eLife

Latest preprint reviews

1. The E3 ligase Thin controls homeostatic plasticity through neurotransmitter release repression

   This article has 3 authors:

   1. Martin Baccino-Calace
   2. Katharina Schmidt
   3. Martin Müller

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In the study presented here, the authors used the fruitfly Drosophila melanogaster to identify a new molecular regulator - the E3 ubiquitin ligase Thin - of presynaptic homeostatic plasticity (PHP), a process where synaptic signaling between motorneurons and muscle cells is dynamically adapted to compensate exogenously imposed changes in synapse strength. Based on a very substantial set of high quality data, the authors propose that Thin functions presynaptically during PHP, that presynaptic thin negatively regulates neurotransmitter release under baseline conditions by limiting the number of release-ready synaptic vesicles, and that Thin controls transmitter release by regulating Dysbindin, a schizophrenia-susceptibility gene required for PHP. The authors' conclusion is that Thin links protein-degradation-dependent proteostasis of Dysbindin to homeostatic regulation of neurotransmitter release. The major claims of the paper are well supported by the data, but alternative hypotheses cannot yet be unequivocally excluded.

     (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. Framework for rapid comparison of extracellular vesicle isolation methods

   This article has 7 authors:

   1. Dmitry Ter-Ovanesyan
   2. Maia Norman
   3. Roey Lazarovits
   4. Wendy Trieu
   5. Ju-Hyun Lee
   6. George M Church
   7. David R Walt

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript describes a framework for rapidly quantifying relative extracellular vesicle (EV) yield and purity across isolation methods, with a focus on using size exclusion chromatography (SEC) for EV isolation from small volumes of pooled plasma and cerebrospinal fluid (CSF) samples. The authors used single molecule array (Simoa) assays for the quantification of EVs using three tetraspanins (CD9, CD63, and CD81), and report the outcomes of assessing EV yields and purity with respect to albumin by various SEC parameters (Sepharose size, column length, fractions collected). This is the first demonstration of the use of Simoa with three commonly used tetraspanins to measure EVs from small volumes of CSF, of great relevance to human CSF biomarker studies, but these methods could also be applied to compare EV isolation methods from other fluids such as cell culture media.

     (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

3. Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae

   This article has 7 authors:

   1. Tingting Zhao
   2. Irina O Vvedenskaya
   3. William KM Lai
   4. Shrabani Basu
   5. B Franklin Pugh
   6. Bryce E Nickels
   7. Craig D Kaplan

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Kaplan and colleagues build upon their earlier work using genetic phenotypes to find and analyze mutations that determine how mRNA start sites are chosen. Here they provide convincing genetic evidence supporting a model in which the Transcription Factor II H (TFIIH) protein complex pushes downstream DNA back into the RNA polymerase active site, creating a window within which the polymerase can choose particular start sites. This will primarily interest those in the transcription field who are thinking about initiation mechanisms.

     (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. Single-nucleus transcriptomic analysis of human dorsal root ganglion neurons

   This article has 5 authors:

   1. Minh Q Nguyen
   2. Lars J von Buchholtz
   3. Ashlie N Reker
   4. Nicholas JP Ryba
   5. Steve Davidson

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this work, Minh Nguyen and colleagues performed single nuclear RNAseq of human dorsal root ganglion (DRG) neurons and classified them into 15 clusters. A bioinformatic comparison to mouse lumbar DRG single nucleus sequencing results is also described. The importance of reporting the single nucleus or single cell molecular profiles of human DRG cannot be overstated. Proper molecular targeting of therapeutics requires knowing this information. Given that the field is just starting to understand the human specific molecular signature of primary somatosensory neurons using single cell/nuclear RNAseq, this study is important and timely, providing one of the first gene expression databases of individual human DRG neurons.

     (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. Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH

   This article has 8 authors:

   1. Theresa Hwang
   2. Sara S Parker
   3. Samantha M Hill
   4. Robert A Grant
   5. Meucci W Ilunga
   6. Venkatesh Sivaraman
   7. Ghassan Mouneimne
   8. Amy E Keating

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript introduces a new molecular screen, MassTitr, to screen for long (36-mer) peptides derived from the human proteome that can bind a specific target. The method is demonstrated using the EVH1 domain of the actin-associated ENAH protein as target. About 100 peptides were isolated, and further analysis identified sequence features that contribute to the binding of the EVH1 domain by these peptides. The human proteome contains many short linear motifs of 4-6 residues that are critical for protein-protein interactions. The work here helps to better understand how the sequence surrounding such motifs contributes to protein-protein interactions.

     (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

6. Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

   This article has 7 authors:

   1. Tania López-Hernández
   2. Koh-ichiro Takenaka
   3. Yasunori Mori
   4. Pornparn Kongpracha
   5. Shushi Nagamori
   6. Volker Haucke
   7. Shigeo Takamori

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Local recycling of synaptic vesicles is required to maintain neurotransmission via clathrin-mediated endocytosis and clathrin-independent ultrafast endocytosis. Clathrin also plays a role in ultrafast endocytosis to regenerate vesicles from a recycling endosome. Here the authors have further tested the role of clathrin and clathrin adaptors in synaptic vesicle endocytosis. This paper raises the interesting possibility that adaptor protein AP-2 but not clathrin contributes to the endocytosis of synaptic vesicle proteins. There are some concerns about differential knockdown of clathrin and AP-2 but if the authors can resolve these, this would be an important result.

     (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

7. Dynamics and variability in the pleiotropic effects of adaptation in laboratory budding yeast populations

   This article has 4 authors:

   1. Christopher W Bakerlee
   2. Angela M Phillips
   3. Alex N Nguyen Ba
   4. Michael M Desai

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The pleiotropic effects of beneficial mutations have been characterized in various settings, but it is less clear whether and how these pleiotropic patterns change over the course of evolution. Using a technically innovative and intensive experimental design with evolving yeast populations, the authors show that patterns of pleiotropy depend on the evolution environment and can change and vary substantially over relatively short timescales. They also find a surprising amount of variation among replicate populations that increases over time, so generalism or specialism is not deterministic. These technical and conceptual strengths were diminished by insufficient focus on the details of certain treatments that are demonstrative of these broader findings, making the take-home message somewhat unclear.

     (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

8. Temporo-cerebellar connectivity underlies timing constraints in audition

   This article has 5 authors:

   1. Anika Stockert
   2. Michael Schwartze
   3. David Poeppel
   4. Alfred Anwander
   5. Sonja A Kotz

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors demonstrate deficits in perceptual tests related to fine-time perception in non-speech and speech sounds in a group of patients with stroke aphasia compared to a control group without a lesion. An area in left auditory cortex is defined that is essential for fine-time perception that is shown in a separate group of normal subjects to other areas including the cerebellum. The work in interesting in suggesting an anatomical basis for interaction between cortical and cerebellar system for perceptual timing.

     (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. Gaps in global wildlife trade monitoring leave amphibians vulnerable

   This article has 3 authors:

   1. Alice C Hughes
   2. Benjamin Michael Marshall
   3. Colin T Strine

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     These are pressing times for nature, standing alone the impact of multiple (human-based) ecological stressors. Wildlife trade is one of these stressors. And, although it is an acute one, it is the easiest solvable global ecological problem. The authors increase dramatically our understanding of legal and illegal trade of amphibians, and offer a wider methodology (however, and importantly, not necessarily a more complex one) to gain a deeper understanding of the causes and consequences) of amphibians' trade. The work will inspire in conservation biologists similar approaches to learn about the trade of other taxa.

     (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

10. Structural insights into the activation of human calcium-sensing receptor

    This article has 14 authors:

    1. Xiaochen Chen
    2. Lu Wang
    3. Qianqian Cui
    4. Zhanyu Ding
    5. Li Han
    6. Yongjun Kou
    7. Wenqing Zhang
    8. Haonan Wang
    9. Xiaomin Jia
    10. Mei Dai
    11. Zhenzhong Shi
    12. Yuying Li
    13. Xiyang Li
    14. Yong Geng

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This manuscript reveals new molecular details about the human calcium sensing receptor (CaSR), a G protein-coupled receptor that maintains calcium homeostasis and is involved in pathological states. This study, together with other recent structural work on this molecule, will have important implications for the design of molecules that control CaSR activity and treat human disease.

      (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