Evaluated articles

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

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

• 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. After the revision, the authors have addressed most of the concerns and the manuscript has been significantly improved. Both reviewers have agreed on the significance of the work. The work will be of interest to neuroscientists working on glial cell biology.

Reviewed by eLife

Enalapril mitigates senescence and aging-related phenotypes in human cells and mice via pSmad1/5/9-driven antioxidative genes

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

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the anti-senescence effects of enalapril, identifying pSmad1/5/9 signaling and associated antioxidant pathways as key mediators of its physiological benefits in aged mice. The authors present solid experimental evidence across both in vitro and in vivo systems, demonstrating improved organ function and reduced senescence markers following treatment. Overall, the work supports the repurposing potential of enalapril in aging research and expands understanding of its molecular targets.

Reviewed by eLife

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

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

Reviewed by eLife

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

1. Laura Sophie 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

• 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

Synthetic gene circuits that selectively target RAS-driven cancers

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

• 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 to researchers in synthetic biology and therapeutics development, while future work will be required to help translate this technology toward clinical applications in cancer therapeutics and address potential limitations of the strategy.

Reviewed by eLife

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

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

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

• 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

Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss

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

• Curated by eLife

  eLife Assessment

  The preliminary data presented in this manuscript seem valuable. The data are currently incomplete and there are numerous technical concerns, some of which may arise from insufficient description of methodologies used.

Reviewed by eLife

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

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

• 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

Strikingly different neurotransmitter release strategies in dopaminergic subclasses

1. Ana Dorrego-Rivas
2. Darren J Byrne
3. Yunyi Liu
4. Menghon Cheah
5. Ceren Arslan
6. Marcela Lipovsek
7. Marc C Ford
8. Matthew S Grubb

• Curated by eLife

  eLife Assessment

  This study provides evidence for distinct neurotransmitter release modalities between two subclasses of dopaminergic neurons in the olfactory bulb. Specifically, it demonstrates dendritic neurotransmitter release in anaxonic neurons and axonal release in axon-bearing neurons. The presence of GABAergic self-inhibition in anaxonic neurons further underscores the functional divergence between these subtypes. Overall, the manuscript presents solid evidence and offers biologically important insights into the organization and function of dopaminergic circuits within the olfactory bulb.

Reviewed by eLife