eLife

Latest preprint reviews

1. A miniaturized MR1 metabolite display system with native-like protein features

   This article has 4 authors:

   1. Photis Rotsides
   2. Omkar Shinde
   3. Julia N Danon
   4. Nikolaos G Sgourakis

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The manuscript by Rotsides et al. reports the design and validation of SMART-MR1, a miniaturized MR1 metabolite-display platform in which the α1/α2 ligand-binding domain is stabilized by a synthetic helical domain in place of the α3 domain and β2-microglobulin. Supported by biochemical, biophysical, and structural approaches, including ITC, NMR, and cryo-EM, the work provides solid evidence that SMART-MR1 retains native-like ligand binding and A-F7 TCR recognition while enabling experimental approaches for ligand screening that are difficult with conventional MR1 constructs. The study is valuable for the MR1 and MAIT-cell fields, particularly as a tool for ligand screening and mechanistic studies of MR1-restricted antigen presentation. There are several suggestions to further strengthen the study's impact, including clearer benchmarking against existing MR1 platforms, broader validation across ligands and TCRs, and functional evidence from MAIT-cell staining or activation assays.

   Reviewed by eLife

2. Examining Alzheimer’s Disease modifiable risk factors: Impact of physical activity and diet on neuroanatomy and behaviour in mouse models

   This article has 9 authors:

   1. Cindy L García
   2. Chloe Anastassiadis
   3. Mila Urosevic
   4. Megan Park
   5. Daniel Gallino
   6. Gabriel A Devenyi
   7. Stephanie Tullo
   8. Yohan Yee
   9. M Mallar Chakravarty

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study examines the effects of diet and exercise on brain structure and behaviour in the 3xTg mouse model of Alzheimer's disease. They show that combined access to a low-fat diet and exercise improves regional brain volume and behaviour in transgenic and wild-type control mice in a sex-specific manner, with analyses linking functional improvements to glucose homeostasis. Although some claims are well supported, the overall strength of the evidence is incomplete and hampered by a lack of clarity regarding the statistical analyses chosen. The work may be of interest to researchers studying neurodegenerative disease, particularly in preclinical contexts.

   Reviewed by eLife

3. Uncovering genetic mechanisms underlying trait variation in switchgrass using explainable artificial intelligence

   This article has 12 authors:

   1. Paulo Izquierdo
   2. Xiaoyu Weng
   3. Thomas E Juenger
   4. Jason Bonnette
   5. Yuko Yoshinaga
   6. Chris Daum
   7. Anna Lipzen
   8. Kerrie Barry
   9. Matthew Blow
   10. Melissa D Lehti-Shiu
   11. David B Lowry
   12. Shin-Han Shiu

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The study by Izquierdo and colleagues provides important insights into the field of genomic and transcriptomic prediction of traits across multiple environments. The rationale and analyses conducted to integrate the two types of ~omics datasets across two environments are solid. However, some clarification would be appreciated in the presentation of the results, and adding some statistical control to clarify how the predictors were selected, or assessing their importance using the SHAP framework, would further consolidate the findings.

   Reviewed by eLife

4. Intron Retention Controls Localization of lncRNAs PURPL and MALAT1 to Promote Cell Proliferation and Migration

   This article has 20 authors:

   1. Ioannis Grammatikakis
   2. Chosita Norkaew
   3. You Jin Song
   4. Amit K Behera
   5. Erica C Pehrsson
   6. Corrine Corrina R Hartford
   7. Shreya Kordale
   8. Rishabh Prasanth
   9. Yongmei Zhao
   10. Biraj Shrethsa
   11. Xiao Ling Li
   12. Ravi Kumar
   13. Ragini Singh
   14. Tayvia Brownmiller
   15. Xinyu Wen
   16. Natasha J Caplen
   17. Pablo Perez-Pinera
   18. Kannanganattu V Prasanth
   19. Thomas Gonatopoulos-Pournatzis
   20. Ashish Lal

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript provides important insights into how U2AF2-dependent intron retention regulates the localization and function of long noncoding RNAs, with evidence supported by multiple complementary approaches. The work is notable for linking intron retention to nuclear speckle localization and cellular phenotypes, including proliferation and migration, although the mechanistic basis remains incompletely resolved. Overall, the study presents a compelling dataset with clear biological implications but would benefit from additional analyses to strengthen mechanistic interpretation and generality.

   Reviewed by eLife

5. Bacterial ancestry of the mitochondrial ATP exporter

   This article has 2 authors:

   1. Jotin Gogoi
   2. Rajan Sankaranarayanan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This potentially useful paper presents an intriguing hypothesis about the evolutionary origins of the SLC25 family of mitochondrial carrier proteins common to all eukaryotic life, proposing that all members originated from the ADP/ATP carrier (AAC) and that AAC itself may have emerged from bacterial homologs such as CysZ and YihY. While the phylogenetic analyses and structural searches are reasonable methodologies to explore ancient evolutionary events, the evidence provided here is deemed to provide incomplete support for the conclusion that the mitochondrial ATP transporter is related to CysZ and Yih.

   Reviewed by eLife

6. Decoupling AMPK from fatty acid synthesis allows maintenance of fitness late in life

   This article has 5 authors:

   1. Hanane Hadj-Moussa
   2. Megan Ulusan
   3. Dorottya Horkai
   4. Mohammed Kamran Afzal Mirza
   5. Jonathan Houseley

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study addresses an important question in aging biology by combining metabolic, genetic, and functional approaches to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in shaping distinct aging-associated phenotypes is convincing overall, with the engineered A2A strain providing a particularly elegant demonstration of coordinated metabolic regulation. However, several conclusions would benefit from clarification or moderation, particularly regarding the relationship between late-life fitness and replicative lifespan, the interpretation of "senescence," the proposed existence of distinct aging subpopulations, and the extent to which the data support mechanistic claims about lipid starvation, acetyl-CoA excess, and chromatin-based aging pathways.

   Reviewed by eLife

7. Digest before Ingest: Early Recruitment of Membrane-bound DNaseX to Phagocytic Cups in Macrophages

   This article has 5 authors:

   1. Arghajit Pyne
   2. Vivek Pandey
   3. Subhankar Kundu
   4. Sachie Ikegami
   5. Xuefeng Wang

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This work by Pyne and Pandey et al. addresses DNase X (DNase1L1) activity at the macrophage phagocytic cup, using an innovative imaging approach that couples visualization of cup formation to spatially resolve DNA degradation. The methodology is technically sound, and the central finding that DNA digestion begins prior to phagolysosomal maturation is considered well supported, though some mechanistic claims may benefit from further evidence and more cautious framing. Overall, the study is solid and provides a valuable framework for investigating early events at the phagocytic cup that may shape responses to pathogens and inflammatory disease.

   Reviewed by eLife

8. Capturing learning on the fly: an eye-tracking method to quantify prediction errors and updating the prior

   This article has 5 authors:

   1. Flóra Hann
   2. Cintia Anna Nagy
   3. Zita Olivia Nagy
   4. Dezso Nemeth
   5. Orsolya Pesthy

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a valuable framework that uses anticipatory eye movements to track how expectations are formed and revised during implicit probabilistic sequence learning. The evidence supporting a behavioural dissociation between errors arising from environmental noise and errors reflecting an inaccurate internal model is solid, but the oculomotor data describe behaviour rather than explain the underlying computational mechanisms, and the stronger mechanistic claims - that learning is more repetition-based than error-driven - remain incomplete without formal comparison against computational models of error-driven learning. The emerging reaction-time difference between conditions appears driven by slowing to low-probability stimuli rather than facilitation of high-probability ones, an asymmetry that requires decomposition and consideration of alternative explanations. The potential contamination of the anticipatory measure by starting gaze position should be addressed through control analyses, and the "process-pure" framing should be tempered, given that oculomotor behaviour is itself subject to motor learning.

   Reviewed by eLife

9. Role of desolvation on biomolecular liquid-liquid phase separation

   This article has 4 authors:

   1. Kai Zhang
   2. Zhiyu Peng
   3. Wenfei Li
   4. Wei Wang

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript presents a valuable and timely contribution by incorporating desolvation barriers into coarse-grained models of biomolecular condensates. The findings are convincing, supported by a clear physical model and systematic simulations showing effects on phase behavior, packing, and dynamics. Some clarification and broader context would improve the manuscript, but it provides a foundation that will be of use for developing more realistic coarse-grained interaction schemes.

   Reviewed by eLife

10. Dopaminergic Neurons Linking Threat Processing to Cardiac Modulation and Locomotor Responses

    This article has 5 authors:

    1. Masato Tsuji
    2. Daisuke Jinkoma
    3. Yuki Uemura
    4. Ayako Ogasawara
    5. Kazuo Emoto

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This important study identifies two pairs of dopaminergic neurons (DA-WED) in Drosophila that coordinate cardiac deceleration and locomotor responses to a mechanical threat. The evidence is convincing, supported by comprehensive optogenetic, physiological, and behavioral experiments showing that these neurons are required for and sufficient to drive threat-associated cardiac slowing. The proposed role of cardiac deceleration as an interoceptive contributor to locomotion is intriguing, but should be presented more cautiously, as the causal relationship between heartbeat changes and locomotor output remains less directly established. The work will be of broad interest to those interested in neural circuits, neuromodulation, and the integration of physiological and behavioral responses.

    Reviewed by eLife