eLife

Latest preprint reviews

1. The Drosophila EGF domain protein Uninflatable sets the switch between wrapping glia growth and axon wrapping instructed by Notch

   This article has 4 authors:

   1. Marie Baldenius
   2. Steffen Kautzmann
   3. Rita Kottmeier
   4. Christian Klämbt

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study identifies a new key factor in orchestrating the process of glial wrapping of axons in Drosophila wandering larvae. The evidence supporting the claims of the authors is convincing and the EM studies are of outstanding quality. However, the quantification of the wrapping index, the role of Htl/Uif/Notch signaling in differentiation vs growth/wrapping, and the mechanism of how Uif "stabilizes" a specific membrane domain capable of interacting with specific axons might require further clarification or discussion. The work will be of interest to neuroscientists working on glial cell biology.

   Reviewed by eLife

2. Enalapril mitigates aging by targeting antioxidative genes via phosphorylated Smad1/5/9

   This article has 11 authors:

   1. Wencong Lyu
   2. Haochen Wang
   3. Zhehao Du
   4. Ran Wei
   5. Jianuo He
   6. Fanju Meng
   7. Jinlong Bi
   8. Lijun Zhang
   9. Chao Zhang
   10. Yiting Guan
   11. Wei Tao

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The manuscript presents valuable data suggesting that enalapril elevates pSmad1/5/9 signaling, reduces cellular senescence, and enhances physiological functions in aged mice. However, the in vivo evidence remains incomplete, as studies blocking pSmad1/5/9 or using NAC to negate enalapril's purported benefits are lacking, and no lifespan extension data are shown. While in vitro findings support Smad1/5/9 as a key mediator, additional experiments - including BMP receptor inhibition and comprehensive senescence markers - are necessary to validate its essential role in vivo. Overall, the study provides promising insights into enalapril's anti-senescence potential but requires further rigorous investigation to fully substantiate its mechanism and therapeutic impact.

   Reviewed by eLife

3. Compound Mutations in the Abl1 Kinase Cause Inhibitor Resistance by Shifting DFG Flip Mechanisms and Relative State Populations

   This article has 4 authors:

   1. Gabriel Monteiro da Silva
   2. Kyle Lam
   3. David C Dalgarno
   4. Brenda M Rubenstein

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This work uses enhanced sampling molecular dynamics methods to generate potentially useful information about a conformational change (the DFG flip) that plays a key role in regulating kinase function and inhibitor binding. The focus of the work is on the mechanism of conformational change and how mutations affect the transition. The evidence supporting the conclusions is incomplete.

   Reviewed by eLife

4. Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice

   This article has 9 authors:

   1. Laura S Kremer
   2. Guanbin Gao
   3. Giovanni Rigoni
   4. Roberta Filograna
   5. Mara Mennuni
   6. Rolf Wibom
   7. Ákos Végvári
   8. Camilla Koolmeister
   9. Nils-Göran Larsson

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This is an important study that examines the role of TFAM, a protein that helps maintain mtDNA, in mtDNA mutator mice. With convincing evidence, the authors have demonstrated that TFAM's counteractive role in mtDNA mutator mice is tissue-specific. The study does a thorough job of assessing the impact of modulating TFAM levels in a polg mutator mouse model of aging. The authors have thoroughly addressed all the points raised during the first round of review.

   Reviewed by eLife

5. Synthetic gene circuits that selectively target RAS-driven cancers

   This article has 3 authors:

   1. Gabriel Senn
   2. Leon Nissen
   3. Yaakov Benenson

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study demonstrates the potential of synthetic gene circuits to detect and target aberrant RAS activity in cancer cell lines. The circuit design is novel and the evidence supporting the claims is convincing. As a proof-of-concept, this will be of broad interest. Testing the system with other KRAS mutations and clinically relevant output proteins, as well as gaining a better understanding of the underlying molecular mechanism, will both strengthen the study and help translate the technology toward clinical applications in cancer therapeutics.

   Reviewed by eLife

6. Interpreting prediction intervals and distributions for decoding biological generality in meta-analyses

   This article has 5 authors:

   1. Yefeng Yang
   2. Daniel WA Noble
   3. Alistair M Senior
   4. Malgorzata Lagisz
   5. Shinichi Nakagawa

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This useful study provides a novel perspective on assessing the generalizability of meta-analytic findings by introducing prediction intervals (and distributions) as tools to evaluate whether future studies will likely yield non-zero effects. The methodology is generally solid, with a thorough exploration of a large set of published meta-analyses that broadens our understanding of between-study heterogeneity. However, some critical details are incomplete, requiring refinement to ensure statistical rigor.

   Reviewed by eLife

7. Genome Restructuring around Innate Immune Genes in Monocytes in Alcohol-associated Hepatitis

   This article has 7 authors:

   1. Adam Kim
   2. Megan R McMullen
   3. Annette Bellar
   4. David Streem
   5. Jaividhya Dasarathy
   6. Nicole Welch
   7. Srinivasan Dasarathy

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The manuscript addresses the 3D chromatin architecture in monocytes from patients with alcohol-associated hepatitis and its relationship to enhanced transcription of innate immune genes. While the concept and methodological approach are appealing, the evidence is incomplete as a result of insufficient sample sizes as well as other significant analytical concerns.

   Reviewed by eLife

8. Bridging the Gap in Cancer Cell Behavior Against Matrix Stiffening: Insights from a Trizonal Model

   This article has 6 authors:

   1. Mohammad E Torki
   2. Fan Liu
   3. Rongguang Xu
   4. Yunfeng Chen
   5. Jeffery Fredberg
   6. Zi Chen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a valuable nonlinear mathematical model that addresses how cell shape transitions in response to ECM stiffness. The evidence supporting the claims of the authors is solid, although additional work is required to improve the manuscript. For instance, the authors should improve the overall readability of the text and amend the experimental validation section. The work will be of interest to scientists working on a spectrum of fields including cell mechanics, cell behaviors, and cancer research.

   Reviewed by eLife

9. Structure of METTL3-METTL14 with an m6A nucleotide reveals insights into m6A conversion and sensing

   This article has 12 authors:

   1. Shan Qi
   2. Abhay Kumar
   3. Shuang Chen
   4. Shuo Zhou
   5. Manish Parihar
   6. Carmen Villalobos
   7. Navom Gupta
   8. Siu-Hong Chan
   9. Manjeet K Rao
   10. Stanton F McHardy
   11. Shozeb Haider
   12. Yogesh K Gupta

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The manuscript by Qi et al. provides valuable insights into the structural basis of RNA methylation by the METTL3-METTL14 complex, revealing a novel cryptic pocket critical for m6A recognition. The solid experimental approach, integrating crystallography, molecular simulations, and functional assays, supports a proposed two-step mechanism for enzymatic activity. Refining structural data and addressing binding kinetic inconsistencies would further enhance clarity and impact. This manuscript will interest researchers in RNA modification, cancer biology, and therapeutic drug development.

   Reviewed by eLife

10. DGKα and ζ Deficiency Causes Regulatory T-Cell Dysregulation, Destabilization, and Conversion to Pathogenic T-Follicular Helper Cells to Trigger IgG1-Predominant Autoimmunity

    This article has 10 authors:

    1. Lei Li
    2. Hongxiang Huang
    3. Hongxia Wang
    4. Yun Pan
    5. Huishan Tao
    6. Shimeng Zhang
    7. Peer WF Karmaus
    8. Michael B Fessler
    9. John W Sleasman
    10. Xiao-Ping Zhong

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This study presents a valuable finding on the signaling mechanisms underlying Treg cell homeostasis by identifying the simultaneous requirement of diacylglycerol (DAG) kinases (DGK) alpha and zeta for Foxp3+ Treg cell function and follicular responses, with implications for the pathogenesis of some autoimmune diseases. Whereas data based on the characterization of double knock-out mice (for DGK alpha and zeta) is solid, showing the emergence of autoimmune manifestations, the study has gaps in its experimental approaches since it is not clear what can be attributed to the simultaneous DKGα and ζ deficiency, versus the individual deficiency of either one. Experiments on the pathogenic potential of the DKO Tregs in the absence of other T-cells were not presented and results on the role of CD25 downregulation and CD28-independent activation of Treg cells were not properly discussed. Nonetheless, the reported data would be of interest to immunologists working on T-cell intracellular signaling and autoimmunity.

    Reviewed by eLife