eLife

Latest preprint reviews

1. Analysis of cancer mutations introduced into the Drosophila Notch Negative Regulatory Region uncovers a diversity of regulatory outcomes

   This article has 2 authors:

   1. Hideyuki Shimizu
   2. Martin Baron

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.

   Reviewed by eLife

2. Role of tankyrase scaffolding in the β-catenin destruction complex and WNT signaling

   This article has 17 authors:

   1. Qian Wang
   2. Liping Li
   3. Lin You
   4. Shuai Wang
   5. Lei Han
   6. Bingnan Wang
   7. Liping Yao
   8. Yong Lu
   9. Ilgen Mender
   10. Ann M Flusche
   11. Chiho Kim
   12. Nageswari Yarravarapu
   13. Andrew Lemoff
   14. Lawrence Lum
   15. Jerry W Shay
   16. Yonghao Yu
   17. Chuo Chen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.

   Reviewed by eLife

3. Genomic privacy risks in GWAS summary statistics

   This article has 3 authors:

   1. Ao Lan
   2. Yudi Pawitan
   3. Xia Shen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

   Reviewed by eLife

4. Genomic privacy risks in GWAS summary statistics

   This article has 3 authors:

   1. Ao Lan
   2. Yudi Pawitan
   3. Xia Shen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

   Reviewed by eLife

5. Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switch

   This article has 13 authors:

   1. Shivam Shukla
   2. Jessica A Cross
   3. Monika Kish
   4. Sathish KN Yadav
   5. Johannes F Weijman
   6. Laura O'Regan
   7. Judith Mantell
   8. Ufuk Borucu
   9. Xiyue Leng
   10. Christiane Schaffitzel
   11. Jonathan J Phillips
   12. Derek N Woolfson
   13. Mark P Dodding

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The revised manuscript by Shukla et al. provides important mechanistic insights into kinesin-1 autoinhibition and cargo-mediated activation. Through a convincing integration of protein engineering, computational modeling, biophysical assays, HDX-MS, and electron microscopy, the study delineates how cargo binding induces an allosteric transition that propagates along the coiled-coil stalk to the motor domains, enhancing MAP7 engagement. The revisions substantially improve clarity, figure annotation, and methodological transparency, leaving the remaining limitations, primarily those inherent to conformational heterogeneity and resolution, appropriately acknowledged. Overall, the updated manuscript presents a coherent mechanism for kinesin-1 activation that will be of broad interest to the motor protein, structural biology, and cell biology communities.

   Reviewed by eLife

6. UV irradiation alters TFAM binding specificity and compaction of DNA

   This article has 15 authors:

   1. Dillon E King
   2. Emily E Beard
   3. Matthew J Satusky
   4. Alex George
   5. Ian Ryde
   6. Caitlin Johnson
   7. Emma L Dolan
   8. Yuning Zhang
   9. Wei Zhu
   10. Hunter Wilkins
   11. Evan Corden
   12. Susan K Murphy
   13. Dorothy A Erie
   14. Raluca Gordân
   15. Joel Meyer

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Mitochondrial DNA (mtDNA) exhibits a degree of resistance to mutagenesis under genotoxic stress, and this study on the mitochondrial Transcription Factor A (TFAM) presents important data concerning the possible mechanisms involved. The presented data are solid, technically rigorous, and consistent with established literature findings. The experiments are well-executed, providing convincing evidence on the change of TFAM-DNA interactions following UVC irradiation.

   Reviewed by eLife

7. Interplay between cohesin and TORC1 links chromosome segregation and gene expression to environmental changes

   This article has 11 authors:

   1. Dorian Besson
   2. Sabine Vaur
   3. Stéphanie Vazquez
   4. Sylvie Tournier
   5. Yannick Gachet
   6. Adrien Birot
   7. Stéphane Claverol
   8. Adèle L Marston
   9. Anastasios Damdimopoulos
   10. Karl Ekwall
   11. Jean-Paul Javerzat

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study presents a compelling link between nutrient signaling and chromosome regulation, demonstrating that reduced activity in a central nutrient-sensing pathway improves chromosome stability and alters gene expression through effects on cohesin. The convincing evidence from a combination of genetic, biochemical and cell biological approaches supports a model in which TORC1-dependent phosphorylation of Mis4 and the cohesin subunit Psm1/Smc1 can modulate cohesin loading to enhance faithful chromosome transmission. While the underlying mechanisms and biological importance of this newly described circuit are not yet fully known, the overall body of evidence is strong and supports the main conclusions.

   Reviewed by eLife

8. Multi-barrier unfolding of the double-knotted protein, TrmD–Tm1570, revealed by single-molecule force spectroscopy and molecular dynamics

   This article has 8 authors:

   1. Fernando Bruno da Silva
   2. Szymon Niewieczerzal
   3. Iwona Lewandowska
   4. Mateusz Fortunka
   5. Maciej Sikora
   6. Laura-Marie Silbermann
   7. Katarzyna Tych
   8. Joanna I Sulkowska

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is convincing, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.

   Reviewed by eLife

9. Investigation of All Disease-Relevant Lysine Acetylation Sites in α-Synuclein Enabled by Non-canonical Amino Acid Mutagenesis

   This article has 15 authors:

   1. Marie Shimogawa
   2. Ming-Hao Li
   3. Grace Shin Hye Park
   4. Jennifer Ramirez
   5. Hudson Lee
   6. Paris R Watson
   7. Swati Sharma
   8. Zongtao Lin
   9. Chao Peng
   10. Virginia M.-Y Lee
   11. Benjamin A Garcia
   12. David W Christianson
   13. Elizabeth Rhoades
   14. David Eliezer
   15. E James Petersson

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable work provides new insights into the role of lysine acetylation of alpha-synuclein, the protein involved in Parkinson's Disease. The evidence is mostly solid, but the claims around the potential disease relevance based on seeding assays and structural work need to be toned down, or else supported by additional experimental evidence. Overall, the work will be of interest to researchers in the fields of protein biophysics and post-translational modifications, as well as Parkinson's Disease.

   Reviewed by eLife

10. Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels

    This article has 9 authors:

    1. Michael J Davis
    2. Hae Jin Kim
    3. Min Li
    4. Jorge A Castorena-Gonzalez
    5. Soumiya Pal
    6. Timothy L Domeier
    7. Joshua P Scallan
    8. Scott Earley
    9. Scott D Zawieja

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.

    Reviewed by eLife