eLife

Latest preprint reviews

1. Fully computational design of PAM-relaxed Staphylococcus aureus Cas9 with expanded targeting capability using UniDesign

   This article has 9 authors:

   1. Youcai Xiong
   2. Li-Kuang Tsai
   3. Jun Zhou
   4. Shuang Chen
   5. Xiaofeng Xia
   6. Jifeng Zhang
   7. Y Eugene Chen
   8. Jie Xu
   9. Xiaoqiang Huang

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study demonstrates the power of the UniDesign computational framework in prospectively engineering a PAM-relaxed Staphylococcus aureus Cas9 variant with editing performance comparable to evolution-derived counterparts. The authors responded promptly and thoroughly to reviewer concerns and strengthened the manuscript with additional experimental validation, providing compelling evidence through expanded biochemical characterization across multiple human cell types, comprehensive deep-sequencing analyses, and direct comparisons with established variants that illuminate the mechanistic basis of PAM specificity remodeling and Cas9 optimization. By establishing computational design as a rigorous and viable alternative to directed evolution for CRISPR systems, this work will be of broad interest to the protein engineering, genome engineering, synthetic biology, and computational protein design communities.

   Reviewed by eLife

2. During an inflammatory response, zebrafish tnfa and tnfb are expressed by different cell types and have distinct expression kinetics

   This article has 7 authors:

   1. Kaylee SE van Dijk
   2. Christina Begon-Pescia
   3. Boudewijn A de Bruin
   4. Resul Özbilgiç
   5. Philip M Elks
   6. Mai E Nguyen-Chi
   7. Maria Forlenza

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study provides a valuable contribution to the field of zebrafish immunology by demonstrating that the two TNF paralogs tnfa and tnfb show distinct cellular sources and temporal expression patterns during inflammation. These findings are potentially significant because they suggest regulatory divergence and functional specialization within the TNF signaling system in teleosts. While the evidence supporting differential expression is convincing, the work remains largely observational and would benefit from functional experiments and deeper mechanistic insight to determine whether these differences translate into distinct roles in inflammatory signaling. This work will be of interest to immunologists interested in inflammatory cytokine evolution and immune regulation in vertebrates.

   Reviewed by eLife

3. Chromatin priming and Hunchback recruitment integrate spatial and temporal cues in Drosophila neuroblasts

   This article has 3 authors:

   1. Ayanthi Bhattacharya
   2. Hemalatha Rao
   3. Sonia Q Sen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     The study provides an important advance towards understanding how spatial and temporal transcriptional programs are integrated to regulate lineage-specific chromatin and enhancer activation. The functional evidence is currently incomplete, but the current data provide a solid correlative and conceptual foundation. Functional experiments directly linking Gsb occupancy to chromatin state and regulation of some lineage-specific targets would further strengthen the causal interpretation of the model. Clarifying the scope of conclusions and explicitly acknowledging the technical limitations of current chromatin assays would provide a more balanced interpretation of the manuscript.

   Reviewed by eLife

4. Large-scale synthetic data enable digital twins of human excitable cells

   This article has 7 authors:

   1. Pei-Chi Yang
   2. Mao-Tsuen Jeng
   3. Deborah K Lieu
   4. Regan L Smithers
   5. Gonzalo Hernandez-Hernandez
   6. L Fernando Santana
   7. Colleen E Clancy

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this important study, the authors present an interesting platform for digital twin construction of iPSC-CMs using an AI-based approach. The concept is timely and could have meaningful impact as the field continues to explore integration of computational and experimental models. The evidence is convincing overall, although additional attention to framing and calibration of claims would enhance clarity and better reflect the current level of validation.

   Reviewed by eLife

5. The spike tip protein of bacteriophage T4

   This article has 8 authors:

   1. Yves Mattenberger
   2. Ekaterina S Knyazhanskaya
   3. Mikhail M Shneider
   4. Sergey A Buth
   5. Sergey Nazarov
   6. William P Robins
   7. Petr G Leiman
   8. Dominique Belin

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study by Mattenburger et al. employs structural biology, biochemistry, and genetics to advance understanding of how bacteriophage contractile injection systems mediate host recognition and DNA delivery, yielding a remarkable 1.15 A crystal structure of the T4 spike tip complex (gp5-gp5.4). The compelling evidence presented demonstrates that the spike tip protein gp5.4 is essential for phage fitness and successful infection of Escherichia coli strains bearing truncated lipopolysaccharide; however, direct proof regarding interaction with the cell wall or its components is lacking. The study further provides biochemical evidence that the analogous spike tip protein from phage P2 (GpV) is translocated into the host periplasm during infection, together establishing the spike tip as a critical and active component of the phage infection machinery.

   Reviewed by eLife

6. Single-domain antibody inhibitors target the coiled coil arms of the Bacillus subtilis SMC complex

   This article has 5 authors:

   1. Ophélie J Gosselin
   2. Michael Taschner
   3. Lea M Huber-Hürlimann
   4. Markus A Seeger
   5. Stephan Gruber

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study introduces an innovative synthetic nanobody approach to probe the function of the bacterial SMC complex. The work is a compelling example of the potential of this approach. The authors generate protein chimeras to provide convincing evidence that their identified nanobodies target the coiled-coil region of the SMC subunit, demonstrating that this region is critical for SMC function in vivo. Overall, the work is significant for the fields of genome organisation, SMC protein biology, synthetic biology, and bacterial cell biology.

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

   Reviewed by eLife, Review Commons

7. Leveraging AI to explore structural contexts of post-translational modifications in drug binding

   This article has 3 authors:

   1. Kirill E. Medvedev
   2. R. Dustin Schaeffer
   3. Nick V. Grishin

   Reviewed by eLife

8. In vitro reconstitutions suggest a general model for paradoxical activation of ARAF, BRAF, and CRAF by diverse RAF inhibitor types that does not rely on negative allostery

   This article has 5 authors:

   1. Emre Tkacik
   2. Dong Man Jang
   3. Kayla Boxer
   4. Byung Hak Ha
   5. Michael J Eck

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This paper's biochemical studies of the mechanisms underlying paradoxical activation of RAF family kinases by small-molecule inhibitors have uncovered some important new features of this process by establishing a role for the N-terminal acidic (NtA) motif and showing that CRAF and ARAF can also exhibit paradoxical activation. However, there are substantial criticisms that can be made regarding the data analysis and the evidence for the authors' new model that paradoxical activation does not rely on negative allostery is considered incomplete.

   Reviewed by eLife

9. Single-cell co-mapping reveals relationship between chromatin state and gene expression in early zebrafish development

   This article has 5 authors:

   1. Vivek Bhardwaj
   2. Alberto Griffa
   3. Helena Viñas Gaza
   4. Peter Zeller
   5. Alexander van Oudenaarden

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this valuable study, the authors examine transcription and chromatin dynamics during early zebrafish development by simultaneously profiling histone modifications and full-length transcriptomes in thousands of single cells, providing solid analysis that chromatin and transcriptional states are initially weakly correlated in early embryonic cells and become progressively more aligned as differentiation proceeds. The work also supports a model in which promoter-anchored cis-spreading of H3K27me3 contributes to stable gene silencing during development. Future functional perturbations and orthogonal validations will be needed to determine the causal contribution of Polycomb spreading to fate commitment. Overall, the dataset and accompanying analyses provide a robust resource and a quantitative framework for studying chromatin-transcription relationships during vertebrate embryogenesis.

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

   Reviewed by eLife, Review Commons

10. Engineering ATP Import in Yeast Uncovers a Synthetic Route to Extend Cellular Lifespan

    This article has 11 authors:

    1. Naci Oz
    2. Hetian Su
    3. Vedat Sari
    4. Praveen Patnaik
    5. Rohil Hameed
    6. Jong Hee Song
    7. Derek C Prosser
    8. Vyacheslav M Labunskyy
    9. Vadim N Gladyshev
    10. Nan Hao
    11. Alaattin Kaya

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This manuscript addresses an important and conceptually ambitious question by using a synthetic biology strategy to perturb ATP homeostasis in yeast and examine its causal relationship with lifespan. While the experimental approach and lifespan data are intriguing, the current evidence is incomplete and internally inconsistent, particularly regarding intracellular ATP measurements, transporter directionality, mitochondrial dependence, and the proposed mechanistic model. Substantial clarification, additional controls, and further experimentation will be necessary before the main conclusions can be considered robust and the biological significance of the findings can be fully assessed.

    Reviewed by eLife