eLife

Latest preprint reviews

1. NAD boosting mediated by CD38 inhibition drives reversal of a pathological vicious cycle of intracrine activity and inflammation in eyelid meibomian gland dysfunction

   This article has 8 authors:

   1. Yuki Hamada
   2. Takehide Sakamoto
   3. Daisuke Yarimizu
   4. Hikari Uehara
   5. Xinyan Shao
   6. Tom Macpherson
   7. Emi Hasegawa
   8. Masao Doi

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The authors provide valuable data linking NAD+ dependent HSD3b6 gene expression in the eyelid to a vicious cycle involving decreased steroidogenesis and AR signaling, pro-inflammatory cytokine release, inflammation, CD38 activation, and further NAD+ decline, which induces meibomian gland atrophy leading to dry eye disease. Overall, the presented work provides evidence for the pathologic relationship between a pro-inflammatory environment, intracrine activity, and the NAD+ cofactor. However, the current study does not clearly establish the proposed intracrine mechanism and may largely reflect systemic hormonal effects resulting from the global Had3b6 knockout, leading to an incomplete narrative.

   Reviewed by eLife

2. Fully computational design of PAM-relaxed Staphylococcus aureus Cas9 with expanded targeting capability

   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 provide convincing evidence through rigorous biochemical validation across multiple human cell types, comprehensive deep-sequencing analyses, and direct comparisons with established variants, providing mechanistic insights into PAM specificity remodeling and Cas9 optimization. By establishing computational design as a 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

3. 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

4. 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

5. 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:

     This important study presents a novel and technically robust framework that combines deep learning and optimized patch‑clamp protocols to infer biophysical parameters and generate electrophysiology‑based digital twins, with the inclusion of convincing experimental data being a clear strength; there is methodological innovation and potential impact for understanding cellular heterogeneity, drug response, and arrhythmia risk prediction. Concerns remain about clarity and validation, particularly regarding the biological meaning of the modeled heterogeneity, the selection and sufficiency of large synthetic training populations, and the robustness and uniqueness of inferred parameter sets. Most notably, key translational claims (e.g., replacing large‑scale wet experiments and predicting rare arrhythmic events) lack direct experimental validation and head‑to‑head comparisons with conventional protocols. Overall, while the approach is promising and timely, stronger biological grounding, clearer framing, and additional experimental validation are needed to support the manuscript's broad claims.

   Reviewed by eLife

6. 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

7. Single Domain Antibody Inhibitors Target the Coiled Coil Arms of the Bacillus subtilis SMC complex

   This article has 5 authors:

   1. Ophélie 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 authors provide convincing evidence that these nanobodies target the coiled-coil region of the SMC subunit and demonstrate that this region is critical for SMC function in vivo. Overall, the work is significant for the fields of genome organization, SMC protein biology, synthetic biology, and bacterial cell biology.

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

   Reviewed by eLife, Review Commons

8. 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

9. 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

10. 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