eLife

Latest preprint reviews

1. 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

2. 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 an important 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

3. Social rank-order stability of mice revealed by a novel food competition paradigm in combination with available space competition paradigms

   This article has 3 authors:

   1. Meiqiu Liu
   2. Yue Chen
   3. Rongqing Chen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study proposes a useful assay to identify relative social ranks in mice incorporating the competitive drive for two basic resources - food and living space. Using this new protocol, the authors provide solid evidence of stable ranking among male and female pairs, while reporting more fluctuant hierarchies among triads of males. The evidence is, however, limited by the lack of ethologically based validation, assessment of the influence of competitor recognition, and proof of concept of application to neuroscience. This manuscript may be of interest to those interested in social behavior and related neuroscience.

   Reviewed by eLife

4. Probing the role of synaptic adhesion molecule RTN4RL2 in setting up cochlear connectivity

   This article has 13 authors:

   1. Nare Karagulyan
   2. Maja Überegger
   3. Yumeng Qi
   4. Norbert Babai
   5. Florian Hofer
   6. Lejo Johnson Chacko
   7. Fangfang Wang
   8. Maria Luque
   9. Rudolf Glueckert
   10. Anneliese Schrott-Fischer
   11. Yunfeng Hua
   12. Tobias Moser
   13. Christine Bandtlow

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this work, the authors characterize the synaptic adhesion molecule RTN4RL2, demonstrating its critical involvement in the development and function of auditory synapses between inner hair cells and spiral ganglion neurons. This study is important because it offers potential insights into therapeutic strategies for hearing loss associated with synaptic dysfunction. The findings are solid, because they are supported by the use of multiple advanced techniques, including FISH and SBEM imaging.

   Reviewed by eLife

5. Identification of a sub-population of synovial mesenchymal stem cells with enhanced treatment efficacy in a rat model of osteoarthritis

   This article has 12 authors:

   1. Nedaa Al-Jezani
   2. Asmaa Affan
   3. Catherine Leonard
   4. Nabangshu Das
   5. Luiz Gustavo Almeida
   6. Daniel Young
   7. Anand O Masson
   8. Antoine Dufour
   9. Paul Salo
   10. Pam Railton
   11. James N Powell
   12. Roman J Krawetz

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study characterized and identified clonal MSC populations from human synovium. The authors provide convincing evidence that clonal MSC populations can be isolated and expanded from both normal and osteoarthritic synovium and that CD47 represents a potential marker for improved chondrogenic potential of MSC sub-populations. These findings could provide new avenues for osteoarthritis treatment in the future and deeper mechanistic understanding of the factors involved in the repair.

   Reviewed by eLife

6. R-Spondin Mimetic, SZN-043, Induced Proliferation and Expression of Wnt Target Genes, Two Impaired Features in Human Alcohol-Associated Liver Disease

   This article has 15 authors:

   1. Trevor Fisher
   2. Mehaben Patel
   3. Shalaka Deshmukh
   4. Darshini Shah
   5. Chenggang Lu
   6. Maureen Newman
   7. Jay Ye
   8. Russell Fletcher
   9. Geertrui F Vanhove
   10. Jay Tibbitts
   11. Yang Li
   12. Nicholas J Skill
   13. Zhihong Yang
   14. Suthat Liangpunsakul
   15. Helene Baribault

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study highlights the novel role of RSPO mimetic SZN-043 in the activation of hepatic WNT signaling and promoting hepatocyte regeneration. The authors provide convincing evidence of SZN-043 increasing hepatocytes proliferation in various mouse models, including a humanized mouse liver model, ALD model and CCL4 fibrosis model. This study will be of interest to researchers in liver regeneration and repair mechanisms.

   Reviewed by eLife

7. Acute aerobic exercise intensity does not modulate pain potentially due to differences in fitness levels and sex effects: results from a pharmacological fMRI study

   This article has 3 authors:

   1. Janne Ina Nold
   2. Tahmine Fadai
   3. Christian Büchel

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this valuable study, Nold et al. examined exercise-induced pain modulation in a pharmacological within-subject fMRI study using the opioid-antagonist naloxone and different levels of aerobic exercise intensity and pain. This investigation provides solid evidence to show that the intensity of exercise does not seem to impact the hypoalgesic effect. Moreover, exploratory analysis identified that fitness level and sex may potentially play a role in exercise-induced hypoalgesia, and that further confirmatory studies are required in order to verify these findings.

   Reviewed by eLife

8. Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche

   This article has 18 authors:

   1. Claire Masson
   2. Cyril Scandola
   3. Jean-Yves Rinckel
   4. Fabienne Proamer
   5. Emily Janus-Bell
   6. Fareeha Batool
   7. Naël Osmani
   8. Jacky G Goetz
   9. Léa Mallo
   10. Nathalie Brouard
   11. Catherine Leon
   12. Alicia Bornert
   13. Renaud Poincloux
   14. Olivier Destaing
   15. Alma Mansson
   16. Hong Qian
   17. Maxime Lehmann
   18. Anita Eckly

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment:

     In this revised version, the authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide compelling evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong conclusion is based on the use of state-of-the art techniques such f primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis.

   Reviewed by eLife, preLights

9. Parkinson’s disease-associated Pink1 loss disrupts ensheathing glia and causes dopaminergic neuron synapse loss

   This article has 10 authors:

   1. Lorenzo Ghezzi
   2. Sabine Kuenen
   3. Ulrike Pech
   4. Nils Schoovaerts
   5. Ayse Kilic
   6. Suresh Poovathingal
   7. Kristofer Davie
   8. Jochen Lamote
   9. Roman Praschberger
   10. Patrik Verstreken

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study explores the role of Pink1 in regulating mitochondria-organelle contacts and glial function, advancing our understanding of the mechanisms underlying neurodegenerative diseases. The findings highlight key genes and cellular processes that are critical in maintaining neuronal health, with implications for glial biology and Parkinson's disease research. The methodology and data are solid. This work will be of significant interest to researchers in neuroscience, cell biology, and neurodegenerative diseases.

   Reviewed by eLife

10. Interleukin-4 induces CD11c+ microglia leading to amelioration of neuropathic pain in mice

    This article has 5 authors:

    1. Keita Kohno
    2. Ryoji Shirasaka
    3. Keita Hirose
    4. Takahiro Masuda
    5. Makoto Tsuda

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This study is important as it highlighted how IL-4 regulates the reactive state of a specific microglial population by increasing the proportion of CD11c+ microglial cells and ultimately suppressing neuropathic pain. The study employs a combination of behavioral assays, pharmacogenetic manipulation of microglial populations, and characterization of microglial markers to address these questions. It provided convincing evidence for the proposed mechanism of IL-4-mediated microglial regulation in neuropathic pain.

    Reviewed by eLife