eLife

Latest preprint reviews

1. Integron activity accelerates the evolution of antibiotic resistance

   This article has 3 authors:

   1. Célia Souque
   2. José Antonio Escudero
   3. R Craig MacLean

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: In this manuscript, the authors test the long-standing "evolution-on-demand" hypothesis of integrons. Using a combination of genetic construction work, experimental evolution, and WGS the authors present a convincing body of work favoring the presented hypothesis. They introduce three antibiotic gene cassettes into an integron and use an "evolutionary ramp" approach with gentamicin and demonstrate that the gentamicin resistance cassette shuffles towards the start of the integron. This provides compelling evidence favoring the evolutionary effects of an active class 1 integrase.

     The paper is clear, well written and demonstrates neatly the benefits of integron shuffling. The authors should also be given credit for including experimental data from an integron containing a clinical plasmid including resistance cassettes to the last resort antibiotics carbapenems. This is largely missing in the field.

     Our overall assessment of the manuscript is positive. However, a number of questions have been raised regarding the mechanistic aspects and conclusions of the paper. We are therefore suggesting additional assays to measure phenotypic effects of evolved integrons, and possibly data analyses on the negative controls. If these are not possible to perform, the main conclusions could be slightly altered instead to focus more on the genomics. Finally, we provide some suggestions on making the discussion more balanced and in clarifying the role of chromosomal mutations in the integron-facilitated evolution.

   Reviewed by eLife

2. In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

   This article has 8 authors:

   1. Juan Carlos Jado
   2. Michelle Dow
   3. Krypton Carolino
   4. Adam Klie
   5. Gregory J. Fonseca
   6. Trey Ideker
   7. Hannah Carter
   8. Elizabeth A. Winzeler

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: The authors examined the genomic basis of resistance evolution in human chronic myelogenous leukemia (CML) near-haploid cell lines to 5 separate chemotherapeutic agents.

     Using either whole genome or whole exome analysis, they found numerous instances of single nucleotide polymorphisms and copy number variants, including amplifications and deletions, among lines. They then used subsequent knockdown or knockout experiments to confirm that these variants, in fact, lead to increased resistance in these lines.

     The work is interesting, timely, and has potential clinical implications. For example, the resistance alleles identified here could be closely examined in future studies in order to develop treatment strategies. However, the experimental design has certain limitations, advances in understanding chemotherapy resistance mechanisms is currently modest, and the presentation of results can be improved. We feel overall that these could be addressed, but that they will require significant extra experimental work.

   Reviewed by eLife

3. All-trans retinoic acid induces synaptic plasticity in human cortical neurons

   This article has 7 authors:

   1. Maximilian Lenz
   2. Pia Kruse
   3. Amelie Eichler
   4. Jakob Straehle
   5. Jürgen Beck
   6. Thomas Deller
   7. Andreas Vlachos

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: All three reviewers are highly enthusiastic about the study reporting the acute effects of retinoic acid on excitatory synaptic transmission and its underlying mechanisms. The experiments are well executed and the results convincing. Aside from some minor comments that require minimal additional experiments or further clarification, the reviewers expressed one major concern regarding the dentate gyrus LTP data. Although further experiments are required to clarify the concerns, the reviewers recommended removing the LTP figure from the present study as it is not well connected with the rest of the study.

   Reviewed by eLife

4. Analysis of ultrasonic vocalizations from mice using computer vision and machine learning

   This article has 5 authors:

   1. Antonio HO Fonseca
   2. Gustavo M Santana
   3. Gabriela M Bosque Ortiz
   4. Sérgio Bampi
   5. Marcelo O Dietrich

   Reviewed by eLife

5. Beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne muscular dystrophy

   This article has 15 authors:

   1. Elisabeth A Kilroy
   2. Amanda C Ignacz
   3. Kaylee L Brann
   4. Claire E Schaffer
   5. Devon Varney
   6. Sarah S Alrowaished
   7. Kodey J Silknitter
   8. Jordan N Miner
   9. Ahmed Almaghasilah
   10. Tashawna L Spellen
   11. Alexandra D Lewis
   12. Karissa Tilbury
   13. Benjamin L King
   14. Joshua B Kelley
   15. Clarissa A Henry

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: The authors seek to tackle the question of exercise and inactivity in Duchenne muscular dystrophy, an important and unsolved issue. They use the zebrafish model system and two paradigms, one an inactivity paradigm (using tricaine) and the other an exercise paradigm using NMES. They find that inactivity worsens the dystrophic phenotype, and that different exercise paradigms impact the dystrophic phenotype differently. Overall this is an important study with exciting data and a potential to impact our understanding of exercise in DMD. However, as described below, all reviewers felt that several critical experimental considerations are necessary to consider in order to substantiate the data claims.

   Reviewed by eLife

6. Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

   This article has 11 authors:

   1. Gang Wu
   2. Yin Yeng Lee
   3. Evelyn M Gulla
   4. Andrew Potter
   5. Joseph Kitzmiller
   6. Marc D Ruben
   7. Nathan Salomonis
   8. Jeffery A Whitsett
   9. Lauren J Francey
   10. John B Hogenesch
   11. David F Smith

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: Obstructive sleep apnea is an important medical problem, with elevated cardiovascular risk as a common association. Intermittent hypoxic episodes are a good predictor of such risk so a connection is indeed plausible. The authors use single cell genomics to delineate the changes in intermittent hypoxia models, with interesting insights, but what limits enthusiasm is validation of some hypothesis generating findings from single cell data, limiting potential mechanistic insights that are translatable to OSA.

   Reviewed by eLife

7. ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

   This article has 14 authors:

   1. Jormay Lim
   2. Hsiao-Hsin Tai
   3. Wei-Hao Liao
   4. Ya-Cherng Chu
   5. Chen-Ming Hao
   6. Yueh-Chun Huang
   7. Cheng-Han Lee
   8. Shao-Shien Lin
   9. Sherry Hsu
   10. Ya-Chih Chien
   11. Dar-Ming Lai
   12. Wen-Shiang Chen
   13. Chih-Cheng Chen
   14. Jaw-Lin Wang

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: This is an interesting manuscript suggesting that ultrasound stimuli induce movements of the extracellular matrix and the cytoskeleton to cause mechanical activation of ASIC1a in cortical neurons. This is a novel finding.

   Reviewed by eLife

8. A multifaceted analysis reveals two distinct phases of chloroplast biogenesis during de-etiolation in Arabidopsis

   This article has 10 authors:

   1. Rosa Pipitone
   2. Simona Eicke
   3. Barbara Pfister
   4. Gaetan Glauser
   5. Denis Falconet
   6. Clarisse Uwizeye
   7. Thibaut Pralon
   8. Samuel C Zeeman
   9. Felix Kessler
   10. Emilie Demarsy

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: All three reviewers as well as myself are impressed by the in depth and multi-method analysis of chloroplast and thylakoid membrane development provided in your study, including time courses of 3D imaging combining TEM, SBF-SEM and confocal microscopy, lipidomics and proteomics. However, some analyses need to be improved and/or better explained.

     • There is a concern about the proteomics analysis, as the low number of proteins changing in abundance upon de-etiolation is unexpected. It is not clear how the samples were harvested. Were they harvested in the light and could that have influenced protein abundance? The harvesting procedure needs to be better explained. Or is the proteomics method not sensitive enough? The proteomics should be validated, for example by Western Blots with well-established marker proteins such as phyA and HY5.

     • Please also add loading controls to Fig 6 and the associated supplemental figure.

     • Please explain better how the volume of dividing chloroplasts was determined.

   Reviewed by eLife

9. A novel role for the lateral habenula in fear learning

   This article has 7 authors:

   1. Tomas E. Sachella
   2. Marina R. Ihidoype
   3. Christophe D. Proulx
   4. Diego E. Pafundo
   5. Jorge H. Medina
   6. Pablo Mendez
   7. Joaquin Piriz

   This article has been curated by 1 group:

   • Curated by eLife

     Summary: The manuscript examined the role of the lateral habenula (LHb) on contextual and cued fear conditioning with tests occurring at different time points since acquisition. The investigation provided important controls and systematic examination of testing and training conditions in places. The findings are interesting and likely of broad significance. However, the reviewers felt that the investigation lacked focus; that is, a more hypothesis-driven examination of the potential role of the LHb in the differential disruption of contextual and cued fear was viewed as necessary to make a major impact on a broad range of readers. Currently, there is not a clear and strong interpretation of the data, and more studies are necessary to further explore some of the options put forward by the authors.

   Reviewed by eLife

10. Fibre-specific laterality of white matter in left and right language dominant people

    This article has 4 authors:

    1. Helena Verhelst
    2. Thijs Dhollander
    3. Robin Gerrits
    4. Guy Vingerhoets

    This article has been curated by 1 group:

    • Curated by eLife

      Summary: The paper tackles an important aspect of neuroanatomical and language research concerning the lateralization differences related to functional lateralization of language. No clear cut results are currently available nowadays and methodological limitations of previous approaches are here addressed with a new angle in the tractography analysis. This is certainly of interest, the methodology is sound and the results deserve to be published. However, as you will see all the reviews highlighted that the novelty of this work both in terms of the methodology and results is somewhat limited, in addition to concerns about the nature of the task used. This makes it seem better suited to a more specialized readership.

    Reviewed by eLife