eLife

Latest preprint reviews

1. Decoding molecular mechanisms for loss-of-function variants in the human proteome

   This article has 3 authors:

   1. Matteo Cagiada
   2. Nicolas Jonsson
   3. Kresten Lindorff-Larsen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This work introduces FunC-ESMs, a proteome-scale framework to classify loss-of-function missense variants into distinct mechanistic groups by combining two complementary state-of-the-art machine learning models. The strength of evidence is convincing, supported by solid benchmarking, integration with experimental datasets, and careful methodological design. The significance of the findings is valuable, providing a resource of clear interest to researchers and diagnostic laboratories working on variant interpretation.

   Reviewed by eLife

2. CellCover Defines Marker Gene Panels Capturing Developmental Progression in Neocortical Neural Stem Cell Identity

   This article has 8 authors:

   1. Lanlan Ji
   2. An Wang
   3. Shreyash Sonthalia
   4. Seungmae Seo
   5. Daniel Q Naiman
   6. Laurent Younes
   7. Carlo Colantuoni
   8. Donald Geman

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study offers a valuable methodological advance by introducing a gene panel selection approach that captures combinatorial specificity to define cell identity. The findings address key limitations of current single-gene marker methods. The evidence is compelling, but would be strengthened by further validation of rare cell states and unexpected marker categories.

   Reviewed by eLife

3. Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury

   This article has 7 authors:

   1. Yaying Zhu
   2. Chengxiang Deng
   3. Bo Chen
   4. Jia He
   5. Yanan Liu
   6. Cheng Peng
   7. Zhao Shan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury; using spatial transcriptomics, mechanistic perturbations, and functional assays, the authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival during APAP-induced hepatotoxicity. The idea that distinct intrahepatic zones mount tailored stress responses is conceptually significant and has implications for regeneration and toxicology. The dataset is rich and the methodology modern, but several conclusions rely on assumptions about zonation under injury, limited injury models, and incomplete functional validation of the Atf4-Chop-Btg2 axis. With targeted revisions and additional experiments, the work has the potential to provide strong mechanistic insights into liver zonation and injury responses.

   Reviewed by eLife

4. Blocking Osteoprotegerin Reprograms Cancer Associated Fibroblast to Promotes Immune Infiltration into the Tumor Microenvironment

   This article has 12 authors:

   1. Yao Wang
   2. Hara Apostolopoulou
   3. Im Hong Sun
   4. Arjan Bains
   5. David Gibbs
   6. Sui Huang
   7. Tamara Alliston
   8. Ajay Maker
   9. Thea Tlsty
   10. Vasilis Ntranos
   11. James M Gardner
   12. Anil Bhushan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents an important finding by identifying OPG as a novel stromal checkpoint influencing T-cell anti-tumor responses, thereby shedding new light on the complex interplay between the tumor microenvironment and immune regulation. The data are robust and the experimental approaches are sound, providing solid support for the study's conclusions; however, there are a number of additional questions raised by the data. Of particular note are the questions raised on the mechanistic effects of TRAIL versus RANKL. In addition, it would broaden the interest in this study to include more translational human data to complement the work presented.

   Reviewed by eLife

5. Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation

   This article has 8 authors:

   1. Dana MS Cheung
   2. Momchil Razsolkov
   3. Fabrizia Bonacina
   4. Stephen Andrews
   5. Megan Sumoreeah
   6. Linda V Sinclair
   7. Andrew JM Howden
   8. J Simon C Arthur

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This work reveals metabolic pathways and molecular events mechanistically linked to B cell activation. Using an unbiased, comprehensive proteome profiling method and various functional validation approaches, this study generated convincing evidence suggesting a role for amino acid uptake, cholesterol accumulation, and protein prenylation in the proliferation, survival, and biogenesis of B cells stimulated with LPS and other activating stimuli. The significance of the findings is considered to be fundamental, in that they will advance our understanding of cell metabolism during B cell activation.

   Reviewed by eLife

6. Evolution of a fuzzy ribonucleoprotein complex in viral assembly

   This article has 15 authors:

   1. Huaying Zhao
   2. Tiansheng Li
   3. Sergio A Hassan
   4. Ai Nguyen
   5. Siddhartha AK Datta
   6. Guofeng Zhang
   7. Camden Trent
   8. Agata M Czaja
   9. Di Wu
   10. Maria A Aronova
   11. Kin Kui Lai
   12. Grzegorz Piszczek
   13. Richard D Leapman
   14. Jonathan W Yewdell
   15. Peter Schuck

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This is a valuable study that combines biophysical and evolutionary approaches to understand why particular mutations in the SARS-CoV-2 protein N arose during the COVID-19 pandemic. The evidence is solid and supports the conclusions.

   Reviewed by eLife

7. A recursive pathway for isoleucine biosynthesis arises from enzyme promiscuity

   This article has 4 authors:

   1. Vittorio Rainaldi
   2. Stefano Donati
   3. Sarah D’Adamo
   4. Nico J Claassens

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The study reports a potential pathway for isoleucine biosynthesis mediated by the underground activity of AHASII, which converts glyoxylate and pyruvate to 2-ketobutyrate. While the findings are valuable in revealing a possible alternative route for isoleucine production, the evidence presented remains incomplete. More comprehensive biochemical experiments are required to substantiate the physiological feasibility of this pathway.

   Reviewed by eLife

8. Acetylation of H3K115 is associated with fragile nucleosomes at CpG island promoters and active regulatory sites

   This article has 10 authors:

   1. Yatendra Kumar
   2. Dipta Sengupta
   3. Elias T Friman
   4. Robert S Illingworth
   5. Manon Soleil
   6. Zheng Fan
   7. Hua Wang
   8. Kristian Helin
   9. Matthieu Gerard
   10. Wendy A Bickmore

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The reviewers have found that this manuscript is a valuable contribution, and the evidence in support of its conclusions is mostly solid. It provides novel insights and raises interesting possibilities about the functions of an understudied histone modification within the nucleosome core; however, the data are mostly descriptive and correlative, and although this has value, it is not totally persuasive. Short of additional non-genomic experiments, a more detailed analysis of the genomic data and perhaps additional data would strengthen the conclusions. The manuscript crucially needs further antibody validation to raise confidence in the data.

   Reviewed by eLife

9. Toward Robust Neuroanatomical Normative Models: Influence of Sample Size and Covariates Distributions

   This article has 5 authors:

   1. Camille Elleaume
   2. Bruno Hebling Vieira
   3. Dorothea L Floris
   4. Nicolas Langer
   5. the Australian Imaging Biomarkers and Lifestyle flagship study of ageing

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important manuscript evaluates how sample size and demographic balance of reference cohorts affect the reliability of normative models. The evidence supporting the conclusions is convincing, although some additional analysis and clarifications could improve the generalisability of the conclusions. This work will be of interest to clinicians and scientists working with normative models.

   Reviewed by eLife

10. Distinct cortical encoding of acoustic and electrical cochlear stimulation

    This article has 8 authors:

    1. Ariel Edward Hight
    2. Michele N Insanally
    3. Julia K Scarpa
    4. Yew-Song Cheng
    5. Michael Trumpis
    6. Jonathan Viventi
    7. Mario A Svirsky
    8. Robert C Froemke

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This valuable study compares auditory cortex responses to sounds and cochlear implant stimulation measured with surface electrode grids in rats. Beyond the reduced frequency resolution of cochlear implants observed previously, this study suggests key discrepancies between neuronal representations of cochlear stimulations and natural sounds. However, the evidence for this potentially interesting result is incomplete because there is a lack of evidence for the effectiveness of the comparison method. This study is of interest to researchers in the auditory neuroscience field and clinicians implementing treatments with cochlear implants.

    Reviewed by eLife