Evaluated articles

Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy

1. Amit Gutwillig
2. Nadine Santana-Magal
3. Leen Farhat-Younis
4. Diana Rasoulouniriana
5. Asaf Madi
6. Chen Luxenburg
7. Jonathan Cohen
8. Krishnanand Padmanabhan
9. Noam Shomron
10. Guy Shapira
11. Annette Gleiberman
12. Roma Parikh
13. Carmit Levy
14. Meora Feinmesser
15. Dov Hershkovitz
16. Valentina Zemser-Werner
17. Oran Zlotnik
18. Sanne Kroon
19. Wolf-Dietrich Hardt
20. Reno Debets
21. Nathan Edward Reticker-Flynn
22. Peleg Rider
23. Yaron Carmi

• Curated by eLife

  Evaluation Summary:

  Although immunotherapy has revolutionized the cancer field, most tumors do not respond, and in those that do respond, acquired resistance is often inevitable. Several mechanisms have been proposed to be involved in acquired resistance to immunotherapy. In the present study, the authors show that tumor cells from multi-cellular structures protect the inner core of tumor cells via the prevention of penetration by lytic molecules. The formation of these structures is mediated by anti-tumor T cells even with tumors that have retained their immunogenic neoantigens. This work identifies a novel possible resistance mechanism to immune-mediated tumor killing.

  (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.)

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Comprehensive machine-learning survival framework develops a consensus model in large-scale multicenter cohorts for pancreatic cancer

1. Libo Wang
2. Zaoqu Liu
3. Ruopeng Liang
4. Weijie Wang
5. Rongtao Zhu
6. Jian Li
7. Zhe Xing
8. Siyuan Weng
9. Xinwei Han
10. Yu-ling Sun

• Curated by eLife

  Evaluation Summary:

  This work sets out to develop a better machine learning-based predictor of survival/prognosis for patients diagnosed with pancreatic cancer, by developing a large combinatorial family of machine learning methods based on a high-dimensional set of -omics and other patient data features; using ten publicly available data sets. A reduced set of features (giving rise to a signature called AIDPS that involves 9 genes) was identified. Unfortunately, the authors used all ten data sets both in the discover stage and in the validation stage of their study. There was also a large mismatch between the initial number of covariates (15,288 genes) and the number of samples (n=1280). The combinatorial ensemble of ML models makes for an unwieldy methodology that is difficult to interpret or duplicate.

  (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.)

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Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection

1. Ryan Zander
2. Achia Khatun
3. Moujtaba Y Kasmani
4. Yao Chen
5. Weiguo Cui

• Curated by eLife

  Evaluation Summary:

  This study by Zander et al provides a valuable transcriptomic resource of murine CD4 T cell subsets in chronic viral infection. This study will be of broad interest to a wide range of researchers focused on studying CD4 T cell 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. The reviewers remained anonymous to the authors.)

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Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans

1. Amy L Roberts
2. Alessandro Morea
3. Ariella Amar
4. Antonino Zito
5. Julia S El-Sayed Moustafa
6. Max Tomlinson
7. Ruth CE Bowyer
8. Xinyuan Zhang
9. Colette Christiansen
10. Ricardo Costeira
11. Claire J Steves
12. Massimo Mangino
13. Jordana T Bell
14. Chloe CY Wong
15. Timothy J Vyse
16. Kerrin S Small

• Curated by eLife

  Evaluation Summary:

  Women are a mosaic of two population of cells, one with the paternal X-chromosome and the other with the maternal one in the active state due to random X-chromosome inactivation (XCI) that occurs during embryogenesis. During aging, one of the two populations dominates the other in a significant proportion of women. This skewing of XCI is of unknown etiology and its impact on health remains enigmatic. In this study, Amy L. Robert et al, demonstrate that skewing may not be benign and it is associated with a modest but significant increased risk of cardiovascular disease and cancer.

  (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.)

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Disruption in structural–functional network repertoire and time-resolved subcortical fronto-temporoparietal connectivity in disorders of consciousness

1. Rajanikant Panda
2. Aurore Thibaut
3. Ane Lopez-Gonzalez
4. Anira Escrichs
5. Mohamed Ali Bahri
6. Arjan Hillebrand
7. Gustavo Deco
8. Steven Laureys
9. Olivia Gosseries
10. Jitka Annen
11. Prejaas Tewarie

• Curated by eLife

  Evaluation Summary

  This study aims to characterise the brain dynamics of different disorders of consciousness by studying patients in a minimally conscious state and those with unresponsive wakefulness syndrome, along with healthy controls. The authors apply elegant analyses to the dynamics of brain functional connectivity to successfully discriminate between healthy controls and patients, revealing reduced metastability and a contracted network repertoire in disorders of consciousness. Overall, the study provides important new information on the mechanisms of disorders of consciousness and the functional brain networks involved.

  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.

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A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis

1. Rodrigo Meléndez García
2. Olivier Haccard
3. Albert Chesneau
4. Hemalatha Narassimprakash
5. Jérôme Roger
6. Muriel Perron
7. Kathrin Marheineke
8. Odile Bronchain

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest within the fields of DNA replication, developmental biology and oncology. Focusing on the YAP protein, a major regulator of tissue growth and repair, it identifies an interesting new role in DNA replication dynamics, beyond its known role in gene transcription regulation. A series of experimental manipulations support the key claims of the paper. Additional control experiments, as well as mechanistic insight into how RIF1 and YAP interact, and insight into how that interaction influences replication timing would make the paper stronger.

  (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.)

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1. Guang Wang
2. Yong-Feng Wang
3. Jiang-Lan Li
4. Ru-Ji Peng
5. Xin-Yin Liang
6. Xue-Dong Chen
7. Gui-Hua Jiang
8. Jin-Fang Shi
9. Yang-Hu Si-Ma
10. Shi-Qing Xu
11. 苏州大学苏州医学院基础医学与生物科学学院, 江苏 苏州215123, 中国
12. 苏州大学第一附属医院临床检验科, 江苏 苏州215006, 中国
13. School of Biology and Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China
14. Department of Clinical Laboratory, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China

• Curated by eLife

  Evaluation Summary:

  The authors present a manuscript addressing an important unmet need, specifically focused on understanding the effects of high protein on hematopoiesis. This information can be of interest to basic biologists and clinicians who specialize in the areas of various diseases associated with elevated protein concentration (e.g. infections, inflammation, multiple myeloma, renal failure, etc). This is in part what makes for the complexity in studying this entity as the consequences of such disparate diseases are difficult to parcel out as causes of which specific disease manifestations. Furthermore, the presented work is done in an invertebrate model without additional confirmation in other model systems. Taken together, the work, which is plentiful in experiments, provides an incomplete understanding of cause and effect, leading to overinterpretation of results and overstating of derived 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.)

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Diversity of funnel plasmodesmata in angiosperms: the impact of geometry on plasmodesmal resistance

1. Grayson P. Ostermeyer
2. Kaare H. Jensen
3. Aslak R. Franzen
4. Winfried S. Peters
5. Michael Knoblauch

• Curated by eLife

  Evaluation Summary:

  The authors make an important contribution to our understanding of the universal mechanism of unloading of sugars from the phloem (the vascular tissue dedicated to long-distance sugar transport in plants) into root tip cells. Specifically, the authors investigate the pores (called plasmodesmata) present in the cell wall separating phloem cells from those cells into which sugars get unloaded in roots, which they found to have the same characteristic structure in all plant species investigated. The physical properties of these particular plasmodesmata suggest that they are especially suited for efficient and selective phloem unloading. The paper is relevant for audiences studying plant physiology and development. There are a few criticisms of the modelling work.

  (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.)

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Cortical layer‐specific modulation of neuronal activity after sensory deprivation due to spinal cord injury

1. Marta Zaforas
2. Juliana M. Rosa
3. Elena Alonso‐Calviño
4. Elena Fernández‐López
5. Claudia Miguel‐Quesada
6. Antonio Oliviero
7. Juan Aguilar

• Curated by eLife

  Evaluation Summary:

  Zaforas et al. conducted a high-quality study on a very complex topic, using advanced layer-specific neuronal recording techniques. Their findings might be especially interesting for pre-clinical and clinical researchers as well as clinicians in the field of SCI-related sensory pathologies such as neuropathic pain. However, methodological limitations prevent clear mechanistic insight into the underlying causes of their effects.

  (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.)

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Awareness-Dependent Normalization Framework of Visual Bottom-up Attention

1. Shiyu Wang
2. Ling Huang
3. Qinglin Chen
4. Jingyi Wang
5. Siting Xu
6. Xilin Zhang

• Curated by eLife

  Evaluation Summary:

  The study claims to demonstrate an interplay between awareness and bottom-up attention and explains their joint effects within an established normalization framework. How awareness fits into current computational theory is an important and timely undertaking that has a far-reaching impact on our understanding of visual and cognitive function. Although the study uses control experiments and analyses to reinforce their claims, shortcomings in their experimental approach require further clarification and data to adequately support the study's 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.)

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Alpha Oscillations Shape Sensory Representation and Perceptual Sensitivity

1. Ying Joey Zhou
2. Luca Iemi
3. Jan-Mathijs Schoffelen
4. Floris P. de Lange
5. Saskia Haegens

• Curated by eLife

  Evaluation Summary:

  This work investigates how prestimulus alpha neural oscillations differentially modulate sensory signal and noise during visual detection and demonstrates that alpha power correlates with the subject's perceptual discriminability but not with decision criterion, supporting that alpha power modulates sensory signals more strongly than noise. The key conceptual claim is directly related to existing claims in the literature, although this is an unusually elegant experimental demonstration of the phenomenon.

  (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.)

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Predictive Feedback, Early Sensory Representations, and Fast Responses to Predicted Stimuli Depend on NMDA Receptors

1. Sounak Mohanta
2. Mohsen Afrasiabi
3. Cameron P. Casey
4. Sean Tanabe
5. Michelle J. Redinbaugh
6. Niranjan A. Kambi
7. Jessica M. Phillips
8. Daniel Polyakov
9. William Filbey
10. Joseph L. Austerweil
11. Robert D. Sanders
12. Yuri B. Saalmann

• Curated by eLife

  Evaluation Summary:

  In this study, the authors investigated how predictions modulate performance using a combination of pharmacological experiments, high-density EEG, Bayesian modeling, and machine learning. This is an interesting study with a complex set of analyses. The detailed assessment and interpretation of all the findings could be strengthened by providing a more unified and hypotheses-driven approach.

  (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.)

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Mutations affecting the N-terminal domains of SHANK3 point to different pathomechanisms in neurodevelopmental disorders

1. Daniel Woike
2. Emily Wang
3. Debora Tibbe
4. Fatemeh Hassani Nia
5. Antonio Virgilio Failla
6. Maria Kibæk
7. Tinett Martesen Overgård
8. Martin J. Larsen
9. Christina R. Fagerberg
10. Igor Barsukov
11. Hans-Jürgen Kreienkamp

• Curated by eLife

  Evaluation Summary:

  This study identifies a novel Shank3 mutation from individuals with ADHD-like syndrome and tests the impacts of this mutation together with other known Shank3 mutations on inter- and intramolecular protein-protein interactions of Shank3 involving the N-terminal SPN and Ank repeats. The results indicate that Shank3 mutations have diverse impacts on the intramolecular SPN-Ank domains and the interaction of Shank3 with other proteins including delta-catenin, fodrin, and CaMKIIa. Overall, the results of the study are novel and of high quality. Considering the lack of detailed biochemical understanding on various Shank3 mutations associated with PMS, ASD, and schizophrenia, this study is a meaningful step forward in the basic understanding of Shank3 functions and related pathophysiology.

  (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.)

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Motor cortical output for skilled forelimb movement is selectively distributed across projection neuron classes

1. Junchol Park
2. James W. Phillips
3. Jian-Zhong Guo
4. Kathleen A. Martin
5. Adam W. Hantman
6. Joshua T. Dudman

• Curated by eLife

  Evaluation Summary:

  Park and colleagues examined the activity and function of different projection neuron types, pyramidal tract (PT) and intratelencephalic (IT) neurons, in the primary motor cortex using a joystick manipulation task in mice. During forelimb movements, the activity of IT neurons was more correlated with movement kinematics than that of PT neurons was, and inactivation of IT neurons caused larger effects on movement kinematics (amplitude and velocity). The results highlight different activity patterns and functions between PT and IT neurons. Discussion among reviewers focused on two main issues. One centered on the interpretation of the PT neural activity; the second on the evidence underlying the claim of a dissociation between the PT and IT 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. Reviewer #1 agreed to share their name with the authors.)”

Reviewed by eLife

Prenatal environmental conditions underlie alternative reproductive tactics that drive the formation of a mixed-kin cooperative society

1. Shailee S. Shah
2. Dustin R. Rubenstein

• Curated by eLife

  Evaluation Summary:

  This article will be of interest to evolutionary biologists and behavioural ecologists. It aims to quantify the fitness benefits of helping with the breeding attempts of others vs. seeking own breeding attempts via dispersal. It is generally considered that helping is less profitable than breeding, but occurs when superior reproductive options are constrained. Using a long-term dataset of birds, the authors call into question this assumption, and propose that both reproductive tactics can in fact have similar fitness returns, resulting in mixed-kin societies.

  (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.)

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The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands

1. Sebastian Hutchinson
2. Sophie Foulon
3. Aline Crouzols
4. Roberta Menafra
5. Brice Rotureau
6. Andrew D. Griffiths
7. Philippe Bastin

• Curated by eLife

  Evaluation Summary:

  All reviewers think the study will be really valuable for the field, especially after re-writing to include a detailed comparison with results that were previously published. We all appreciate the clear identification of a gamete sub-population, and also thought that the discovery of low activation of all VSG expression sites was intriguing and will be of considerable interest to those in 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. The reviewers all agreed to share their names with the authors.)

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Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

1. Thomas M. Hart
2. Alan P. Dupuis
3. Danielle M. Tufts
4. Anna M. Blom
5. Simon R. Starkey
6. Ryan O. M. Rego
7. Sanjay Ram
8. Peter Kraiczy
9. Laura D. Kramer
10. Maria A. Diuk-Wasser
11. Sergios-Orestis Kolokotronis
12. Yi-Pin Lin

• Curated by eLife

  Evaluation Summary:

  This work builds on previous work by the same team, demonstrating that the bacterial protein CspA, which inactivates host complement by binding to the host complement inhibitor FH, is a determinant of host range for the Lyme disease bacterium. Additionally, the authors present phylogenetic analysis of CspA and related protein sequences, which supports the hypothesis that inactivation of host complement has evolved independently in three bacterial genospecies.

  (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.)

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Quantifying dynamic facial expressions under naturalistic conditions

1. Jayson Jeganathan
2. Megan Campbell
3. Matthew Hyett
4. Gordon Parker
5. Michael Breakspear

• Curated by eLife

  Evaluation Summary

  This paper describes the development and validation of an automatic approach that leverages machine vision and learning techniques to quantify dynamic facial expressions of emotion. The potential clinical and translational significance of this automated approach is then examined in a "proof-of-concept" follow-on study, which leveraged video recordings of depressed individuals watching humorous and sad video clips.

  (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.)

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Maternal H3K36 and H3K27 HMTs protect germline development via regulation of the transcription factor LIN-15B

1. Chad Steven Cockrum
2. Susan Strome

• Curated by eLife

  Evaluation Summary:

  This study provides a compelling and significant advance on the understanding of how gene regulation by the histone methyltransferase MES-4 underlies germ cell survival in C. elegans, with the major claims being nicely substantiated. The critical and surprising finding is that the degeneration of mes-4 mutant primordial germ cells is due to inappropriate upregulation of genes on the silenced X chromosome, and not failure to activate germline-expressed genes, though reduced levels of germline gene expression were observed. An X-linked target of mes-4, lin-15b, is necessary for the degeneration phenotype. The work could be improved by clarification of the relationship between X and autosomal gene expression, especially in consideration with the action of the other histone methyltransferase MET-1, but otherwise it is excellent.

  (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.)

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Role of immigrant males and muzzle contacts in the uptake of a novel food by wild vervet monkeys

1. Pooja Dongre
2. Gaëlle Lanté
3. Mathieu Cantat
4. Charlotte Canteloup
5. Erica van de Waal

• Curated by eLife

  Evaluation Summary:

  Dongre et al. build on previous social learning research on wild vervet monkeys to investigate the role of a particular social behaviour, muzzle-muzzle contact, in aiding the acceptance of a novel food and provide interesting observations on the potential for male monkeys immigrating from one social group to another in spreading this novel behaviour. With a more robust and transparent analysis, this manuscript has the potential to provide significant insights into innovation and social learning in animals.

  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