eLife

Latest preprint reviews

1. The DBD-α4 helix of EWSR1::FLI1 is required for GGAA microsatellite binding that underlies genome regulation in Ewing sarcoma

   This article has 7 authors:

   1. Ariunaa Bayanjargal
   2. Cenny Taslim
   3. Iftekhar A Showpnil
   4. Julia Selich-Anderson
   5. Jesse C Crow
   6. Stephen L Lessnick
   7. Emily R Theisen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide solid-based evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable insight into the underlying oncogenic mechanisms in Ewing sarcoma, despite the inherent limitations of the some of the techniques used.

   Reviewed by eLife

2. Structural features of heteromeric channels composed of CALHM2 and CALHM4 paralogs

   This article has 3 authors:

   1. Katarzyna Drożdżyk
   2. Martina Peter
   3. Raimund Dutzler

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     In this interesting study, Drożdżyk and colleagues analyze the ability of placental CALHM orthologs to form stable complexes, identifying that CALHM2 and CALHM4 form heterooligomeric channels. The authors then determine cryo-EM structures of heterooligomeric CALHM2 and CALHM4 that reveal a distinct arrangement in which the two orthologs can interact, but preferentially segregate in the channel. This is an important study; the data provide compelling support for the interpretations and overall, the work is clearly described.

   Reviewed by eLife

3. Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer

   This article has 19 authors:

   1. Fei Yue
   2. Amy T Ku
   3. Payton D Stevens
   4. Megan N Michalski
   5. Weiyu Jiang
   6. Jianghua Tu
   7. Zhongcheng Shi
   8. Yongchao Dou
   9. Yi Wang
   10. Xin-Hua Feng
   11. Galen Hostetter
   12. Xiangwei Wu
   13. Shixia Huang
   14. Noah F Shroyer
   15. Bing Zhang
   16. Bart O Williams
   17. Qingyun Liu
   18. Xia Lin
   19. Yi Li

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript presents solid evidence suggesting that the loss of ZNRF3 and RNF43, two E3 ubiquitin ligases, leads to dysregulation of EGFR signaling in cancer. The authors propose that EGFR is a direct substrate of ZNRF3/RNF43. While the authors provide immunoprecipitation data showing increased detection of ubiquitinated species, this evidence does not definitively establish that EGFR itself is ubiquitinated by RNF43/ZNRF3. The absence of direct evidence for EGFR ubiquitination is a major limitation, although the findings are useful as they may provide novel insights into the mechanisms underlying EGFR-driven cancers and open new therapeutic avenues.

   Reviewed by eLife

4. Rab10 regulates neuropeptide release by maintaining Ca2+ homeostasis and protein synthesis

   This article has 8 authors:

   1. Jian Dong
   2. Miao Chen
   3. Jan RT van Weering
   4. Natalia Domínguez
   5. Ka Wan Li
   6. August B Smit
   7. Ruud F Toonen
   8. Matthijs Verhage

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this revised manuscript, Dong et al. investigate the role of the small Ras-like GTPase Rab10 in the exocytosis of DCVs in mouse hippocampal neurons, showing that Rab10 depletion hinders DCV exocytosis independently of its effects on neurite outgrowth. Upon revising their work, these findings provide compelling evidence that Rab10 depletion leads to altered ER morphology, impaired ER-based calcium buffering, and decreased ribosomal protein expression, which collectively contributes to defective DCV secretion. The study comes to the fundamental conclusion that Rab10 is critical for DCV release by ensuring ER calcium homeostasis.

   Reviewed by eLife

5. A neurotransmitter atlas of C. elegans males and hermaphrodites

   This article has 10 authors:

   1. Chen Wang
   2. Berta Vidal
   3. Surojit Sural
   4. Curtis Loer
   5. G Robert Aguilar
   6. Daniel M Merritt
   7. Itai Antoine Toker
   8. Merly C Vogt
   9. Cyril C Cros
   10. Oliver Hobert

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This fundamental study reports the most comprehensive neurotransmitter atlas of any organism to date, using fluorescent knock-in reporter lines. The work is comprehensive, rigorous, and compelling. The tool will be used by broad audience of scientists interested in neuronal cell type differentiation and function, and could be a seminal reference in the field.

   Reviewed by eLife

6. Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia

   This article has 8 authors:

   1. Raji E Joseph
   2. Thomas E Wales
   3. Sandrine Jayne
   4. Robert G Britton
   5. D Bruce Fulton
   6. John R Engen
   7. Martin JS Dyer
   8. Amy H Andreotti

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The manuscript reports on an important comparison of a range of approved clinical inhibitors for BTK used for the treatment of chronic lymphocytic leukemia (CLL). The authors provide compelling evidence for their claims, using a combination of HDX-MS and NMR spectroscopy. The novelty is that this study also seeks to evaluate resistance mutation bias. The manuscript will be of high interest to scientists working on protein drug interactions.

   Reviewed by eLife

7. Ligand response of guanidine-IV riboswitch at single-molecule level

   This article has 3 authors:

   1. Lingzhi Gao
   2. Dian Chen
   3. Yu Liu

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study presents valuable findings on the ligand- and ion-dependent structural dynamics of a transcriptional riboswitch. The single-molecule data presented are solid and prompts intriguing hypotheses and models, which will undoubtedly stimulate future structural analyses. These findings are of considerable interest to biochemists and biophysicists engaged in the study of RNA structure and riboswitch mechanisms.

   Reviewed by eLife

8. Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients

   This article has 15 authors:

   1. Jörn Lötsch
   2. Khayal Gasimli
   3. Sebastian Malkusch
   4. Lisa Hahnefeld
   5. Carlo Angioni
   6. Yannick Schreiber
   7. Sandra Trautmann
   8. Saskia Wedel
   9. Dominique Thomas
   10. Nerea Ferreiros Bouzas
   11. Christian H Brandts
   12. Benjamin Schnappauf
   13. Christine Solbach
   14. Gerd Geisslinger
   15. Marco Sisignano

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     Sisigano et al. report findings about the role of sphingolipids using lipidomics with machine learning in paclitaxel-induced peripheral neuropathy and preliminary translation of the impact of SA1P in cultured neuronal cells. This study presents a valuable finding on the increased activity of two well-studied signal transduction pathways in a subtype of breast cancer. The significance is limited by incomplete evidence which can be addressed in larger clinical cohorts in the future and with more robust biological validation approaches.

   Reviewed by eLife

9. Tgfbr1 regulates lateral plate mesoderm and endoderm reorganization during the trunk to tail transition

   This article has 8 authors:

   1. Anastasiia Lozovska
   2. Ana Casaca
   3. Ana Novoa
   4. Ying-Yi Kuo
   5. Arnon D Jurberg
   6. Gabriel G Martins
   7. Anna-Katerina Hadjantonakis
   8. Moises Mallo

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Morphological characteristics and phenotypes of mutations in key developmental genes suggest that head, trunk, and tail development are regulated by discernible modules. Gdf11 signalling plays a crucial role in orchestrating the transition from trunk to tail tissues in vertebrate embryos. This important study presents convincing evidence that Tgfbr1 acts upstream of Isl1 (a pivotal effector of Gdf11 signalling) and regulates blood vessels, the lateral plate mesoderm, and the endoderm associated with the trunk-to-tail transition. Together with the previous studies, this work identifies a key signal that acts as the pivot of the trunk-to-tail transition.

   Reviewed by eLife

10. ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1

    This article has 17 authors:

    1. Jordina Rincon-Torroella
    2. Marco Dal Molin
    3. Brian Mog
    4. Gyuri Han
    5. Evangeline Watson
    6. Nicolas Wyhs
    7. Shun Ishiyama
    8. Taha Ahmedna
    9. Il Minn
    10. Nilofer Azad
    11. Chetan Bettegowda
    12. Nickolas Papadopoulos
    13. Kenneth W Kinzler
    14. Shibin Zhou
    15. Bert Vogelstein
    16. Kathleen Gabrielson
    17. Surojit Sur

    This article has been curated by 1 group:

    • Curated by eLife

      eLife assessment

      This study presents a valuable finding and developed ME3BP-7 as a novel microencapsulated formulation of 3BP, which specifically targets MCT1-overexpressing PDAC cells. It demonstrates its specificity and efficacy in vitro and in PDAC mouse models, with significant anti-tumor effects and improved serum stability. Overall, the evidence supporting the authors' claims is solid.

    Reviewed by eLife