eLife

Latest preprint reviews

1. Chemotherapy resistance due to epithelial-to-mesenchymal transition is caused by abnormal lipid metabolic balance

   This article has 8 authors:

   1. Atsushi Matsumoto
   2. Akihito Inoko
   3. Takuya Tanaka
   4. Gen-Ichi Konishi
   5. Waki Hosoda
   6. Takahiro Kojima
   7. Koji Ohnishi
   8. Junichi Ikenouchi

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This paper presents the fundamental discovery that lipid metabolic imbalance induced by Snail, an EMT-related transcription factor, contributes to the acquisition of chemoresistance in cancer cells. The evidence, supported by a wide range of methods and adequate quantification, provides a convincing mechanistic explanation of how Snail drives ectopic expression of the cholesterol- and drug-efflux transporter ABCA1. This work, which introduces a novel therapeutic concept targeting invasive cancer, will be of broad interest to researchers in cancer biology, lipid metabolism, and cell biology.

   Reviewed by eLife

2. High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery

   This article has 18 authors:

   1. Conor J Howard
   2. Nathan S Abell
   3. Beatriz A Osuna
   4. Eric M Jones
   5. Leon Y Chan
   6. Henry Chan
   7. Dean R Artis
   8. Jonathan B Asfaha
   9. Joshua S Bloom
   10. Aaron R Cooper
   11. Andrew Liao
   12. Eden Mahdavi
   13. Nabil Mohammed
   14. Alan L Su
   15. Giselle A Uribe
   16. Sriram Kosuri
   17. Diane E Dickel
   18. Nathan B Lubock

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The authors use deep mutational scanning to assess the effect of ~6,600 protein-coding variants in MC4R, a G protein coupled receptor associated with obesity. They develop new, more precise approaches to deep mutational scanning, enabling them to probe molecular phenotypes directly relevant to the development of drugs that target this receptor. In this important work, the authors provide compelling evidence that variants impact signaling through MC4R in different ways, that some defective variants are amenable to a corrector drug and that deep mutational scanning data could guide compound optimization.

   Reviewed by eLife

3. Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway

   This article has 5 authors:

   1. Lan Yao
   2. Wanwan Zhang
   3. Xiaogang Yang
   4. Meisheng Yi
   5. Kuntong Jia

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The findings in this manuscript are fundamental because they identify an entry receptor MYL3 that belongs to the myosin family as a possible target that could inhibit a virus that has a high impact on aquaculture. The evidence is convincing as it contains strong in vitro and in vivo data that support their conclusions; however, studies on the presence of MYL3 in NNV target tissues will further strengthen their claims

   Reviewed by eLife

4. Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc

   This article has 7 authors:

   1. Changli Zhang
   2. Martha Elena Diaz-Hernandez
   3. Takanori Fukunaga
   4. Sreekala Shenoy
   5. Sangwook Tim Yoon
   6. Lisbet Haglund
   7. Hicham Drissi

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This work demonstrates the therapeutic potential of recombinant human PDGF-AB/BB proteins in alleviating the senescent signatures of primary human intervertebral disc cells. The study represents a fundamental, significant advance in the treatment of intervertebral disc degeneration through the suppression of senescence. The strength of evidence supporting these conclusions is compelling, as it is primarily based on transcriptomic analysis and direct protein measurements from relatively homogeneous cell populations. This work will be of interest to spine basic scientists and clinicians, as well as to musculoskeletal scientists more broadly. The revised manuscript adds greater clarity, and the impact of the study is greatly enhanced.

   Reviewed by eLife

5. Nonlinear transcriptional responses to gradual modulation of transcription factor dosage

   This article has 7 authors:

   1. Júlia Domingo
   2. Mariia Minaeva
   3. John A Morris
   4. Samuel Ghatan
   5. Marcello Ziosi
   6. Neville E Sanjana
   7. Tuuli Lappalainen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important work develops a new protocol to experimentally perturb target genes across a quantitative range of expression levels in cell lines. The evidence supporting their new perturbation approach is convincing, and we propose that focusing on single modality (activation or inhibition) would be sufficient to draw their conclusions. The study will be of broad interest to scientists in the fields of functional genomics and biotechnology.

   Reviewed by eLife

6. Harnessing AlphaFold to reveal hERG channel conformational state secrets

   This article has 5 authors:

   1. Khoa Ngo
   2. Pei-Chi Yang
   3. Vladimir Yarov-Yarovoy
   4. Colleen E Clancy
   5. Igor Vorobyov

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study uses AlphaFold2 to guide the structural modelling of different states of the human voltage-gated potassium channel KV11.1, a key pharmacological drug target. Follow-up molecular dynamics and drug-docking simulations, combined with experimental characterization, offer convincing evidence supporting the models. The work shows potential for improving drug potency predictions in ion channel pharmacology.

   Reviewed by eLife

7. An unusual trafficking domain in MSRP6 defines a complex needed for Maurer’s clefts anchoring and maintenance in P. falciparum infected red blood cells

   This article has 16 authors:

   1. Alexandra Blancke Soares
   2. Jan Stäcker
   3. Svenja Schwald
   4. Wieteke Hoijmakers
   5. Nahla Galal Metwally
   6. Jakob Cronshagen
   7. Hanno Schoeler
   8. Sven Flemming
   9. Katharina Höhn
   10. Ulrike Fröhlke
   11. Paolo Mesén-Ramírez
   12. Bärbel Bergmann
   13. Melissa Khosh-Naucke
   14. Iris Bruchhaus
   15. Richárd Bártfai
   16. Tobias Spielmann

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents valuable data on the identification and function of a protein complex present at the Maurer's cleft organelles of Plasmodium falciparum-infected red blood cells. The evidence supporting the findings is solid, but would benefit from greater rigor in presentation and analysis.

   Reviewed by eLife

8. Effects of residue substitutions on the cellular abundance of proteins

   This article has 2 authors:

   1. Thea K Schulze
   2. Kresten Lindorff-Larsen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is convincing, supported by robust experimental design and comprehensive analyses.

   Reviewed by eLife, PREreview

9. Recombination shapes the diversification of the wtf meiotic drivers

   This article has 6 authors:

   1. Yan Wang
   2. Hao Xu
   3. Qinliu He
   4. Zhiwei Wu
   5. Zhen Gong
   6. Guan-Zhu Han

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study provides one mechanism that can explain the rapid diversification of poison-antidote pairs in fission yeast: recombination between existing pairs. The evidence is largely solid, but the study needs to tune down its claims (as it is not shown that the novel poison-antidote can serve as a meiotic driver), and to address small experimental requests. The work is of interest to scientists studying genetic incompatibilities.

   Reviewed by eLife

10. Change point estimation by the mouse medial frontal cortex during probabilistic reward learning

    This article has 5 authors:

    1. Cayla E Murphy
    2. Hongli Wang
    3. Heather K Ortega
    4. Alex C Kwan
    5. Huriye Atilgan

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This study examined the role of the dorsal medial prefrontal cortex of mice in anticipating reward-value switch points in a two-armed bandit task. They demonstrate the dorsal medial prefrontal cortex is involved in task performance and use model-based methods to uncover the algorithmic processes affected by prefrontal cortex perturbations. If the claims were supported, this would be a valuable finding. Unfortunately, the reviewers recognised significant issues with the task design and analyses, making the evidence to support the role of the prefrontal cortex in anticipation of switches inadequate.

    Reviewed by eLife