eLife

Latest preprint reviews

1. Paraxial mesoderm organoids model development of human somites

   This article has 6 authors:

   1. Christoph Budjan
   2. Shichen Liu
   3. Adrian Ranga
   4. Senjuti Gayen
   5. Olivier Pourquié
   6. Sahand Hormoz

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Budjan et al. describe an organoid protocol to obtain somite-like structures from human iPSCs. Using defined culture media, the authors describe the formation after 5 days in vitro of organoids that express a variety of PSM differentiation markers, such as the segmentation clock gene Hes7 and Pax3. Optimization of their culture conditions and transcription analyses of what they name their "somitoid" system revealed that their culture system recapitulates the time course of expression markers typically observed along PSM and somite early differentiation. Furthermore, somitoid reacted to Shh activation by activating sclerotomal markers Pax1 and 9.

     (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. Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain

   This article has 8 authors:

   1. Mitul Desai
   2. Jitendra Sharma
   3. Adrian L Slusarczyk
   4. Ashley A Chapin
   5. Robert Ohlendorf
   6. Agata Wisniowska
   7. Mriganka Sur
   8. Alan Jasanoff

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript will be of interest to readers in the field of magnetic resonance imaging and responsive imaging probes. In this work, a new imaging probe is designed and applied in proof-of-principle animal models, with future promise for relevance in models that have higher relevance to 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. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

3. Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

   This article has 4 authors:

   1. Oscar Urtatiz
   2. Amanda Haage
   3. Guy Tanentzapf
   4. Catherine D Van Raamsdonk

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     In this manuscript, the authors study the discrepancy between the frequency of mutations in Gq alpha subunit (GNAQ and its paralogue GNA11) in uveal vs cutaneous melanoma. They hypothesize that the restriction of GNAQ and GNA11 mutations to non-epithelial melanomas is due to epidermal factors, which convert the impact of GNAQ Q209L mutation from being oncogenic to being inhibitory to melanocyte survival and proliferation, and reduce the maintenance, rather than the establishment of interfollicular epithelial melanocytes. This work provides new insights into the poorly understood difference in mutation frequency in different melanoma types.

     (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. Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in Saccharomyces cerevisiae

   This article has 5 authors:

   1. Fernando Rodrigo Rosas Bringas
   2. Sonia Stinus
   3. Pien de Zoeten
   4. Marita Cohn
   5. Michael Chang

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study investigates the tolerance to change in the sequence of telomere repeats, by analyzing a strain expressing mutant TLC1, the RNA component of the telomerase. The authors conclude that Rif2 protects telomere ends in the absence of RAP1 by inhibiting MRX and promoting Rad51-dependent homologous recombination to maintain telomere homeostasis. The study clarifies the role of Rif2 in telomere homeostais and describes how cells can extend telomeres and control senescence in the absence of Rap1 binding to telomeres. The possibility of coping with telomere sequence modification through flexibility and redundancy of capping proteins is of general interest in terms of telomere evolution.

     (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. Bidirectional synaptic plasticity rapidly modifies hippocampal representations

   This article has 7 authors:

   1. Aaron D Milstein
   2. Yiding Li
   3. Katie C Bittner
   4. Christine Grienberger
   5. Ivan Soltesz
   6. Jeffrey C Magee
   7. Sandro Romani

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript uses a combination of high-quality in vivo electrophysiology and modelling to demonstrate that Behavioural Time Scale Plasticity (BTSP) is bidirectional, and the amplitude and direction of this plasticity are dictated by the current weight of the inputs and not by the correlated activity of pairs of neurons. These findings challenge our current views on synaptic plasticity, which are primarily based on Hebb's concept. In addition, the network model used in this study demonstrates that this type of plasticity can rapidly reshape population activity to respond to environmental clues. This study will be of interest to the broad neuroscience audience and foster new ideas on biological and artificial learning.

     (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. 3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography

   This article has 11 authors:

   1. Marius Reichardt
   2. Patrick Moller Jensen
   3. Vedrana Andersen Dahl
   4. Anders Bjorholm Dahl
   5. Maximilian Ackermann
   6. Harshit Shah
   7. Florian Länger
   8. Christopher Werlein
   9. Mark P Kuehnel
   10. Danny Jonigk
   11. Tim Salditt

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript aims to characterize cardiac tissues from patients who developed Covid-19. The authors studied pathological and normal tissues using microtomography scans performed at different resolution scales. Starting on the reconstructed volumes, special automatic analytical procedures were developed to extract some quantitative structural parameters about the samples themselves. This characterization method was used previously in the study of murine heart models. The main outcome of the research is that there are some well defined characteristics found in tissues of COVID patients that are not revealed in other pathological and normal samples.

     (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

7. Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study

   This article has 4 authors:

   1. Wuqing Huang
   2. Jun Xiao
   3. Jianguang Ji
   4. Liangwan Chen

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     There are mixed results from studies of COVID-19 outcomes in patients treated with statins and there are multiple confounders. The authors use two Mendelian randomization methods to explore the association between HMGCoA reductase inhibitors (statins) and other lipid lowering drugs and outcomes and find that increased expression of HMGCoA reductase and HMGCoA reductase mediated LDL cholesterol increase hospitalization risk. This makes it possible but does not prove that statins could improve outcomes which will be of broad interest.

     (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, ScreenIT

8. Ligand binding remodels protein side-chain conformational heterogeneity

   This article has 5 authors:

   1. Stephanie A Wankowicz
   2. Saulo H de Oliveira
   3. Daniel W Hogan
   4. Henry van den Bedem
   5. James S Fraser

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This work attempts to extract information about protein thermodynamics from X-ray crystallography data, which is a challenging problem. This work presents a comprehensive examination of the structural transitions associated with small molecule binding to proteins. The heterogenous pattern of order parameter changes in response to ligand binding implies that the approach is identifying new information. This work offers insights into ligand binding affinity and specificity mechanisms, suggesting that distal (allosteric) perturbations represent a possible avenue to modulate protein function.

     (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. AR-V7 exhibits non-canonical mechanisms of nuclear import and chromatin engagement in castrate-resistant prostate cancer

   This article has 12 authors:

   1. Seaho Kim
   2. CheukMan C Au
   3. Mohd Azrin Bin Jamalruddin
   4. Naira Essam Abou-Ghali
   5. Eiman Mukhtar
   6. Luigi Portella
   7. Adeline Berger
   8. Daniel Worroll
   9. Prerna Vatsa
   10. David S Rickman
   11. David M Nanus
   12. Paraskevi Giannakakou

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Truncated splice variants of the androgen receptor (AR) lacking a ligand-binding domain are thought to contribute to therapeutic resistance to antiandrogens in advanced prostate cancer. In this manuscript, the authors show that AR-V7, the most well-studied such truncated variant, displays a different mechanism of nuclear targeting and interaction with chromatin compared to the full-length AR. This work provides new insights into how AR-V7 may contribute to the pathology of Castrate-Resistant Prostate Cancer and will be of interest to researchers trying to improve prostate cancer therapies.

     (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. Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice

    This article has 10 authors:

    1. Dan Luo
    2. Ni Fan
    3. Xiuying Zhang
    4. Fung Yin Ngo
    5. Jia Zhao
    6. Wei Zhao
    7. Ming Huang
    8. Ding Li
    9. Yu Wang
    10. Jianhui Rong

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This paper is of interest to a broad audience of cell biologists, pharmacologists and researchers who work in metabolic diseases. The work provides substantial new insights into the mechanism of action for a plant derived pentacyclic triterpene called celastrol elastrol, in effectively reducing the high fat diet induced tissue hypertrophy in mouse liver and adipose. A series of compelling experiments depict the site of covalent inhibition of the ER stress sensor GRP78 as essential for the beneficial effects in-vivo, supporting the main 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. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife