Evaluated articles

Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment

1. Yanan Chen
2. Rejani B Kunjamma
3. Molly Weiner
4. Jonah R Chan
5. Brian Popko

• Curated by eLife

  Evaluation Summary:

  This is an elegantly conducted study showing integrated stress response (ISR) contributes to protection of oligodendrocytes in the remyelination process in the setting of an inflammatory environment. The authors use both genetic (GADD43KO) and pharmacological approaches (Sephin1) to study ISR in demyelination animal models. The data are convincing and have important clinical implications for multiple sclerosis and other diseases. The reviewers agree that revisions are needed for the sake of presentation, clarity, rationale, and interpretation of datasets.

  (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

Keratinocyte PIEZO1 modulates cutaneous mechanosensation

1. Alexander R Mikesell
2. Olena Isaeva
3. Francie Moehring
4. Katelyn E Sadler
5. Anthony D Menzel
6. Cheryl L Stucky

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to readers in the field of somatosensation. The identification that a common type of skin cell responds to mechanical force using a specific molecular receptor called Piezo1 is an important contribution to our understanding of mechanotransduction. A combination of conditional gene knockout with physiological and behavioral assays provides intriguing evidence that communication between skin and nerves is important for normal touch sensation, a conclusion that if further supported by additional data could become a fundamental discovery.

  (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

Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans

1. Mor Levi-Ferber
2. Rewayd Shalash
3. Adrien Le-Thomas
4. Yehuda Salzberg
5. Maor Shurgi
6. Jennifer IC Benichou
7. Avi Ashkenazi
8. Sivan Henis-Korenblit

• Curated by eLife

  Evaluation Summary:

  The authors of this manuscript previously showed that ER stress, and in particular the ER stress sensor Ire1, regulates transdifferentiation in C. elegans, leading to the ectopic differentiation of germline cells. In this follow-up manuscript, the authors present several lines of evidence supporting the idea that Ire1 modules these effects through degrading a novel mRNA substrate flp6. The authors identify the neurons and neuromodulators that affect accumulation of abnormal germline cells. The reviewers agreed that the discovery that flp6 is a regulated Ire-1-dependent decay target in C. elegans, and the demonstration of a non-cell-autonomous effect of Ire1 activity, are novel and likely to be of interest to a broad readership. However, more evidence is required to support some of 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish

1. Marion Rosello
2. Juliette Vougny
3. François Czarny
4. Marina C Mione
5. Jean-Paul Concordet
6. Shahad Albadri
7. Filippo Del Bene

• Curated by eLife

  Evaluation Summary:

  The manuscript by Rosello et al. represents a major advance in implementation of cutting-edge genome editing methodologies in the zebrafish. The study seeks to describe optimized tools for precise base editing in zebrafish and to demonstrate their effective application. Overall, this study demonstrates that cytosine base editing is an efficient and powerful method for introducing precise in vivo edits into the zebrafish genome, and will be of interest to scientists who use zebrafish and other genetic systems to model human development and 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

Inversion of pheromone preference optimizes foraging in C. elegans

1. Martina Dal Bello
2. Alfonso Pérez-Escudero
3. Frank C Schroeder
4. Jeff Gore

Reviewed by eLife

Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8

1. Hsiang-Chun Chang
2. Jason Solomon Shapiro
3. Xinghang Jiang
4. Grant Senyei
5. Teruki Sato
6. Justin Geier
7. Konrad T Sawicki
8. Hossein Ardehali

• Curated by eLife

  Evaluation Summary:

  This is an interesting manuscript and experiments generally make their point on Alr effects. However, additional data would strengthen the paper with respect to the relative roles of cytoplasmic vs mitochondrial isoforms as would mitochondrial function studies.

  (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

A mobile genetic element increases bacterial host fitness by manipulating development

1. Joshua M Jones
2. Ilana Grinberg
3. Avigdor Eldar
4. Alan D Grossman

• Curated by eLife

  Evaluation Summary:

  All the reviewers were in agreement that this is an exceptionally rigorous paper that sets an important precedent for how mobile genetic elements can influence host 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 #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

1. Anthony A Ruberto
2. Aline Gréchez-Cassiau
3. Sophie Guérin
4. Luc Martin
5. Johana S Revel
6. Mohamed Mehiri
7. Malayannan Subramaniam
8. Franck Delaunay
9. Michèle Teboul

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest in the fields of circadian biology and metabolic physiology. It provides a molecular mechanism for protection against development of fatty liver in response to high sugar consumption. Quality data support the key claims of the paper in each of the main research areas (circadian biology and metabolism) but additional efforts are needed to integrate the two parts. The current study does not thoroughly connect the in vitro and in vivo findings and misses the opportunity to fully characterize the role of KLF10 in circadian regulation in response to excessive sugar consumption.

  (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

Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction

1. Nadiatou T Miningou Zobon
2. Joanna Jędrzejewska-Szmek
3. Kim T Blackwell

Reviewed by eLife

Endothelial cell senescence exacerbates pulmonary hypertension through Notch-mediated juxtacrine signaling

1. Risa Ramadhiani
2. Koji Ikeda
3. Kazuya Miyagawa
4. Gusty Rizky Teguh Ryanto
5. Naoki Tamada
6. Yoko Suzuki
7. Ken-ichi Hirata
8. Noriaki Emoto

Reviewed by eLife

A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans

1. Pille Hallast
2. Laura Kibena
3. Margus Punab
4. Elena Arciero
5. Siiri Rootsi
6. Marina Grigorova
7. Rodrigo Flores
8. Mark A Jobling
9. Olev Poolamets
10. Kristjan Pomm
11. Paul Korrovits
12. Kristiina Rull
13. Yali Xue
14. Chris Tyler-Smith
15. Maris Laan

• Curated by eLife

  Evaluation Summary:

  This study presents extensive genetic analysis of a relatively large cohort of men with idiopathic infertility, with considerable accompanying andrological phenotypic data. Through careful step-by-step investigations, an inversion variant is identified as a risk factor for subsequent deletion variants that can lead to substantially increased risk of impaired spermatogenesis, on an age-structured basis, relative to non-carriers. This work will be of particular interest to the reproductive genetics field, but also has wide ranging implications for colleagues interested in common disease genetics, meiosis, structural variation, dosage sensitivity, and sex chromosome evolution. As part of the most comprehensive investigation of AZFc micro-deletions and structural variation to date, the authors have identified a novel structural variant of the Y-chromosome that predisposes to spermatogenic failure and provided clear guidelines for genetic counseling.

  (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

Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification

1. Ka-Cheuk Liu
2. Alethia Villasenor
3. Maria Bertuzzi
4. Nicole Schmitner
5. Niki Radros
6. Linn Rautio
7. Kenny Mattonet
8. Ryota L Matsuoka
9. Sven Reischauer
10. Didier YR Stainier
11. Olov Andersson

• Curated by eLife

  Evaluation Summary:

  This is an elegant study demonstrating the emergence of mesoderm-derived beta-like cells following beta-cell ablation in an endothelial cell deficient context. These findings will be of interest to scientists in the areas of regeneration and reprogramming, as they reveal a previously unknown degree of germ layer plasticity in the embryo. In the long term the study has potential impact in the diabetes field, as it reveals a novel path for redirecting somatic cells into insulin-producing cells in an in vivo context.

  (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

Decoding subjective emotional arousal from EEG during an immersive virtual reality experience

1. Simon M Hofmann
2. Felix Klotzsche
3. Alberto Mariola
4. Vadim Nikulin
5. Arno Villringer
6. Michael Gaebler

• Curated by eLife

  Summary: Hofmann et al. investigate the link between two phenomena, emotional arousal and cortical alpha activity. Although alpha activity is tightly linked to the first reports of electric activity in the brain nearly 100 years ago, a comprehensive characterization of this phenomenon is elusive. One of the reasons is that EEG, the major method to investigate electric activity in the human brain, is susceptible to motion artifacts and, thus, mostly used in laboratory settings. Here, the authors combine EEG with virtual reality (VR) to give experimental participants a roller-coaster ride with high immersion. The ride, literally, leads to large ups and downs in emotional arousal, which is quantified by the subjects during a later rerun. Three different decoding methods were evaluated (Source Power Comodulation, Common Spatial Patterns, and Long Short-Term Memory Recurrent Neural Networks), each of which demonstrated above-chance levels of performance, substantiating a link between lower levels of parietal/occipital alpha and subjective arousal in a quasi-naturalistic setting.

  The reviewers both expressed some enthusiasm for the MS:

  The study is timely and makes an important contribution to our understanding of the relation of emotions and sensory processing

  Of potentially great interest to a broad audience

  The embedding in historic literature is excellent. I like it a lot.

  This work is notable because the roller-coaster simulation is a well-controlled, yet dynamic manipulation of arousal, and in its comparison of multiple decoding approaches (that can model the dynamics of affective responses). Indeed, this is an interesting proof of concept that shows it is possible to decode affective experience from brain activity measured during immersive virtual reality.

  Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Morphological and genomic shifts in mole-rat ‘queens’ increase fecundity but reduce skeletal integrity

1. Rachel A Johnston
2. Philippe Vullioud
3. Jack Thorley
4. Henry Kirveslahti
5. Leyao Shen
6. Sayan Mukherjee
7. Courtney M Karner
8. Tim Clutton-Brock
9. Jenny Tung

• Curated by eLife

  Evaluation Summary:

  This manuscript takes a deep dive into the skeletal effects of burrowing and eusocial Damaraland mole rats. By exploring the genetic and skeletal consequences of breeding restricted to a single queen with multiple and closely-timed pregnancies and lactation, this study offers a compelling story that will bolster textbooks on skeletal biology, mammalian evolution, and ethology. The results show the molecular mechanisms driving adaptive plasticity within the unusually expanded lumbar spine and thin limb bones of queens are an adaptive consequence of breeding status.

  (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

Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast

1. Rachael Emily Turner
2. Paul F Harrison
3. Angavai Swaminathan
4. Calvin A Kraupner-Taylor
5. Belinda J Goldie
6. Michael See
7. Amanda L Peterson
8. Ralf B Schittenhelm
9. David R Powell
10. Darren J Creek
11. Bernhard Dichtl
12. Traude H Beilharz

• Curated by eLife

  Evaluation Summary:

  This study aims to provide a comprehensive analysis of factors governing polyadenylation site selection in yeast. Overall, the authors reveal that multiple but distinct inputs including polyadenylation machinery integrity, transcription elongation rate, nucleotide availability and chromatin landscape all contribute to controlling cleavage and polyadenylation.

  (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

The propofol binding sites of prokaryotic voltage-gated sodium channels

1. Elaine Yang
2. Weiming Bu
3. Antonio Suma
4. Vincenzo Carnevale
5. Kimberly C. Grasty
6. Patrick Loll
7. Kellie Woll
8. Natarajan Bhanu
9. Benjamin A. Garcia
10. Roderic G. Eckenhoff
11. Manuel Covarrubias

Reviewed by eLife

An evolutionary model identifies the main evolutionary biases for the evolution of genome-replication profiles

1. Rossana Droghetti
2. Nicolas Agier
3. Gilles Fischer
4. Marco Gherardi
5. Marco Cosentino Lagomarsino

• Curated by eLife

  Summary: The reviewers appreciate that the manuscript presents a simple but compelling model that explains the dynamics of replication origin birth and death, which enhances our understanding of the selection pressures that have shaped the distribution of replication origins. However, both reviewers had a series of concerns.

Reviewed by eLife

The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium

1. Patrick Morley Willoughby
2. Molly Allen
3. Jessica Yu
4. Roman Korytnikov
5. Tianhui Chen
6. Yupeng Liu
7. Isis So
8. Haoyu Wan
9. Neil Macpherson
10. Jennifer A Mitchell
11. Rodrigo Fernandez-Gonzalez
12. Ashley EE Bruce

• Curated by eLife

  Evaluation Summary:

  Willoughby et al. examine the role of Rab25 in early embryogenesis in zebrafish. They implicate Rab25 activity in abscission and show various defects including delayed epiboly and altered cell behaviors associated with defective acting dynamics. Overall, this is an interesting and well-written paper. However, there are a number of important controls that are missing and some connections such as the implication of membrane recycling that require stronger experimental validation.

  (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

Perception of microstimulation frequency in human somatosensory cortex

1. Christopher L Hughes
2. Sharlene N Flesher
3. Jeffrey M Weiss
4. Michael Boninger
5. Jennifer L Collinger
6. Robert A Gaunt

• Curated by eLife

  Evaluation Summary:

  This paper characterizes percepts evoked by micro-stimulating the somatosensory cortex of a human participant. The study provides some new insight into the organization of the human somatosensory cortex and represents an important step in providing more effective somatosensory feedback for brain-machine interface users.

  (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

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

1. Trygve E Bakken
2. Cindy TJ van Velthoven
3. Vilas Menon
4. Rebecca D Hodge
5. Zizhen Yao
6. Thuc Nghi Nguyen
7. Lucas T Graybuck
8. Gregory D Horwitz
9. Darren Bertagnolli
10. Jeff Goldy
11. Anna Marie Yanny
12. Emma Garren
13. Sheana Parry
14. Tamara Casper
15. Soraya I Shehata
16. Eliza R Barkan
17. Aaron Szafer
18. Boaz P Levi
19. Nick Dee
20. Kimberly A Smith
21. Susan M Sunkin
22. Amy Bernard
23. John Phillips
24. Michael J Hawrylycz
25. Christof Koch
26. Gabe J Murphy
27. Ed Lein
28. Hongkui Zeng
29. Bosiljka Tasic

• Curated by eLife

  Summary: This manuscript provides a comparative analysis of the cell variety present in the dorsal lateral geniculate nucleus (dLGN) of mice, non-human primates, and humans using single-cell/single-nucleus RNA-sequencing (Smart-seq). The study identifies excitatory and inhibitory dLGN cell types in the three species and shows that the different subclasses of inhibitory neurons are relatively similar across species. In contrast, excitatory neurons appear to bear cross-species differences particularly between mouse and primates. The study provides an extensive description of the dLGN neurons, an important visual relay nucleus that has been so far poorly studied. As such, these data are very welcomed and will likely attract the interest of researchers working in visual function and beyond. The strong and creative bioinformatics analysis has uncovered interesting and subtle cross species links between different types of neurons.

  Reviewer #1, Reviewer #2 and Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife