eLife

Latest preprint reviews

1. De novo-designed transmembrane domains tune engineered receptor functions

   This article has 11 authors:

   1. Assaf Elazar
   2. Nicholas J Chandler
   3. Ashleigh S Davey
   4. Jonathan Y Weinstein
   5. Julie V Nguyen
   6. Raphael Trenker
   7. Ryan S Cross
   8. Misty R Jenkins
   9. Melissa J Call
   10. Matthew E Call
   11. Sarel J Fleishman

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This is an interesting paper that uses de novo protein design to probe the effects of oligomerization state on the activity of chimeric antigen receptors (CARS). The successful design of transmembrane domains with specific oligomeric states is an impressive result on its own. The proteins were designed using rotamer-based sequence optimization in Rosetta with an energy function specific for the membrane environment. After experimentally evaluating a couple rounds of designs, the investigators settled on a design protocol that also included screening of the design candidates with docking simulations in alternative oligomerization states to check that the sequences preferred the desired oligomerization state. The designs were experimentally evaluated with gel electrophoresis and X-ray crystallography. In the end, designs that adopted well-defined dimers, trimers, or tetramers were created and carried forward in experiments as CARs.

     (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 name with the authors.)

   Reviewed by eLife

2. Dnmt3a knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3

   This article has 18 authors:

   1. Junhao Li
   2. Antonio Pinto-Duarte
   3. Mark Zander
   4. Michael S Cuoco
   5. Chi-Yu Lai
   6. Julia Osteen
   7. Linjing Fang
   8. Chongyuan Luo
   9. Jacinta D Lucero
   10. Rosa Gomez-Castanon
   11. Joseph R Nery
   12. Isai Silva-Garcia
   13. Yan Pang
   14. Terrence J Sejnowski
   15. Susan B Powell
   16. Joseph R Ecker
   17. Eran A Mukamel
   18. M Margarita Behrens

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this manuscript the authors conditionally knock out the DNA methyltransferase Dnmt3a in developing excitatory cortical neurons to determine the consequences for chromatin regulation, gene expression, and neuron function. As expected they find widespread loss of DNA methylation at CpA dinucleotides but also an increase in histone methylation (H3K27me3) at many similar regions of the genome, which they speculate may be a mechanism of functional compensation. Overall this study offers new insights into the gene regulatory and neuronal cellular functions of an important chromatin regulatory protein.

     (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

3. Distinct representation of cue-outcome association by D1 and D2 neurons in the ventral striatum’s olfactory tubercle

   This article has 4 authors:

   1. Nuné Martiros
   2. Vikrant Kapoor
   3. Spencer E Kim
   4. Venkatesh N Murthy

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this manuscript the authors carefully describe the activity of individual neurons within the mouse olfactory tubercle, comprised of the two principal cell types, in the context of odor and tone associative learning. The use of 2-photon microscopy to monitor activity of the neurons is a major step forward and unveiled new insights into the dynamics of these neurons. This manuscript will be of interest to a wide range of readers, including those interested in affective circuits, learning, and sensory processing.

     (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. A neural network model of hippocampal contributions to category learning

   This article has 2 authors:

   1. Jelena Sučević
   2. Anna C Schapiro

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper will be of broad interest to researchers interested in learning, memory, and/or the hippocampus. It offers a neuroanatomically inspired model of the hippocampus that reconciles its well-known role in episodic memory with its more recently appreciated role in category learning and generalization. The computational simulations are well conducted and support the key conclusions regarding complementary roles of distinct hippocampal pathways for different forms of learning. There are concerns with differentiating the current work from prior reports and the apparent discrepancy between the proposed model and well-established findings of place and concept cell recordings in hippocampus, but thought that these issues could be potentially resolved with additional clarification.

     (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

5. Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022

   This article has 7 authors:

   1. Wha-Eum Lee
   2. Sang Woo Park
   3. Daniel M Weinberger
   4. Donald Olson
   5. Lone Simonsen
   6. Bryan T Grenfell
   7. Cécile Viboud

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors examine the impacts of the COVID-19 pandemic on excess mortality in the US up to April 30, 2021. The authors separate direct impacts (caused by COVID-19, coded as such or not) of the pandemic from indirect impacts (disruptions), finding that most excess deaths (90%) are due to direct impacts. Importantly, the authors find that the official COVID-19 death tally is an undercount of these deaths. Moreover, the authors also find that excess deaths due to other causes are the main driver of excess mortality among younger populations. The paper is interesting and well written, although we have some concerns, particularly around the estimation of direct vs. indirect impacts.

     (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, ScreenIT

6. Solute exchange through gap junctions lessens the adverse effects of inactivating mutations in metabolite-handling genes

   This article has 9 authors:

   1. Stefania Monterisi
   2. Johanna Michl
   3. Alzbeta Hulikova
   4. Jana Koth
   5. Esther M Bridges
   6. Amaryllis E Hill
   7. Gulnar Abdullayeva
   8. Walter F Bodmer
   9. Pawel Swietach

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This work shows that spontaneous mutations in cancer cells affecting metabolic pathways do not necessarily result in functional defects, as affected cells may be able to be rescued by gap junction-mediated exchange of metabolites. This is verified in three specific examples, although some of the "quantitative" methods of measuring gap junctional coupling are actually only qualitative in nature. In addition, more experiments are needed to address the effect of Cx31 and Cx43 KD. This paper is of potential interest to a broad readership in cancer biology as well as colleagues studying metabolic pathways.

     (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. Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human

   This article has 9 authors:

   1. Petra Wahle
   2. Eric Sobierajski
   3. Ina Gasterstädt
   4. Nadja Lehmann
   5. Susanna Weber
   6. Joachim HR Lübke
   7. Maren Engelhardt
   8. Claudia Distler
   9. Gundela Meyer

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Wahle and colleagues investigate the pervasiveness of the non-canonical arrangement of axons emerging from dendrites rather than the soma of neocortical pyramidal cells of different mammalian species. Using a variety of anatomical techniques, the authors demonstrate that axons can originate directly from pyramidal cell dendrites in species as diverse as rodents, ferret, cats, pigs and primates. Cross-species comparisons indicate that non-primate brains have a higher proportion of axon-carrying-dendrites (AcD) than did brains of macaques or humans. This paper is of potential interest to a broad range of neuroscientists in reporting the distribution of this non-canonical structure and indicating that primate brains may potentially feature axons emanating from dendrites less commonly.

     (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

8. Role of oxidation of excitation-contraction coupling machinery in age-dependent loss of muscle function in Caenorhabditis elegans

   This article has 7 authors:

   1. Haikel Dridi
   2. Frances Forrester
   3. Alisa Umanskaya
   4. Wenjun Xie
   5. Steven Reiken
   6. Alain Lacampagne
   7. Andrew Marks

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript will appeal to all with an interest in comparative physiology and the molecular biology of age-associated changes in muscle function. The authors draw parallels between aging skeletal muscle in humans and C. elegans, with evidence in support of age-dependent oxidation of the C. elegans ryanodine receptor ortholog, UNC-68, causing loss of the calstabin ortholog, FKB-2. This in turn results in UNC-68 "leakiness", reduced body wall Ca2+ transients and muscle weakness-changes in ryanodine receptor complex structure and function, changes that are similar to those that occur in aging human skeletal muscle despite the dramatic differences in the lifespan of the two organisms. The experimental approaches are generally sound, although the intriguing dataset that is open to multiple interpretations.

     (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. Relative role of border restrictions, case finding and contact tracing in controlling SARS-CoV-2 in the presence of undetected transmission

   This article has 4 authors:

   1. Rachael Pung
   2. Hannah E. Clapham
   3. Vernon J. Lee
   4. Adam J Kucharski

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper will be of interest to infectious disease epidemiologists and modellers working on situational assessment, and public health researchers focused on COVID19 response. Through an informative case study on the Singaporean COVID19 epidemic, the paper provides estimates of case ascertainment under different levels of border restrictions and public health measures, as well as estimates of the effectiveness of contact tracing in reducing transmission. The combination of data from multiple sources with mathematical modeling provides a powerful tool to assess effectiveness of interventions. Some of the key claims of the manuscript - while plausible - are not directly supported by the analyses, and the methods and modelling assumptions require more detailed exposition.

     (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 name with the authors.)

   Reviewed by eLife, ScreenIT

10. Single-cell transcriptomics of a dynamic cell behavior in murine airways

    This article has 5 authors:

    1. Sheldon JJ Kwok
    2. Daniel T Montoro
    3. Adam L Haber
    4. Seok-Hyun Yun
    5. Vladimir Vinarsky

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This is an interesting manuscript presenting an ex vivo explant model that allows combining live cell imaging with single-cell transcriptomic analyses. Using mouse models with specific fluorescent reporters that can be used to characterize cellular behaviour in the transplanted tissue and mark individual cells, the authors show that this approach can be used to identify transcriptional differences between cells that differ in cellular movement features during epithelial repair after injury. This is a first step to further expanding the description of cellular heterogeneity, including cellular behavioural as well as transcriptomic features. This manuscript is of broad interest to cell biologists as it describes a new method that links cellular behaviour in intact tissues to single cell sequencing. The method, which relies on the use of a transgenic strain, was demonstrated for cell migration in mouse airway regeneration. It begins to bridge the gap between cellular and molecular phenotyping of single cells but the authors should be clearer the limitations of the technique.

      (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 name with the authors.)

    Reviewed by eLife