eLife

Latest preprint reviews

1. Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

   This article has 5 authors:

   1. Vladislav Belyy
   2. Iratxe Zuazo-Gaztelu
   3. Andrew Alamban
   4. Avi Ashkenazi
   5. Peter Walter

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript reports on a new technical advance in fluorescence microscopy with which changes in the oligomerization of an integral membrane protein can be measured in live cells. The method is used to define the initial steps during activation of the IRE1 signaling arm of the unfolded protein response, leading to the discovery that IRE1 exists as a stable dimer in the absence of stress - which is in contrast to inferences from prior work. In response to stress, the protein assembles into a higher-order oligomer (likely a tetramer), an event that is mediated by the IRE lumenal domain and serves as a prelude to autophosphorylation. While the work will be widely noticed and excitedly discussed in the community, a reconciliation between the different results obtained in this study and in prior work, some of which was reported previously by the same lab, is currently lacking.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

2. Male rat leukocyte population dynamics predict a window for intervention in aging

   This article has 10 authors:

   1. Hagai Yanai
   2. Christopher Dunn
   3. Bongsoo Park
   4. Christopher Coletta
   5. Ross A McDevitt
   6. Taylor McNeely
   7. Michael Leone
   8. Robert P Wersto
   9. Kathy A Perdue
   10. Isabel Beerman

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Yanai et al. used flow cytometry and methlyation profiling to characterize populations of immune cells in the peripheral blood of male rats, finding age-dependent differences in cell composition and DNA methylation profiles, with marked changes occurring at specific time points (e.g., at 15 months and 24 months of age). This raises the possibility that interventions to modify blood aging may be most effective if done prior to these inflection points. This manuscript will be of broad interest to scientists in the geroscience realm and in particular to those using the aging rat as a model for the aging human hematopoietic system.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

3. Transposon mutagenesis in Mycobacterium abscessus identifies an essential penicillin-binding protein involved in septal peptidoglycan synthesis and antibiotic sensitivity

   This article has 8 authors:

   1. Chidiebere Akusobi
   2. Bouchra S Benghomari
   3. Junhao Zhu
   4. Ian D Wolf
   5. Shreya Singhvi
   6. Charles L Dulberger
   7. Thomas R Ioerger
   8. Eric J Rubin

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study reports the results of a transposon inactivation screen to identify essential genes in Mycobacterium abscessus. The authors investigate one hit, the gene encoding the class B penicillin-binding protein, PBP-lipo. They confirm that the PBP-lipo gene is essential despite the presence of a homologous gene and that PBP-lipo is present in other mycobacteria, but not essential in these. They further characterize the consequences of PBP-lipo gene depletion in M. abscessus and demonstrate that the gene product is required for maintaining cell morphology, whilst also participating in a network with other cell wall enzymes. The manuscript will be of interest for researchers working on fundamental aspects of cell wall synthesis in mycobacteria. It may also be relevant for researchers who aim to specifically target M. abscessus using new drugs or drug combinations.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

4. H3K9me1/2 methylation limits the lifespan of daf-2 mutants in C. elegans

   This article has 8 authors:

   1. Meng Huang
   2. Minjie Hong
   3. Xinhao Hou
   4. Chengming Zhu
   5. Di Chen
   6. Xiangyang Chen
   7. Shouhong Guang
   8. Xuezhu Feng

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript examines how putative C. elegans H3K9me methyltransferases affect aging by investigating their effects on long-lived daf-2 mutants. They surprisingly find that modifiers of H3K9me1/2, but not H3K9me3, can synergistically extend the lifespan of daf-2 (in some cases, to three times as long as wild-type). They demonstrate that this synergistic effect on lifespan requires the DAF-16 transcription factor and some of its downstream regulatory targets, and compellingly, they show that the effects on lifespan are phenocopied by a small molecular inhibitor known to target a conserved H3K9me1/2 HMT.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

5. Visceral organ morphogenesis via calcium-patterned muscle constrictions

   This article has 6 authors:

   1. Noah P Mitchell
   2. Dillon J Cislo
   3. Suraj Shankar
   4. Yuzheng Lin
   5. Boris I Shraiman
   6. Sebastian J Streichan

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study employs cutting-edge, multiview light-sheet microscopy and advanced image analysis to investigate how the mechanical interplay of two adjacent tissue layers shapes a developing organ. The finding that genetically-patterned calcium pulses induce local muscle contractions that constrict and fold the adjacent endoderm offers a novel mechanism by which genetically encoded patterning information shapes organs across tissue layers.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

6. Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release

   This article has 5 authors:

   1. Brianna Bibel
   2. Elad Elkayam
   3. Steve Silletti
   4. Elizabeth A Komives
   5. Leemor Joshua-Tor

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper provides well documented and solid biochemical data to show how phosphorylation of AGO2 modulate its binding to target mRNAs, releasing the complex to allow its recycling in the cell via electrostatic repulsion. This result could explain how a small amount of Ago proteins could target a very large number of mRNA molecules . The data support the key claims of the manuscript, and the approaches used are rigorous. This very well-written and elegant study will be of great interest to those working in the miRNA field as it addresses important open questions concerning the dynamic regulation of mIRNA-mediated gene repression.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

7. Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution

   This article has 4 authors:

   1. Spenser S. Smith
   2. Daniel Chu
   3. Tiange Qu
   4. Richard A. Schneider

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Smith et al. examine jaw development across three different species of birds, chick, quail and duck, all of which have jaws of different shapes and sizes. This study provides interesting new data and insights into jaw development and evolution.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

8. Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells

   This article has 16 authors:

   1. Wenyang Li
   2. Jennifer Y Chen
   3. Cheng Sun
   4. Robert P Sparks
   5. Lorena Pantano
   6. Raza-Ur Rahman
   7. Sean P Moran
   8. Joshua V Pondick
   9. Rory Kirchner
   10. David Wrobel
   11. Michael Bieler
   12. Achim Sauer
   13. Shannan J Ho Sui
   14. Julia F Doerner
   15. Jörg F Rippmann
   16. Alan C Mullen

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript by Li et al. identifies the polyether ionophore nanchangmycin as a novel anti-fibrotic compound through a comprehensive chemical library screen. Given the lack of clinically available treatments for liver fibrosis, the anti-activation properties of nanchangmycin could represent a novel therapeutic avenue for the treatment of this disease.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

9. Robotic search for optimal cell culture in regenerative medicine

   This article has 19 authors:

   1. Genki N Kanda
   2. Taku Tsuzuki
   3. Motoki Terada
   4. Noriko Sakai
   5. Naohiro Motozawa
   6. Tomohiro Masuda
   7. Mitsuhiro Nishida
   8. Chihaya T Watanabe
   9. Tatsuki Higashi
   10. Shuhei A Horiguchi
   11. Taku Kudo
   12. Motohisa Kamei
   13. Genshiro A Sunagawa
   14. Kenji Matsukuma
   15. Takeshi Sakurada
   16. Yosuke Ozawa
   17. Masayo Takahashi
   18. Koichi Takahashi
   19. Tohru Natsume

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript by Kanda GN, Natsume T et al. describes a robotic artificial intelligence system with a batch Bayesian optimization algorithm that allows to optimise and reliably repeat cell culture protocols. The authors utilise induced pluripotent stem cell-derived retinal pigment epithelial cells as a model culture system of broad interest in regenerative medicine. They demonstrate that the robotic system with Bayesian algorithm accelerates the optimisation of cell culture protocols and increases the quality and quantity of cell products, compared with manual operations - these results will likely inform and strongly impact modern cell culture strategies in regenerative medicine.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

10. Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells

    This article has 43 authors:

    1. Ana CG Salina
    2. Douglas dos-Santos
    3. Tamara S Rodrigues
    4. Marlon Fortes-Rocha
    5. Edismauro G Freitas-Filho
    6. Daniel L Alzamora-Terrel
    7. Icaro MS Castro
    8. Thais FC Fraga da Silva
    9. Mikhael HF de Lima
    10. Daniele C Nascimento
    11. Camila M Silva
    12. Juliana E Toller-Kawahisa
    13. Amanda Becerra
    14. Samuel Oliveira
    15. Diego B Caetité
    16. Leticia Almeida
    17. Adriene Y Ishimoto
    18. Thais M Lima
    19. Ronaldo B Martins
    20. Flavio Veras
    21. Natália B do Amaral
    22. Marcela C Giannini
    23. Letícia P Bonjorno
    24. Maria IF Lopes
    25. Maira N Benatti
    26. Sabrina S Batah
    27. Rodrigo C Santana
    28. Fernando C Vilar
    29. Maria A Martins
    30. Rodrigo L Assad
    31. Sergio CL de Almeida
    32. Fabiola R de Oliveira
    33. Eurico Arruda Neto
    34. Thiago M Cunha
    35. José C Alves-Filho
    36. Vania LD Bonato
    37. Fernando Q Cunha
    38. Alexandre T Fabro
    39. Helder I Nakaya
    40. Dario S Zamboni
    41. Paulo Louzada-Junior
    42. Rene DR Oliveira
    43. Larissa D Cunha

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      In this paper, the authors demonstrate that the macrophage efferocytic response in SARS-CoV-2 infection is compromised for two reasons. Internalization of apoptotic SARS-CoV-2 infected cells leads to: 1) A proinflammatory as opposed to an anti-inflammatory response; and 2) reduction in macrophage capacity to perform further efferocytosis

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    Reviewed by eLife, ScreenIT