eLife

Latest preprint reviews

1. Toxin-based screening of C-terminal tags in Escherichia coli reveals the exceptional potency of ssrA-like degrons

   This article has 2 authors:

   1. Patrick C. Beardslee
   2. Karl R. Schmitz

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study employs an innovative genetic selection-based approach to identify short peptide sequences that target bacterial proteins for degradation. Using random mutagenesis they identified 5 amino acid long "degrons" that target the toxin VapC for degradation permitting survival. They provide compelling data that degrons ending in Ala-Ala are selectively recognized by the ClpXP protease and identify the sequence FKLVA as a particularly significant target. As a whole, there is enthusiasm about the author's findings, although there are also some improvements that could be made to increase the clarity and impact, mostly in the form of revisions to the text.

   Reviewed by eLife

2. Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration

   This article has 7 authors:

   1. Debabrata Dey
   2. Shir Marciano
   3. Anna Poryval
   4. Ondřej Groborz
   5. Lucie Wohlrabova
   6. Tomás Slanina
   7. Gideon Schreiber

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This is a valuable study on the diffusion rates of drug molecules in human-derived cells, presenting convincing data indicating that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

   Reviewed by eLife

3. Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy

   This article has 18 authors:

   1. Carlo Giannangelo
   2. Matthew P Challis
   3. Ghizal Siddiqui
   4. Rebecca Edgar
   5. Tess R Malcolm
   6. Chaille T Webb
   7. Nyssa Drinkwater
   8. Natalie Vinh
   9. Christopher Macraild
   10. Natalie Counihan
   11. Sandra Duffy
   12. Sergio Wittlin
   13. Shane M Devine
   14. Vicky M Avery
   15. Tania De Koning-Ward
   16. Peter Scammells
   17. Sheena McGowan
   18. Darren J Creek

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     The manuscript makes an important contribution to antimalarial drug discovery, utilizing diverse systems biology methodologies. It focuses on an improved M1 metalloprotease inhibitor and provides compelling evidence for the utility of chemoproteomics in pinpointing PfA-M1 targeting. Additionally, metabolomic analysis reveals specific alterations in the final steps of hemoglobin breakdown. These findings highlight the potential of the developed methodology not only for PfA-M1 targeting but also for other inhibitors targeting various malarial proteins or pathways.

   Reviewed by eLife

4. The title and authors for this article are not available from our external data provider yet:
   10.48550/arxiv.2403.16382

5. Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

   This article has 13 authors:

   1. Yuedan Wang
   2. Ying Li
   3. Jiaqing Feng
   4. Chuansen Wang
   5. Yuwei Wan
   6. Bingyang Lv
   7. Yinming Li
   8. Hao Xie
   9. Ting Chen
   10. Faxi Wang
   11. Ziyue Li
   12. Anhuai Yang
   13. Xuan Xiao

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     The manuscript establishes a sophisticated mouse model for acute retinal artery occlusion (RAO) by combining unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) with a silicone wire embolus and carotid artery ligation, generating ischemia-reperfusion injury upon removal of the embolus. This clinically relevant model is useful for studying the cellular and molecular mechanisms of RAO. The data overall are solid, presenting a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

   Reviewed by eLife

6. The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modifications in vivo

   This article has 11 authors:

   1. Mengyang Shi
   2. Jie Li
   3. Xiuxiu Liu
   4. Kuo Liu
   5. Lingjuan He
   6. Wenjuan Pu
   7. Wendong Weng
   8. Shaohua Zhang
   9. Huan Zhao
   10. Kathy Lui
   11. Bin Zhou

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

   Reviewed by eLife

7. Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis

   This article has 12 authors:

   1. Luting Yang
   2. Chunqing Hu
   3. Xiaowen Chen
   4. Jie Zhang
   5. Zhe Feng
   6. Yanxin Xiao
   7. Weitai He
   8. Tingting Cui
   9. Xin Zhang
   10. Yang Yang
   11. Yaling Zhang
   12. Yaping Yan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important work describes the activation of astrocytes via the nuclear translocation of PKM2 in an animal model of multiple sclerosis. This study provides convincing evidence of the interaction between TRIM21 and PKM2 as the crucial molecular event leading to the translocation of PKM2 and a metabolic shift towards glycolysis dominance, fostering proliferation in stimulated astrocytes. This finding is significant as it underscores the potential of targeting glycolytic metabolism to mitigate neurological diseases mediated by astrocytes, offering a strong rationale for potential therapeutic interventions.

   Reviewed by eLife

8. Generation of biophysical neuron model parameters from recorded electrophysiological responses

   This article has 5 authors:

   1. Jimin Kim
   2. Minxian Peng
   3. Shuqi Chen
   4. Qiang Liu
   5. Eli Shlizerman

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study is a valuable contribution to the field of neuronal modeling by way of providing a method for rapidly obtaining neuronal physiology parameters from electrophysiological recordings. The method is solid as the generated models reproduce both ground-truth simulated data and empirical data, and there is now a quantitative comparison with other approaches.

   Reviewed by eLife

9. The subthalamic nucleus contributes causally to perceptual decision-making in monkeys

   This article has 3 authors:

   1. Kathryn Branam
   2. Joshua I Gold
   3. Long Ding

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     The fundamental study by Ding and colleagues identifies subpopulations of neurons recorded in the monkey subthalamic nucleus (STN) with distinct activity profiles and causal contributions during perceptual decision-making. The combination of neuronal recording, microstimulation, and computational methods provides convincing evidence for a heterogenous neural population that could support multifaceted roles in decision formation. This study should be of wide interest to computational and experimental neuroscientists interested in cognitive function.

   Reviewed by eLife

10. Microglia aging in the hippocampus advances through intermediate states that drive activation and cognitive decline

    This article has 2 authors:

    1. Jeremy M Shea
    2. Saul A Villeda

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This important work advances our understanding of the aging trajectory and heterogeneity of hippocampal microglia. The authors provide an in-depth characterization of microglia in young and old mice as well as at intermediate time points, which reveals the existence of intermediate states characterized by a distinct transcriptional signature. The experimental approach is solid, especially with the validation of scRNA-seq findings with other methods. The study should be of interest to neuroimmunologists and biologists interested in aging

    Reviewed by eLife