eLife

Latest preprint reviews

1. Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease

   This article has 24 authors:

   1. Conor J Howard
   2. Nathan S Abell
   3. Robert R Warneford-Thomson
   4. Eden Mahdavi
   5. Alan L Su
   6. Carmen Resnick
   7. Nabil Mohammed
   8. Erin M Thompson
   9. Emily R Holzinger
   10. Katrina Catalano
   11. Abhay Hukku
   12. Gabriel A Mintier
   13. Morgan MacKenzie
   14. Bryan L Jiang
   15. Dora Barbosa Rabago
   16. Angela Chan
   17. Carolindah Ntimi
   18. Kaitlyn N Weiler
   19. Stephen C Wilson
   20. Joseph C Maranville
   21. Payal R Sheth
   22. Robert M Plenge
   23. Sriram Kosuri
   24. Diane E Dickel

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important paper presents a rigorous and comprehensive deep mutational analysis of the kinase TYK2, revealing how single amino acid substitutions influence protein abundance, signaling activity, and responses to pharmacological inhibitors. By combining high‑quality experimental design with dose‑response signaling assays and multiple inhibitor conditions, the authors generate a robust dataset that identifies variants across all domains of TYK2, including clusters at functionally critical sites and protein-protein interfaces. The study highlights mutations that drive drug resistance or potentiation and shows that reduced TYK2 abundance aligns with protective autoimmune‑associated variants, underscoring the therapeutic relevance of modulating TYK2 stability. Overall, the work provides compelling insights with clear implications for biochemistry, immunology, clinical genetics, and drug discovery.

   Reviewed by eLife

2. Flexible and high-throughput simultaneous profiling of gene expression and chromatin accessibility in single cells

   This article has 5 authors:

   1. Volker Soltys
   2. Moritz Peters
   3. Dingwen Su
   4. Marek Kučka
   5. Yingguang Frank Chan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a useful methodological advance that better enables the simultaneous measurement of gene expression and chromatin accessibility in individual cells. The evidence supporting the improved detection of gene expression is solid, though the reduced performance in detecting chromatin accessibility represents a limitation. This method will be of interest to those studying transcription and gene regulation.

   Reviewed by eLife

3. Temporal single-cell analysis reveals age-associated delay in immune resolution after respiratory viral infection

   This article has 17 authors:

   1. Yue Wu
   2. Chaofan Li
   3. Jinyi Tang
   4. Xiaochen Gao
   5. In Su Cheon
   6. Bibo Zhu
   7. Ruixuan Zhang
   8. Cori E. Fain
   9. Shengen Shawn Hu
   10. Harish Narasimhan
   11. Gislane de Almeida Santos
   12. Katayoun Ayasoufi
   13. Aaron J. Johnson
   14. Hui Zong
   15. Chongzhi Zang
   16. Haidong Dong
   17. Jie Sun

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents valuable findings that could potentially allow a deeper understanding of the immunopathogenesis underlying influenza infection in aged mice. The results are based on solid evidence that define putative immune determinants underlying immunopathology in the aged lung. This study will be of interest to researchers pursuing aging research, as well as to immunologists.

   Reviewed by eLife

4. A high-throughput assay for the measurement of Ca2+-oscillations and insulin release from uniformly sized β-cell spheroids

   This article has 4 authors:

   1. Stijn Robben
   2. Patricia Davidson
   3. Rita S Rodrigues Ribeiro
   4. Thomas Voets

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this valuable study, Robben et al. describe a 3D beta-cell spheroid platform, a tool allowing high-throughput monitoring of cytoplasmic calcium concentrations and insulin secretion, with calcium signals comparable to those recorded in primary pancreatic islets. The authors demonstrate the method by culturing MIN6 cells in a 3D culture system, and show solid evidence of its utility by recording calcium signals in a high-throughput format and characterizing these calcium signals using pharmacological tools. This highlights the potential utility of the 3D beta-cell spheroids for screening new pharmacological modulators of pancreatic beta-cell function.

   Reviewed by eLife

5. Contractile peri-nuclear actomyosin network repositions peripheral and polar chromosomes to promote early kinetochore–microtubule interactions

   This article has 6 authors:

   1. Nooshin Sheidaei
   2. John K Eykelenboom
   3. Zuojun Yue
   4. Graeme Ball
   5. Alexander JR Booth
   6. Tomoyuki U Tanaka

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study demonstrates that a peri-nuclear actomyosin network, present in some types of human cells, facilitates kinetochore-spindle attachment of chromosomes in unfavorable locations - thereby suppressing their missegregation rate. This actomyosin network and its general role have been studied previously, but this study convincingly clarifies the underlying mechanism using a light-controlled perturbation and detailed tracking of kinetochore movement. The generality of the mechanism could be further supported by confirming the findings in non-synchronized cells and additional cell lines. The results may have implications for understanding chromosome missegregation in cancer cells.

     [Editors' note: this paper was reviewed by Review Commons.]

   Reviewed by eLife, Review Commons

6. Nuclear export governs TDP-43 phase transitions and cytoplasmic aggregation

   This article has 6 authors:

   1. Natalie Chin
   2. Qi Zhang
   3. Jizhong Zou
   4. Ken Chih-Chien Cheng
   5. Wei Zheng
   6. Yihong Ye

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents valuable findings implicating nuclear export in the regulation of protein condensate behaviour and TDP-43 phase behaviour, suggesting a link to pathogenic aggregation in ALS/FTD. However, the research relies extensively on synthetic, non-physiological protein variants and a homozygous disease model, with limited mechanistic validation, leading to conclusions that remain largely correlative. Furthermore, limitations in the reporting of experimental replication and controls, as well as inconsistencies between cancer cell and neuronal models, diminish confidence in the robustness of the findings. Despite its technical strengths, the findings presented are currently incomplete and do not provide sufficient evidence to substantiate claims about the direct role of nuclear export in pathological protein aggregation and disease.

   Reviewed by eLife

7. PKMζ-PKCι/λ double-knockout demonstrates atypical PKC is crucial for the persistence of hippocampal LTP and spatial memory

   This article has 19 authors:

   1. Panayiotis Tsokas
   2. Changchi Hsieh
   3. Alejandro Grau-Perales
   4. Andrew Tcherepanov
   5. Leo Kwok
   6. Laura Melissa Rodriguez-Valencia
   7. David A Cano
   8. Kim D Allen
   9. Hannah JH Smith
   10. Sabina Kubayeva
   11. Benson J Wei
   12. Samuel Sabzanov
   13. Rafael E Flores-Obando
   14. Sourav Ghosh
   15. Peter John Bergold
   16. Jerry Rudy
   17. James E Cottrell
   18. André Antonio Fenton
   19. Todd Charlton Sacktor

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study addresses the unresolved and long-debated question of whether atypical protein kinase C is required for the maintenance of synaptic potentiation and long-term memory. The results confirm previous findings that persistent activity of PKMζ is required for lasting potentiation of hippocampal synapses and spatial memory. The study also adds new genetic evidence to support the earlier suggestion that enhanced expression of PKC iota/lambda compensates for the genetic reduction of PKM zeta to support synaptic potentiation and memory; however, the results as currently presented were viewed as incomplete.

   Reviewed by eLife

8. Constraints on the G1/S transition pathway may favor selection of multicellularity as a passenger phenotype

   This article has 3 authors:

   1. Tom Louis Ducrocq
   2. Damien Laporte
   3. Bertrand Daignan-Fornier

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study implicates that changes in cell regulation may contribute to the evolution of multicellularity. The evidence supporting the conclusions is convincing, with rigorous methods used to test alternative hypotheses. The work will be of broad interest to cell and evolutionary biologists and those studying the cell cycle and cancer.

   Reviewed by eLife

9. Impacts of mutation accumulation and order on tumor initiation revealed by engineered murine colorectal cancer organoids

   This article has 9 authors:

   1. Yanping Li
   2. Xiaoxin Xie
   3. Daqi Deng
   4. Zhiyuan Sun
   5. Zhaoan Huang
   6. Yisen Tang
   7. Liang Fang
   8. Wei Chen
   9. Qionghua Zhu

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a valuable finding on the mutational order for common alterations in colorectal cancer. The evidence of in vitro growth assays comparing mutations is solid, although inclusion of biological replicates for the transcriptional assessments and in vivo experiments would have strengthened the study. The work will be of interest to scientists working in the field of colon cancer.

   Reviewed by eLife

10. Cribriform Plate Microenvironment Assembles a Suppressive Myeloid Network during EAE-induced Neuroinflammation

    This article has 11 authors:

    1. Collin Laaker
    2. Martin Hsu
    3. Andy Madrid
    4. Jenna Port
    5. Sophia M Vrba
    6. Melinda Herbath
    7. Cameron Baenen
    8. Mohan Kumar
    9. Thanthrige Thiunuwan Priyathilaka
    10. Matyas Sandor
    11. Zsuzsanna Fabry

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      Laaker et al. make an important finding that the cribriform plate acts as a unique neuroimmune interface that shapes local myeloid cell states during EAE-induced neuroinflammation. Using immuohistochemistry, flow cytometry, and single-cell RNAseq of doublets to interrogate cell-cell interactions, the authors provide solid evidence that macrophages, migratory dendritic cells (DCs), and fibroblasts interact at the site of CSF outflow, with DCs showing characteristics of immune tolerance. While the functional consequences of these cell states remain to be established, the work shows that the cribiform plate can play a key role in influencing immune cell composition and interactions with stromal cells.

    Reviewed by eLife