eLife

Latest preprint reviews

1. Analyzing the brainstem circuits for respiratory chemosensitivity in freely moving mice

   This article has 6 authors:

   1. Amol Bhandare
   2. Joseph van de Wiel
   3. Reno Roberts
   4. Ingke Braren
   5. Robert Huckstepp
   6. Nicholas Dale

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study utilizes a miniscope approach and GCaMP6 in freely behaving conscious mice to record CO2-associated multicellular calcium responses of neurons or glia in brainstem regions implicated in CO2-dependent control of breathing. The application of this approach in this context is extremely attractive, and new to the respiratory neurobiology field. Several technical improvements could strengthen the manuscript. Foremost, the study is broad in scope and consequently not always technically rigorous in important aspects such as identification of cell types imaged. In some cases that affects interpretation of the significance of the results. Since some of the conclusions about cellular responses to CO2 are mostly at odds with a substantial literature using more established techniques, there is even greater onus on the authors to ensure reliability of the results.

     (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

2. Crystal structures of bacterial small multidrug resistance transporter EmrE in complex with structurally diverse substrates

   This article has 6 authors:

   1. Ali A Kermani
   2. Olive E Burata
   3. B Ben Koff
   4. Akiko Koide
   5. Shohei Koide
   6. Randy B Stockbridge

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     E. coli EmrE and other members of the SMR family of transporters utilize the proton motive force to pump out a broad spectrum of antibiotics, thereby contributing to multi-drug resistance. Here, a new multipurpose crystallization chaperone is used to determine the structure of EmrE in apo form and in complex with various substrates. The strength of the manuscript is in the description of six new structures of EmrE at a resolution sufficient for building an atomic model and understanding how the antimicrobial agents bind, allowing robust conclusions to be drawn regarding the molecular details of binding of the antimicrobial agents. The report will be of interest to both those studying antibiotic resistance and those studying transporters.

     (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

3. Modeling the consequences of the dikaryotic life cycle of mushroom-forming fungi on genomic conflict

   This article has 3 authors:

   1. Benjamin Auxier
   2. Tamás L Czárán
   3. Duur K Aanen

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Unions between equal partners can be destabilized by matings with third parties. In this paper the authors demonstrated that in fungi, 'stable unions' of two nuclei (dikaryons) are predicted to experience costs to vegetative fitness from investment in such mating opportunities. 'Open unions', in which third parties have access to the resources of established partnerships, are evolutionarily highly unstable. This paper will be of general interest to those who study evolutionary conflicts and to fungal geneticists.

     (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 name with the authors.)

   Reviewed by eLife

4. Machine learning sequence prioritization for cell type-specific enhancer design

   This article has 18 authors:

   1. Alyssa J Lawler
   2. Easwaran Ramamurthy
   3. Ashley R Brown
   4. Naomi Shin
   5. Yeonju Kim
   6. Noelle Toong
   7. Irene M Kaplow
   8. Morgan Wirthlin
   9. Xiaoyu Zhang
   10. BaDoi N Phan
   11. Grant A Fox
   12. Kirsten Wade
   13. Jing He
   14. Bilge Esin Ozturk
   15. Leah C Byrne
   16. William R Stauffer
   17. Kenneth N Fish
   18. Andreas R Pfenning

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript describes an exciting new approach for tagging and isolation of unique neuronal subpopulations, which has traditionally been challenging without the incorporation of expensive and time consuming transgenic animal colonies. While the manuscript highlights a specific test case of this technology with neurons expressing Parvalbumin, in theory this method could be applied to any neuronal or even non-neuronal cell type. Further, this approach could be applied to other model organisms for which transgenic technologies are limited, thereby facilitating research in other species.

     (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 #3 agreed to share their names with the authors.)

   Reviewed by eLife

5. Speed variations of bacterial replisomes

   This article has 5 authors:

   1. Deepak Bhat
   2. Samuel Hauf
   3. Charles Plessy
   4. Yohei Yokobayashi
   5. Simone Pigolotti

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript uses experiments and theory to characterize the variations in replication speed of E.coli throughout cell cycle. The authors developed a theory to account for fluctuations in the replication velocity as well as a cell-cycle-dependent speed, and by using sequencing data they analyzed the variations in the speed for E. coli. They found that replication speed increases with increasing temperature, and also observed oscillatory patterns in the speed of the replisome, consistent with variations in mutation rate (accuracy) across the genome. These observations suggest a tradeoff between replication speed and accuracy in E.coli.

     (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

6. Measuring the tolerance of the genetic code to altered codon size

   This article has 3 authors:

   1. Erika Alden DeBenedictis
   2. Dieter Söll
   3. Kevin M Esvelt

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Using a phage-based library generation and selection, the authors generated a suite of 4-base decoding tRNAs with improved efficiency in quadruplet decoding. The data represent an important step toward enhancing protein synthesis with 4-base codons. Overall, the approach to generate many tRNA variants with quadruplet anticodons is intriguing and provides a wealth of valuable information to the field. The results, once some of the reviewer concerns have been addressed, should become foundational for the field of synthetic biology.

     (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

7. Endogenous Syngap1 alpha splice forms promote cognitive function and seizure protection

   This article has 17 authors:

   1. Murat Kilinc
   2. Vineet Arora
   3. Thomas K Creson
   4. Camilo Rojas
   5. Aliza A Le
   6. Julie Lauterborn
   7. Brent Wilkinson
   8. Nicolas Hartel
   9. Nicholas Graham
   10. Adrian Reich
   11. Gemma Gou
   12. Yoichi Araki
   13. Àlex Bayés
   14. Marcelo Coba
   15. Gary Lynch
   16. Courtney A Miller
   17. Gavin Rumbaugh

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Given the well-known importance of the SYNGAP1 mutations in the pathophysiology of neurodevelopmental disorders and the key regulatory roles of SynGAP1 for excitatory synaptic functions, this study provides timely and comprehensive sets of data supporting the in vivo functions of individual SynGAP1 splice variants, including the alpha-1/2 variants, and suggests the therapeutic potential of increasing specific SynGAP1-alpha variants.

     (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. Determination of oligomeric states of proteins via dual-color colocalization with single molecule localization microscopy

   This article has 5 authors:

   1. Hua Leonhard Tan
   2. Stefanie Bungert-Plümke
   3. Daniel Kortzak
   4. Christoph Fahlke
   5. Gabriel Stölting

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors present a method for measuring the oligomerisation state of tagged membrane proteins by PALM co-localisation that is new, interesting and potentially very useful for identifying oligomerization states of unknown proteins in native cells. While the authors develop a basic theory and apply the method to a set of candidate proteins with solid results, their implementation could be refined and improved, which would help to better delineate the full scope and the limitations of their method. An open-source software tool would help other researchers to adopt this analysis. The work is relevant for cell biologists, especially those studying membrane proteins.

     (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. Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity

   This article has 9 authors:

   1. Yunseok Heo
   2. Eojin Yoon
   3. Ye-Eun Jeon
   4. Ji-Hye Yun
   5. Naito Ishimoto
   6. Hyeonuk Woo
   7. Sam-Yong Park
   8. Ji-Joon Song
   9. Weontae Lee

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript reports the cryoEM structure of somatostatin receptor 2 (SSTR2) bound to its agonist SST-14 and a heterotrimeric G protein. In addition to presenting the structure itself, the authors include discussion and analysis of ligand recognition and subtype specificity, guided by AlphaFold2 modeling of other somatostatin receptor subtypes. Additional functional data to test the importance of proposed receptor-ligand contacts will be critical to understanding which of the features directly contribute to subtype specificity. Because somatostatin signaling is important in endocrine biology, including in diseases such as acromegaly and some cancers, the work should in principle be of interest to a broad audience.

     (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

10. Determinants of trafficking, conduction, and disease within a K+ channel revealed through multiparametric deep mutational scanning

    This article has 4 authors:

    1. Willow Coyote-Maestas
    2. David Nedrud
    3. Yungui He
    4. Daniel Schmidt

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This is a tour de force for mutagenesis and analysis of an ion channel protein, using a straightforward method the authors have developed for the comprehensive functional analysis of a deep mutational library. The approach introduced here will not only be of broad interest to the ion channel community, but it will also serve as a roadmap for performing similar studies on other proteins. The authors demonstrate the usefulness of this method by defining the functional domains of Kir2.1, thereby rediscovering known disease causing mutants, and highlighting a number of mutations with similar phenotypes that may also result in disease phenotypes.

      (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 and Reviewer #3 agreed to share their name with the authors.)

    Reviewed by eLife