eLife

Latest preprint reviews

1. Neural synchronization is strongest to the spectral flux of slow music and depends on familiarity and beat salience

   This article has 3 authors:

   1. Kristin Weineck
   2. Olivia Xin Wen
   3. Molly J Henry

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study investigated the neural tracking of music using novel methodology. The core finding was stronger neuronal entrainment to "spectral flux" than to other, more commonly tested features such as amplitude envelope. As such the study is methodologically sophisticated and provides novel insight on the neuronal mechanisms of music perception.

     (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

2. Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis

   This article has 8 authors:

   1. Nathaniel R Braffman
   2. Terry B Ruskoski
   3. Katherine M Davis
   4. Nathaniel R Glasser
   5. Cassidy Johnson
   6. C Denise Okafor
   7. Amie K Boal
   8. Emily P Balskus

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The de novo crystal structure of the cyanobacterial enzyme CylK, which assembles cylindrocyclophane natural products, is reported. The substrate-binding site and critical catalytic residues were identified through a combination of anion soaking, mutagenesis, molecular dynamic simulations. The insights from this work are relevant in understanding biological Friedel-Crafts alkylation and also in enzyme engineering and catalyst designs. This is a very comprehensive study that provides new mechanistic insights for this enzyme and it will be of interest to all who are involved in enzyme engineering, catalyst design, and natural product discovery.

     (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. Interactions between strains govern the eco-evolutionary dynamics of microbial communities

   This article has 5 authors:

   1. Akshit Goyal
   2. Leonora S Bittleston
   3. Gabriel E Leventhal
   4. Lu Lu
   5. Otto X Cordero

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors attempt to derive a threshold of genetic distance, beyond which two microbial strains diverge in their behavior in an ecological community. The question is of broad interest to ecology, especially microbial ecology. To answer this question, the authors followed the population dynamics of individual strains derived from a natural microbial community under constant environmental conditions in the lab. The statistical framework could be improved, and a more rigorous account of how the phylogenetic inference of strains and species was made should be given.

     (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. TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

   This article has 13 authors:

   1. Amit Jairaman
   2. Amanda McQuade
   3. Alberto Granzotto
   4. You Jung Kang
   5. Jean Paul Chadarevian
   6. Sunil Gandhi
   7. Ian Parker
   8. Ian Smith
   9. Hansang Cho
   10. Stefano L Sensi
   11. Shivashankar Othy
   12. Mathew Blurton-Jones
   13. Michael D Cahalan

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Microglia are a key cell type in the brain that clear debris following tissue injury, infections, or in neurodegenerative diseases. This role is influenced strongly by directed migration of microglia towards the regions of brain injury or infection. TREM2 is a myeloid protein expressed in microglia that has been linked to Alzheimer's Disease, but the mechanisms of how TREM2 loss-of-function mutations affect microglial function is unclear. Here, Jairaman and colleagues address this question using CRISPR-based knockout of TREM2 in human iPSC-derived microglia. The study finds that TREM2 KO microglia have greatly exaggerated ADP/ATP evoked Ca signals, which is found to arise from increases in P2Y12 and P2Y13 receptor expression and enhanced receptor-evoked Ca signaling. TREM2 KO microglia show alterations in cell migration, which include, on the one hand, increased cell motility, but also reduced turning, and importantly, markedly reduced directed migration. The experiments and analysis are carefully performed using appropriate controls and the results are novel and add to our understanding of how loss-of-function TREM2 mutations impact microglial migration and the ensuing microglia-mediated clearance of plaques and damage seen in AD. Several weaknesses cloud the interpretation, but if appropriately addressed, this could be an important paper for the field.

     (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. Self-organization of in vitro neuronal assemblies drives to complex network topology

   This article has 6 authors:

   1. Priscila C Antonello
   2. Thomas F Varley
   3. John Beggs
   4. Marimélia Porcionatto
   5. Olaf Sporns
   6. Jean Faber

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript is of interest to readers working on neuronal network dynamics and development. It uses an in vitro model to characterize the emergence of complex topology in neuronal circuits. The presented mathematical tools for data analysis are sophisticated and supported by numerical simulations. However, further investigation is required to delineate the specific mechanisms of network formation.

     (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. Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation

   This article has 13 authors:

   1. Francesco M Piccolo
   2. Nathaniel R Kastan
   3. Tomomi Haremaki
   4. Qingyun Tian
   5. Tiago L Laundos
   6. Riccardo De Santis
   7. Andrew J Beaudoin
   8. Thomas S Carroll
   9. Ji-Dung Luo
   10. Ksenia Gnedeva
   11. Fred Etoc
   12. AJ Hudspeth
   13. Ali H Brivanlou

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript harnesses an organoid model of human neurulation to unravel the role of the Hippo signalling pathway in the specification of the three key ectodermal cell types. The authors then investigate how these mechanisms are dysregulated in an organoid model of Huntington’s disease. The overall conclusions of this work are mostly supported by the data, though the implications of the regulatory relationships studied here to Huntington's Disease in adults would need further elucidation. With some clarifications of data acquisition and experimental logic, this work will be of broad interest to readers interested in the process of neurulation and how dysregulation of developmental mechanisms may lead to disease conditions in adulthood.

     (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. Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

   This article has 7 authors:

   1. Ambuj Upadhyay
   2. Nathan R Feltman
   3. Adam Sychla
   4. Anna Janzen
   5. Siba R Das
   6. Maciej Maselko
   7. Michael Smanski

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper is of interest to entomologists caring for genetic pest control or molecular biologists following synthetic biology. The authors describe a fruit fly strain that combines constructs that establish both repressible female-lethality and genetic incompatibility based on CRISPR transactivation. They show that this strain has high penetrance for these two traits and that it can suppress wild-type flies when released into cycling cage populations. The paper is thus a neat technology demonstration for a genetic control strategy possibly applicable to other insects including pests or disease vectors.

     (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

8. LRET-derived HADDOCK structural models describe the conformational heterogeneity required for DNA cleavage by the Mre11-Rad50 DNA damage repair complex

   This article has 2 authors:

   1. Marella D Canny
   2. Michael P Latham

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study on the Mre11 and Rad50 proteins is of interest to biologists studying DNA repair. Advances in the understanding of Mre11-Rad50 mechanism, for instance how structural states are linked to DNA end detection and DNA processing as addressed in this study, are of central importance to research on genome stability and DNA repair, with implications in human disease such as cancer and immune disorders. Enzymatically, RAD50 is an ATPase and MRE11 is a nuclease with both exo- and endo-nuclease activities. How all these functions are catalyzed by the complex remains unresolved. This study identifies three conformations of ATP-bound P. furiosus Mre11-Rad50 complex: open, partially open, and closed. The work would benefit from further experiments to clarify the functional difference between the partially open and open conformations.

     (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. Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans

   This article has 7 authors:

   1. Kelsie RS Doering
   2. Xuanjin Cheng
   3. Luke Milburn
   4. Ramesh Ratnappan
   5. Arjumand Ghazi
   6. Dana L Miller
   7. Stefan Taubert

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study brings new insight into how organisms maintain homeostasis under stress conditions and has implications for our understanding both development and disease. The study provides evidence that NHR-49 protects animals from hypoxia by activating autophagy, and that it acts independently of the well-described canonical HIF-1 hypoxia response. The experiments are well done, and the conclusions from the results are largely appropriate. The impact of this study will be highest in the specific field of hypoxia, with more moderate impact for wider audiences interested in understanding of how biological maintain homeostasis under stress.

     (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. Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader

    This article has 7 authors:

    1. Christl Gaubitz
    2. Xingchen Liu
    3. Joshua Pajak
    4. Nicholas P Stone
    5. Janelle A Hayes
    6. Gabriel Demo
    7. Brian A Kelch

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This work reports several cryoEM structures of clamp loader-sliding clamp complexes, which are required for DNA replication and repair in all domains of life, and is of interest to researchers studying DNA metabolism and motor proteins. The findings provide new insight into the mechanism of clamp loading and the mechanisms by which ligands affect the conformational dynamics of motor proteins to facilitate their reactions.

      (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