10. Kristyn Galbraith
    11. Catherine Do
    12. Priscillia Lhoumaud
    13. Jod Prado
    14. Albert Jiang
    15. Sara Haddock
    16. Claire D Kim
    17. Matija Snuderl
    18. Timothée Lionnet
    19. Aristotelis Tsirigos
    20. Jane Skok
    21. Dimitris G Placantonakis

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      In this important study, Bready et al. investigate how a highly conserved long-range enhancer mediates neural-specific SOX2 regulation during neural differentiation using human neural stem cells. This study has broad appeal to developmental neuroscience; however, the data remain incomplete given the need for homozygous enhancer knockouts and biological replicates in the scRNAseq assays.

    Reviewed by eLife