eLife

Latest preprint reviews

1. Evolution of irreversible somatic differentiation

   This article has 4 authors:

   1. Yuanxiao Gao
   2. Hye Jin Park
   3. Arne Traulsen
   4. Yuriy Pichugin

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper will be of interest to researchers working on a broad range of questions in evolutionary biology, from the evolution of multicellularity to senescence and cancer. With their model, the authors study an often-neglected aspect of cellular differentiation and division of labour. While the model is relatively simple, the premise and the findings are thought-provoking and this study can potentially provide the groundwork for further investigation.

     (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 names with the authors.)

   Reviewed by eLife

2. HOXA9 promotes MYC-mediated leukemogenesis by maintaining gene expression for multiple anti-apoptotic pathways

   This article has 8 authors:

   1. Ryo Miyamoto
   2. Akinori Kanai
   3. Hiroshi Okuda
   4. Yosuke Komata
   5. Satoshi Takahashi
   6. Hirotaka Matsui
   7. Toshiya Inaba
   8. Akihiko Yokoyama

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript is of potential interest to experimental haematologists studying initiation and maintenance factors in leukaemia. Overall, the study is well designed and the data is clearly presented. However, in some places the analysis lacks depth and technological sophistication, and the novel insights are limited without additional experimentation.

     (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. A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output in male mice

   This article has 4 authors:

   1. Charlotte Vanacker
   2. R Anthony Defazio
   3. Charlene M Sykes
   4. Suzanne M Moenter

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The study by Vanacker et al examines the effect of activating GFAP expressing cells within the POA and ARC on the activity of GnRH and TAC2 neurons as well as LH levels. The authors found that activation of GFAP POA cells activated GnRH neurons and increased circulating LH levels, limited to intact males. Activation of ARC GFAP cells failed to alter TAC2 activity or LH levels. Inhibition of POA GFAP cells or activation of POA GFAP cells in females failed to alter the firing rate of GnRH neurons. The study is largely well done and clearly presented.

     (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. Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

   This article has 12 authors:

   1. Maren Kasper
   2. Michael Heming
   3. David Schafflick
   4. Xiaolin Li
   5. Tobias Lautwein
   6. Melissa Meyer zu Horste
   7. Dirk Bauer
   8. Karoline Walscheid
   9. Heinz Wiendl
   10. Karin Loser
   11. Arnd Heiligenhaus
   12. Gerd Meyer zu Hörste

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Kasper et al. have analyzed intra-ocular cells in four subjects with HLA-B27-associated acute anterior uveitis, 2 subjects with HLA-B27-negative anterior uveitis, and one subject with bacterial endophthalmitis using several assay techniques including single cell RNA-Seq, fluorescence activated cell sorting, and quantification of multiple cytokines. They discovered a unique pattern in HLA-B27 positive uveitis that exclusively featured plasmacytoid and classical dendritic cells (cDC) infiltrate and plasma cells. These might provide hints for the pathogenesis 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

5. E2F/Dp inactivation in fat body cells triggers systemic metabolic changes

   This article has 10 authors:

   1. Maria Paula Zappia
   2. Ana Guarner
   3. Nadia Kellie-Smith
   4. Alice Rogers
   5. Robert Morris
   6. Brandon Nicolay
   7. Myriam Boukhali
   8. Wilhelm Haas
   9. Nicholas J Dyson
   10. Maxim V Frolov

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Zappia et al investigate the function of E2F transcriptional activity in the development of Drosophila, with the aim of understanding which targets the E2F/Dp transcription factors control to facilitate development. They characterize changes in gene expression by proteomic profiling, and characterize Dp loss phenotypes in muscle, fat body, and the whole body. They document low levels of glycolytic intermediates and circulating trehalose, which is traced to loss of Dp in the fat body. Strikingly, this phenotype and the resulting lethality during the pupal stage (metamorphosis) can be rescued by increasing dietary sugar. Hence the authors provides new insights in the function of E2F/Dp.

     (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 agreed to share their name with the authors.)

   Reviewed by eLife

6. Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace

   This article has 16 authors:

   1. Maren Heimhalt
   2. Alex Berndt
   3. Jane Wagstaff
   4. Madhanagopal Anandapadamanaban
   5. Olga Perisic
   6. Sarah Maslen
   7. Stephen McLaughlin
   8. Conny Wing-Heng Yu
   9. Glenn R Masson
   10. Andreas Boland
   11. Xiaodan Ni
   12. Keitaro Yamashita
   13. Garib N Murshudov
   14. Mark Skehel
   15. Stefan M Freund
   16. Roger L Williams

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study will be of interest to structural biologists, enzymologists, and cell biologists. The kinase complex mTORC1, a master regulator of cell growth, can be inhibited by another protein, DEPTOR. This protein is of general interest for several reasons, including the hope that understanding how DEPTOR works will lead to new strategies for therapeutically tuning mTORC1 activity. This study provides insights into the binding and inhibitory effects of DEPTOR on mTORC1. Solving a few technical questions will improve the work.

     (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 and Reviewer #2 agreed to share their names with the authors.)

   Reviewed by eLife

7. Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates

   This article has 17 authors:

   1. Shan Zhou
   2. Weiwei Wang
   3. Xiaoting Zhou
   4. Yuying Zhang
   5. Yuezheng Lai
   6. Yanting Tang
   7. Jinxu Xu
   8. Dongmei Li
   9. Jianping Lin
   10. Xiaolin Yang
   11. Ting Ran
   12. Hongming Chen
   13. Luke W Guddat
   14. Quan Wang
   15. Yan Gao
   16. Zihe Rao
   17. Hongri Gong

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors have determined the atomic resolution cryo-EM structures of M. tuberculosis cytochrome bcc at 2.7 Å resolution and in complex with anti-tuberculous drugs Q203 at 2.7 Å and TB47 at 2.9 Å resolution. The Q203 compound is a drug candidate otherwise known as Telacebec with promising results in phase 2 clinical trials. The complex structure could pave the way for rational-based drug design.

     (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 agreed to share their name with the authors.)

   Reviewed by eLife

8. Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity

   This article has 9 authors:

   1. Margaret A Myers
   2. Amanda P Smith
   3. Lindey C Lane
   4. David J Moquin
   5. Rosemary Aogo
   6. Stacie Woolard
   7. Paul Thomas
   8. Peter Vogel
   9. Amber M Smith

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This is an interesting synthesis of iterative model development and experimental work in an influenza model of infection in mice. The work is quite groundbreaking in the field as it is the first to use models to link dynamics of lung viral load, infected cells, inflammation, virus-specific CD8+ T cells, bystander CD8+ T cells, and disease status. The paper suggests that CD8+ T cells are vital for elimination of infected cells but can also contribute directly to lung damage and disease severity.

     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 agreed to share their name with the authors.)

   Reviewed by eLife

9. Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel

   This article has 4 authors:

   1. Cathrine Bergh
   2. Stephanie A Heusser
   3. Rebecca Howard
   4. Erik Lindahl

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This article presents molecular dynamics simulations of the pH-gated pentameric ion channel GLIC, which has been the subject of many structural and functional studies. GLIC can be considered as a model system for pentameric ligand-gated ion channels that are responsible for fast chemical-electrical communication between cells in animals. The findings include the solution of open- and closed-like channel forms, intermediates and a "pre-desensitised" state. The approach reproduces modulation by pH and mutation, surprisingly finding a predominance of closed channels, despite activating conditions, and suggest a role for asymmetry in channel gating. Overall, the sampling of channel dynamics is significant and the description of state interconversions sheds new light on pLGIC mechanisms.

     (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

10. P. falciparum K13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites

    This article has 31 authors:

    1. Barbara H. Stokes
    2. Kelly Rubiano
    3. Satish K. Dhingra
    4. Sachel Mok
    5. Judith Straimer
    6. Nina F. Gnädig
    7. Jade R. Bath
    8. Ioanna Deni
    9. Kurt E. Ward
    10. Josefine Striepen
    11. Tomas Yeo
    12. Leila S. Ross
    13. Eric Legrand
    14. Frédéric Ariey
    15. Clark H. Cunningham
    16. Issa M. Souleymane
    17. Adama Gansané
    18. Romaric Nzoumbou-Boko
    19. Claudette Ndayikunda
    20. Abdunoor M. Kabanywanyi
    21. Aline Uwimana
    22. Samuel J. Smith
    23. Olimatou Kolley
    24. Mathieu Ndounga
    25. Marian Warsame
    26. Rithea Leang
    27. François Nosten
    28. Timothy J.C. Anderson
    29. Philip J. Rosenthal
    30. Didier Ménard
    31. David A. Fidock

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This study is of interest to the broad malaria research community and especially those who work on drug resistance. The authors provide a summary of their surveys of African and Southeast Asian Plasmodium falciparum parasites for the Kelch 13 gene, a marker of artemisinin resistance. The contribution of several K13 mutations to artemisinin resistance is investigated in different genetic backgrounds and confirms the lack of a barrier for the potential emergence of artemisinin resistance in African parasites. These findings are of prime importance in the context of public health perspective on managing the risk of resistance appearing in Africa.

      (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