eLife

Latest preprint reviews

1. USP28 deletion and small-molecule inhibition destabilizes c-MYC and elicits regression of squamous cell lung carcinoma

   This article has 32 authors:

   1. E Josue Ruiz
   2. Adan Pinto-Fernandez
   3. Andrew P Turnbull
   4. Linxiang Lan
   5. Thomas M Charlton
   6. Hannah C Scott
   7. Andreas Damianou
   8. George Vere
   9. Eva M Riising
   10. Clive Da Costa
   11. Wojciech W Krajewski
   12. David Guerin
   13. Jeffrey D Kearns
   14. Stephanos Ioannidis
   15. Marie Katz
   16. Crystal McKinnon
   17. Jonathan O'Connell
   18. Natalia Moncaut
   19. Ian Rosewell
   20. Emma Nye
   21. Neil Jones
   22. Claire Heride
   23. Malte Gersch
   24. Min Wu
   25. Christopher J Dinsmore
   26. Tim R Hammonds
   27. Sunkyu Kim
   28. David Komander
   29. Sylvie Urbe
   30. Michael J Clague
   31. Benedikt M Kessler
   32. Axel Behrens

   This article has been curated by 1 group:

   • Curated by eLife

     Summary:

     This paper is of general interest to cancer biologists focusing on identifying new targets for cancer therapy particularly in the context of squamous cell lung carcinoma. The authors demonstrate that genetic ablation of the deubiquitinase USP28 reduces the growth of lung squamous cell carcinomas but not lung adenocarcinomas in a mouse model of lung cancer, and that that this restriction of growth is accompanied by loss of expression of several USP28 targets. They also describe activity of a new small molecule compound in controlling the growth of lung squamous cell carcinomas in mouse genetic and xenograft models, and reducing expression of USP28 targets. They demonstrate that USP28 is one target of the newly identified compound, but they do not establish whether it is the only and biologically relevant target of this compound.

     Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

   Reviewed by eLife

2. Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila

   This article has 11 authors:

   1. Myron Barber Child
   2. Jack R Bateman
   3. Amir Jahangiri
   4. Armando Reimer
   5. Nicholas C Lammers
   6. Nica Sabouni
   7. Diego Villamarin
   8. Grace C McKenzie-Smith
   9. Justine E Johnson
   10. Daniel Jost
   11. Hernan G Garcia

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript considers an important open problem in molecular biology, that is how distal chromosomes can recognise each other at a distance and become paired, as happens for example in homolog paring in Drosophila. To address this question, the authors combine theoretical models and experiments, which return valuable insights. However, a final proof of the envisaged mechanisms remains to be determined.

     (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

3. GluA4 facilitates cerebellar expansion coding and enables associative memory formation

   This article has 6 authors:

   1. Katarzyna Kita
   2. Catarina Albergaria
   3. Ana S Machado
   4. Megan R Carey
   5. Martin Müller
   6. Igor Delvendahl

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This work explores the cellular and behavioural effects of a genetically induced reduction of the expression of a glutamate (excitatory) receptor (GluA4), focusing on the cerebellum , a structure involved in the acquisition of arbitrary, complex motor reflexes. The authors show that synaptic transmission at the input layer to the cerebellar cortex is reduced, despite some compensation by other mechanisms, which are characterised. Locomotion is little affected while acquisition of a "conditioned eyeblink" is abolished. The authors try to link the cellular and behavioural phenomena via modelling of the cerebellar computation, although this is not definitive. The work is of high quality, of interest to cerebellar physicists and neurocomputational modellers in particular.

     (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

4. Biosynthesis of a sulfated exopolysaccharide, synechan, and bloom formation in the model cyanobacterium Synechocystis sp. strain PCC 6803

   This article has 5 authors:

   1. Kaisei Maeda
   2. Yukiko Okuda
   3. Gen Enomoto
   4. Satoru Watanabe
   5. Masahiko Ikeuchi

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors have elucidated the biochemical and regulatory apparatus for the biosynthesis of sulfated exopolysaccharides, an entire class of molecules not previously studied in cyanobacteria. The work has broad implications for the microbiology and ecology of these organisms and also opens the possibility to use these compounds in biotechnology and modify their structures by combinatorial synthesis.

     (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

5. Sec17/Sec18 can support membrane fusion without help from completion of SNARE zippering

   This article has 5 authors:

   1. Hongki Song
   2. Thomas L Torng
   3. Amy S Orr
   4. Axel T Brunger
   5. William T Wickner

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This is a very important paper that challenges the generally accepted dogma that full zippering of SNARE complexes is essential for intracellular membrane fusion. Previous work had already shown that C-terminal truncation of one SNARE arrested liposome fusion mediated by the yeast vacuolar SNARE complex and that Sec17/Sec18 could rescue fusion, but it was argued that such rescue could arise because Sec17/Sec18 restored C-terminal zippering. This paper now shows that Sec17/Sec18 rescue fusion even when three SNAREs are crippled -by truncation or mutation- to definitively prevent zippering, thus showing that Sec17/18 have a direct, positive role in membrane fusion.

     (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. Genetic determinants facilitating the evolution of resistance to carbapenem antibiotics

   This article has 10 authors:

   1. Peijun Ma
   2. Lorrie L He
   3. Alejandro Pironti
   4. Hannah H Laibinis
   5. Christoph M Ernst
   6. Abigail L Manson
   7. Roby P Bhattacharyya
   8. Ashlee M Earl
   9. Jonathan Livny
   10. Deborah T Hung

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript is of interest to several fields in biology and medicine including evolutionary genomics and antibiotic stewardship. Ma et al. sought to investigate the breadth of genetic mechanisms for evolution of carbapenem resistance across various lineages of the bacterial pathogen Klebsiella pneumoniae. The authors performed systematic and thorough bioinformatic and genetic analyses to identify how transposon activity and CRISPR-Cas systems facilitate the evolution of antibiotic resistance and restriction of horizontally acquired genetic elements, respectively. The study's results emphasize the importance of additional factors, other than MIC values, such as genetic background, plasmid/transposon activity, and drug identity and choice in determining the rate at which resistance can evolve in K. pneumoniae.

     (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

7. Relish plays a dynamic role in the niche to modulate Drosophila blood progenitor homeostasis in development and infection

   This article has 5 authors:

   1. Parvathy Ramesh
   2. Nidhi Sharma Dey
   3. Aditya Kanwal
   4. Sudip Mandal
   5. Lolitika Mandal

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Mandal and colleagues identified novel functions of the Imd pathway transcription factor Relish in the hematopoietic niche development. The authors found that Relish is required for the maintenance of hematopoietic progenitors downstream of hormonal control. This is the first study showing critical roles of Relish in blood development, and therefore, this study will draw broad attention and contribute to understanding of insect hematopoiesis and immunity.

     (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. Expanding the MECP2 network using comparative genomics reveals potential therapeutic targets for Rett syndrome

   This article has 8 authors:

   1. Irene Unterman
   2. Idit Bloch
   3. Simona Cazacu
   4. Gila Kazimirsky
   5. Bruria Ben-Zeev
   6. Benjamin P Berman
   7. Chaya Brodie
   8. Yuval Tabach

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript has the potential to be of broad interest to neuroscientists who are aiming to leverage concepts and tools of evolutionary biology to identify novel gene targets and much-needed therapeutic interventions. The follow up experiments are detailed, well thought out, and do a good job of proving the potential of the identified drugs in alleviating molecular signatures in in vitro disease models. However, the link between comparative genomic analysis and identification of specific drugs is not yet sufficiently established and doesn't convincingly demonstrate the usability of the evolutionary pipeline in identifying novel therapeutics.

     (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

9. High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast

   This article has 3 authors:

   1. Masak Takaine
   2. Hiromi Imamura
   3. Satoshi Yoshida

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Over the past decade, the role of ATP levels in the material properties of cells has gathered substantial interest in part because of the potential role of ATP in solubilizing biomolecular condensates. This study uses a quantitative imaging-based measurement of ATP levels in live cells to assess the impact of mutants in ATP homeostasis on ATP levels and protein aggregation. The strength of this paper is the quantitative, single cell analysis, and the manipulation of ATP using native control pathways. The authors suggest that fluctuations in ATP concentrations can lead to protein aggregation, which would be of broad interest to many fields, including cell biology, aging and neurodegeneration.

     (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. Two NLR immune receptors acquired high-affinity binding to a fungal effector through convergent evolution of their integrated domain

    This article has 12 authors:

    1. Aleksandra Białas
    2. Thorsten Langner
    3. Adeline Harant
    4. Mauricio P Contreras
    5. Clare EM Stevenson
    6. David M Lawson
    7. Jan Sklenar
    8. Ronny Kellner
    9. Matthew J Moscou
    10. Ryohei Terauchi
    11. Mark J Banfield
    12. Sophien Kamoun

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      Convergent evolution is often observed in nature, but the molecular mechanisms allowing similar functions to independently emerge are rarely understood. This work determines how the high-affinity recognition of a pathogenic effector produced by the rice blast fungus, Avr-PikD, evolved in the immune receptor Pik-1. The integration of molecular evolution analyses with structure-function biochemical testing is novel to the field and the data quality is exceptional. In addition to advancing knowledge of host-microbe co-evolution, this work is exemplary in its transparency and the breadth of approaches utilized to understand protein evolution, and we expect that this study will provide a conceptual framework for similar studies in the future.

      (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, PREreview