eLife

Latest preprint reviews

1. Differential ion dehydration energetics explains selectivity in the non-canonical lysosomal K+ channel TMEM175

   This article has 8 authors:

   1. SeCheol Oh
   2. Fabrizio Marinelli
   3. Wenchang Zhou
   4. Jooyeon Lee
   5. Ho Jeong Choi
   6. Min Kim
   7. José D Faraldo-Gómez
   8. Richard K Hite

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript explores the mechanisms of permeation and selectivity in the unusual potassium-selective ion channel TMEM175, which lacks a canonical selectivity filter. The study is led by molecular dynamics simulations and free energy calculations, complemented by a cryoEM analysis and electrophysiological recordings. The authors propose a novel, single ion-based mechanism of permeation, together with a partial dehydration-driven selectivity mechanism. While in principle exciting and informative, most of the conclusions in the manuscript are based on small differences in calculated values for which an estimation of the uncertainty is lacking, and on the usage of a single physics-based model. This study will appeal to readers interested in the structure and function of ion channels and in molecular mechanisms of ion translocation. It would be strengthened by a thorough exploration of alternative hypotheses.

     (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

2. Contextual effects in sensorimotor adaptation adhere to associative learning rules

   This article has 5 authors:

   1. Guy Avraham
   2. Jordan A Taylor
   3. Assaf Breska
   4. Richard B Ivry
   5. Samuel D McDougle

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper is of interest to scientists within the field of motor control and learning. The experiments provide novel insight into the potential role of associative learning in sensorimotor adaptation. The results are compelling, although further data are required to support several key conclusions.

     (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. Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells

   This article has 7 authors:

   1. Kei Fukuda
   2. Yoshinori Makino
   3. Satoru Kaneko
   4. Chikako Shimura
   5. Yuki Okada
   6. Kenji Ichiyanagi
   7. Yoichi Shinkai

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The majority, but not all retrotransposons undergo massive reprogramming of their methylation states during germ cell development. This manuscript tests the contribution of binding motifs for KRAB-Zinc Finger Proteins (KZFPs) and the position of retrotransposons relative to genes to explain the variable methylation dynamics of different retrotransposon families, namely L1, SVA and LTR12, as well as potential inter-individual variation during male germ cell development in humans, using an integrative analyses of available sequencing datasets. By bringing insights into the complex regulation of retrotransposons, this study could be of particular interest to the epigenetics community. Some additional analyses would strengthen the inferences made.

     (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. Doublecortin engages the microtubule lattice through a cooperative binding mode involving its C-terminal domain

   This article has 9 authors:

   1. Atefeh Rafiei
   2. Sofía Cruz Tetlalmatzi
   3. Claire H Edrington
   4. Linda Lee
   5. D Alex Crowder
   6. Daniel J Saltzberg
   7. Andrej Sali
   8. Gary Brouhard
   9. David C Schriemer

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Rafiei et al. investigate the molecular architecture of an important neuronal microtubule-associated protein, doublecortin, bound to the microtubule by integrating data from chemical cross-linking experiments with available crystallographic and cryo-EM structures. They present an appealing model of microtubule-mediated self-association of doublecortin; however, they do not perform any additional assays to support the functional relevance of this model. In addition, there are limitations to the used method in resolving structural details. The manuscript will be relevant for biologists with an interest in microtubule formation and to researchers who apply different structural biology tools to study the organization of large biomolecular assemblies.

     (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 names with the authors.)

   Reviewed by eLife

5. Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA

   This article has 6 authors:

   1. Marta Matuszewska
   2. Gemma GR Murray
   3. Xiaoliang Ba
   4. Rhiannon Wood
   5. Mark A Holmes
   6. Lucy A Weinert

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Understanding where new strains of microbes come from and how they change over time is important for infection control and prevention. Staphylococcus aureus CC398 is an important strain that 'spills over' from livestock to humans, carrying with it high levels of resistance to antibiotics commonly used in farming. This paper compares more than 1000 genomes of CC398 and concludes that spillover is likely to carry resistance to tetracyclines and other antibiotics into humans that will persist over time.

     (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. Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells

   This article has 8 authors:

   1. Sarah Lensch
   2. Michael H Herschl
   3. Connor H Ludwig
   4. Joydeb Sinha
   5. Michaela M Hinks
   6. Adi Mukund
   7. Taihei Fujimori
   8. Lacramioara Bintu

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study describes a novel approach to investigate how the transcriptional repressors KRAB and HDAC4 repress gene expression, how repression spreads over differing genomic distances, and what the role of insulator elements is in blocking the spread of repression and in reactivation of repressed genes. The results of this study allow modeling of the coordinated repression or activation of closely linked genes and should be of wide interest to researchers interested in chromatin and gene expression.

     (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. Reconstitution of surface lipoprotein translocation through the Slam translocon

   This article has 6 authors:

   1. Minh Sang Huynh
   2. Yogesh Hooda
   3. Yuzi Raina Li
   4. Maciej Jagielnicki
   5. Christine Chieh-Lin Lai
   6. Trevor F Moraes

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This work provides new insights into how surface-exposed lipoproteins of Gram-negative bacteria reach their destination in the outer membrane. Authors find that the outer membrane protein complex Slam serves as a translocon for the lipoproteins and the periplasmic chaperone Skp mediates their targeting to Slam. This work may contribute to the elucidation of host invasion mechanisms by pathogenic bacteria, in which surface lipoproteins play an important role.

     (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. Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells

   This article has 6 authors:

   1. Andrew T Landau
   2. Pojeong Park
   3. J David Wong-Campos
   4. He Tian
   5. Adam E Cohen
   6. Bernardo L Sabatini

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Synaptic plasticity typically requires the conjunction of dendritic action potentials and synaptic activation. Together these signals cause nonlinear changes in calcium influx that then drive plasticity. The strength of these interactions can vary in complex ways. The authors use an elegant combination of imaging and electrophysiology to convincingly show how some of these complexities in murine cortical neurons arise from electrical properties of neuronal dendrites and synaptic NMDA receptors. This is a thorough and well done analysis of a set of issues that have implications for the ways in which dendritic morphology affect plasticity "rules." The underlying principles are largely previously understood, but their implications (e.g. the difference between voltage dependence of calcium channel and NMDA receptor calcium influx) are not widely appreciated and yet have important effects on the resulting integration.

     (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. DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes

   This article has 7 authors:

   1. Anne C Meinema
   2. Anna Marzelliusardottir
   3. Mihailo Mirkovic
   4. Théo Aspert
   5. Sung Sik Lee
   6. Gilles Charvin
   7. Yves Barral

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This interesting study examines a potential relationship between the tethering of extrachromosomal DNA (ecDNA) to the nuclear pore complex (NPC) and its role in aging; a model is proposed whereby the nuclear basket is displaced by ecDNA anchoring, which leads to a broader remodeling of the NPC that is distinct from NPC damage. This idea is conceptually novel and will represent an important advance, although some more support for the conclusions is still needed.

     (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

10. The human FLT1 regulatory element directs vascular expression and modulates angiogenesis pathways in vitro and in vivo

    This article has 15 authors:

    1. Julian Stolper
    2. Holly K. Voges
    3. Michael See
    4. Neda Rahmani Mehdiabadi
    5. Gulrez Chahal
    6. Mark Drvodelic
    7. Michael Eichenlaub
    8. Tanya Labonne
    9. Benjamin G. Schultz
    10. Alejandro Hidalgo
    11. Lazaro Centanin
    12. Jochen Wittbrodt
    13. Enzo R. Porrello
    14. David A. Elliott
    15. Mirana Ramialison

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This paper aims to identify enhancers controlling human cardiovascular development. The authors identified a set of highly conserved regulatory elements bioinformatically and tested one of these in vivo, in medaka, and in vitro, in hESC differentiated into endothelial cells. They find deletion of this enhancer had no significant effect on the expression of FLT1 mRNA in the human cell line or on the formation of tube formation. However, deletion of the orthologous enhancer in medaka showed phenotypic effects in blood clot formation. Together, the data provide insights into the function of an enhancer controlling FLT1. This manuscript will be of interest to scientists interested in gene regulation, vascular biology and developmental 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