eLife

Latest preprint reviews

1. Systematic annotation of a complete adult male Drosophila nerve cord connectome reveals principles of functional organisation

   This article has 23 authors:

   1. Elizabeth C Marin
   2. Billy J Morris
   3. Tomke Stürner
   4. Andrew S Champion
   5. Dominik Krzeminski
   6. Griffin Badalamente
   7. Marina Gkantia
   8. Christopher R Dunne
   9. Katharina Eichler
   10. Shin-ya Takemura
   11. Imaan FM Tamimi
   12. Siqi Fang
   13. Sung Soo Moon
   14. Han SJ Cheong
   15. Feng Li
   16. Philipp Schlegel
   17. Sebastian E Ahnert
   18. Stuart Berg
   19. Janelia FlyEM Project Team
   20. Gwyneth M Card
   21. Marta Costa
   22. David Shepherd
   23. Gregory SXE Jefferis

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This fundamental study provides a near-comprehensive anatomical description and annotation of neurons in a male Drosophila ventral nerve cord, based on large-scale circuit reconstruction from electron microscopy. This connectome resource will be of substantial interest to neuroscientists interested in sensorimotor control, neural development, and analysis of brain connectivity. However, although the evidence is extensive and compelling, the presentation of results in this very large manuscript lacks clarity and concision.

   Reviewed by eLife

2. Human adherent cortical organoids in a multi-well format

   This article has 6 authors:

   1. Mark van der Kroeg
   2. Sakshi Bansal
   3. Maurits A Unkel
   4. Hilde Smeenk
   5. Steven A Kushner
   6. Femke MS de Vrij

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This paper describes an important advance in a 2D in vitro neural culture system to generate mature, functional, diverse, and geometrically consistent cultures, in a 384-well format with defined dimensions and the absence of the necrotic core, which persists for up to 300 days. The well-based format and conserved geometry make it a promising tool for arrayed screening studies. The evidence is compelling and provides a method for generating consistent 3D cortical layer-like organization.

   Reviewed by eLife

3. SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery

   This article has 15 authors:

   1. Viviane Kremling
   2. Sven Falke
   3. Yaiza Fernández-García
   4. Christiane Ehrt
   5. Antonia Kiene
   6. Bjarne Klopprogge
   7. Emilie Scheer
   8. Fabian Barthels
   9. Philipp Middendorf
   10. Sebastian Kühn
   11. Stephan Günther
   12. Matthias Rarey
   13. Henry N Chapman
   14. Dominik Oberthür
   15. Janina Sprenger

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study describes the crystallographic screening of a number of small molecules against a viral enzyme critical for the 5' capping of SARS-CoV-2 RNA and viral replication. While the high-quality crystal structures and complementary biophysical assays in this study provide solid evidence to support the major claims regarding how these small molecule compounds bind to the viral enzyme, the mismatch between the antiviral activity and binding to the viral enzyme of several small molecule compounds could have been more thoroughly investigated or discussed. This paper would be of interest to the fields of coronavirus biology, structural biology, and drug discovery.

   Reviewed by eLife

4. Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ

   This article has 2 authors:

   1. Jinsai Shang
   2. Douglas J Kojetin

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This landmark study elucidates the intricate structural mechanisms by which both covalent and non-covalent synthetic ligands can co-occupy the binding pocket of the nuclear receptor transcription factor PPARγ. Through a compelling integration of structural, biochemical, and biophysical evidence, the authors challenge the reliability of two commonly used covalent inhibitors. These findings have far-reaching implications for the broader field of nuclear receptor research. This work will be of high interest to structural biologists and biochemists exploring ligand interactions within the nuclear receptor superfamily.

   Reviewed by eLife

5. Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons

   This article has 7 authors:

   1. Shun Hiramatsu
   2. Kokoro Saito
   3. Shu Kondo
   4. Hidetaka Katow
   5. Nobuhiro Yamagata
   6. Chun-Fang Wu
   7. Hiromu Tanimoto

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study uses state-of-the-art methods to label endogenous dopamine receptors in a subset of Drosophila mushroom body neuronal types. The authors report that Dop1R1 and Dop2R receptors, which have opposing effects on intracellular cAMP, are present in axons termini of Kenyon cells, as well as those of two classes of dopaminergic neurons that innervate the mushroom body indicative of autocrine modulation by dopaminergic neurons. Additional experiments showing opposing effects of starvation on Dop1R1 and Dop2R levels in mushroom body neurons are consistent with a role for dopamine receptor levels increasing the efficiency of learned food-odour associations in starved flies. Supported by solid data, this is an important contribution to the field.

   Reviewed by eLife

6. Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across five fly Parkinsonism models

   This article has 15 authors:

   1. Ulrike Pech
   2. Jasper Janssens
   3. Nils Schoovaerts
   4. Sabine Kuenen
   5. Carles Calatayud Aristoy
   6. Sandra F Gallego
   7. Samira Makhzami
   8. Gert J Hulselmans
   9. Suresh Poovathingal
   10. Kristofer Davie
   11. Adekunle T Bademosi
   12. Jef Swerts
   13. Sven Vilain
   14. Stein Aerts
   15. Patrik Verstreken

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This is an important study demonstrating that anosmia in Parkinson's disease patients is due to dysfunction in cholinergic neurons. This study provides compelling evidence, using scRNA sequencing, that cholinergic olfactory projection neurons (OPN) are consistently affected in five different fruit fly models of Parkinson's disease, exhibiting synaptic dysfunction before the onset of motor deficits. Comparisons with scRNA sequencing of patients' human brain samples reveals similar synaptic gene deregulation in cholinergic neurons of patients. This study points the possibility that targeting cholinergic neurons could be a potential avenue for early diagnosis and intervention in PD.

   Reviewed by eLife

7. Repression of PRMT activities sensitize human homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment

   This article has 21 authors:

   1. Youyou Zhang
   2. Mu Xu
   3. Jiao Yuan
   4. Zhongyi Hu
   5. Junjie Jiang
   6. Yanrong Sun
   7. Jie Huang
   8. Yuxin Wang
   9. Bingwei Wang
   10. Jianfeng Shen
   11. Meixiao Long
   12. Yi Fan
   13. Kathleen T Montone
   14. Janos Tanyi
   15. Sarah H Kim
   16. Omid Tavana
   17. Robert H Vonderheide
   18. Ho Man Chan
   19. Susan Domchek
   20. Lin Zhang
   21. Xiaowen Hu

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a valuable and interesting finding that a combination of arginine methyltransferase inhibitors synergize with PARP inhibitors to eliminate ovarian and triple negative cancer cell lines in vitro and in vivo using preclinical mouse models. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for the development of novel therapeutics. The work will be of broad interest to scientists working in the field of breast cancer and ovarian cancer.

   Reviewed by eLife

8. Reproducible, data-driven characterization of sleep based on brain dynamics and transitions from whole-night fMRI

   This article has 6 authors:

   1. Fan Nils Yang
   2. Dante Picchioni
   3. Jacco A de Zwart
   4. Yicun Wang
   5. Peter van Gelderen
   6. Jeff H Duyn

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important work, leveraging state-of-the-art whole-night sleep EEG-fMRI methods, advances our understanding of the brain states underlying sleep and wakefulness. Despite a small sample size, the authors present convincing evidence for substates within N2 and REM sleep stages, with reliable transition structure, supporting the perspective that there are more than the five canonical sleep/wake states.

   Reviewed by eLife

9. Learning place cells and remapping by decoding the cognitive map

   This article has 4 authors:

   1. Markus Borud Pettersen
   2. Vemund Schøyen
   3. Anders Malthe-Sørenssen
   4. Mikkel E Lepperød

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This useful modeling study shows how spatial representations similar to experiment emerge in a recurrent neural network trained on a navigation task by requiring path integration and decodability, but without relying on grid cells. The network modeling results are solid, although the link to experimental data may benefit from further development.

   Reviewed by eLife

10. Ligand-coupled conformational changes in a cyclic nucleotide-gated ion channel revealed by time-resolved transition metal ion FRET

    This article has 3 authors:

    1. Pierce Eggan
    2. Sharona E Gordon
    3. William N Zagotta

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This valuable study uses fluorescence lifetime imaging and steady-state and time-resolved transition metal ion FRET to characterize conformational transitions in the isolated cyclic nucleotide binding domain of a bacterial CNG channel. The data are compelling and support the authors' conclusions. The results advance the understanding of allosteric mechanisms in CNBD channels and have theoretical and practical implications for other studies of protein allostery. A limitation is that only the cytosolic fragments of the channel were studied.

    Reviewed by eLife