Evaluated articles

Environmental drivers of disease depend on host community context

1. Fletcher W. Halliday
2. Mikko Jalo
3. Anna-Liisa Laine

• Curated by eLife

  Evaluation Summary:

  This paper provides a framework for disentangling the direct vs. indirect effects of environment on disease, which should be of broad interest across domains of ecology, epidemiology and plant biology. The authors validate this framework with a well-designed field study of plant leaf disease across a large elevational gradient. Overall, the data analyses are appropriate, but a few aspects of interpretations could be improved.

  (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

The discriminatory power of the T cell receptor

1. Johannes Pettmann
2. Anna Huhn
3. Enas Abu Shah
4. Mikhail A Kutuzov
5. Daniel B Wilson
6. Michael L Dustin
7. Simon J Davis
8. P Anton van der Merwe
9. Omer Dushek

• Curated by eLife

  Evaluation Summary:

  This paper will be of considerable interest to anybody focusing on highly sensitive T cell antigen recognition. It uses an extended experimental protocol and analytical methods to assess very low T cell receptor binding affinities, and to determine how T cells discriminate between self- and non-self antigens. The main conclusions are well supported by the presented analysis and provide a novel view on a previously considered concept.

  (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 interaction between endogenous GABA, functional connectivity, and behavioral flexibility is critically altered with advanced age

1. Kirstin-Friederike Heise
2. Laura Rueda-Delgado
3. Sima Chalavi
4. Bradley R. King
5. Thiago Santos Monteiro
6. Richard A. E. Edden
7. Dante Mantini
8. Stephan P. Swinnen

Reviewed by eLife

Characterization of cephalic and non-cephalic sensory cell types provides insight into joint photo- and mechanoreceptor evolution

1. Roger Revilla-i-Domingo
2. Vinoth Babu Veedin Rajan
3. Monika Waldherr
4. Günther Prohaczka
5. Hugo Musset
6. Lukas Orel
7. Elliot Gerrard
8. Moritz Smolka
9. Alexander Stockinger
10. Matthias Farlik
11. Robert J Lucas
12. Florian Raible
13. Kristin Tessmar-Raible

• Curated by eLife

  Evaluation Summary:

  This manuscript presents an investigation of receptors in the trunk of Platynereis annelids that express genes involved in both photoreception (e.g. r-Opsin) and mechanosensation. This is particularly interesting in light of other work in model organisms like flies that uncovered broadly similar results. The authors compare gene expression of fly Johnston Organ cells and mouse hearing cells to the worm receptors. Because Platynereis is distantly related to flies and mice, the authors suggest this "hybrid" sensory receptor could be very old and homologous across many animals. The question of what role r-Opsins play outside of photoreceptors is an interesting one that remains poorly understood.

  (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 #4 agreed to share their names with the authors.)

Reviewed by eLife

Separable pupillary signatures of perception and action during perceptual multistability

1. Jan W Brascamp
2. Gilles de Hollander
3. Michael D Wertheimer
4. Ashley N DePew
5. Tomas Knapen

• Curated by eLife

  Evaluation Summary:

  Pupillometry is an increasingly accessible tool for the non-invasive readout of brain activity. However, our understanding of pupil-control circuits and of the relationship between changes in pupil size and perception, cognition or action is incomplete. Therefore, any measurements that further this understanding are of great interest to a wide audience in psychology and neurobiology. This study used pupillometry to explore the neural processing underlying perception and dissociate them from action-related neural processing. Results reveal changes in pupil size that are reliably different depending on the task. Such approaches can be very useful in deciphering which of the myriad factors that can affect pupil size are active under specific, controlled conditions.

  (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

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1

1. Naoki Yamawaki
2. Martinna G Raineri Tapies
3. Austin Stults
4. Gregory A Smith
5. Gordon MG Shepherd

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to those studying the sensorimotor functions of the hand and forelimb. It traces the anatomy and strength of excitatory pathways from the spinal cord, through the brainstem, thalamus, somatosensory and motor cortex, and descending outputs. The methods are contemporary, and include multiple viral tracing, genetic targeting, and transsynaptic strategies, optogenetic and electrophysiological methods; the data are compelling; and the paper is clear and concise.

  (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

Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time

1. A Sarah Walker
2. Emma Pritchard
3. Thomas House
4. Julie V Robotham
5. Paul J Birrell
6. Iain Bell
7. John I Bell
8. John N Newton
9. Jeremy Farrar
10. Ian Diamond
11. Ruth Studley
12. Jodie Hay
13. Karina-Doris Vihta
14. Timothy EA Peto
15. Nicole Stoesser
16. Philippa C Matthews
17. David W Eyre
18. Koen B Pouwels
19. COVID-19 Infection Survey team

• Curated by eLife

  Evaluation Summary:

  The authors present a systematic and complete study of Ct (cycle threshold) values in RT-PCR tests and gene-specific positivity for the UK ONS infection survey. There are very few datasets like this for any viral pathogen, regardless of pandemics. The patterns are fascinating and thought-provoking.

  (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

Tachykinin signaling inhibits task-specific behavioral responsiveness in honeybee workers

1. Bin Han
2. Qiaohong Wei
3. Fan Wu
4. Han Hu
5. Chuan Ma
6. Lifeng Meng
7. Xufeng Zhang
8. Mao Feng
9. Yu Fang
10. Olav Rueppell
11. Jianke Li

• Curated by eLife

  Evaluation Summary:

  The authors provide convincing evidence that tachykinin signaling is involved in regulating response thresholds of task-specific stimuli only in the respective behavioral specialist. For example tachykinin signaling affects responses to pollen in pollen foragers and responses to larval chemical cues only in nurse bees. The study highlights the importance of peptide signaling in social behaviors in insects for the first time.

  (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

Database for drug metabolism and comparisons, NICEdrug.ch, aids discovery and design

1. Homa MohammadiPeyhani
2. Anush Chiappino-Pepe
3. Kiandokht Haddadi
4. Jasmin Hafner
5. Noushin Hadadi
6. Vassily Hatzimanikatis

• Curated by eLife

  Evaluation Summary:

  In this study, the authors proposed a new web service/tool and its database, NICEdrug.ch, to be used in the fields of drug discovery and repurposing with the exploration of the metabolic fate of small molecules. The study is timely and will potentially have a high impact as metabolic evaluation of drugs/compounds is a critical topic that is still understudied.

  (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

Phases of cortical actomyosin dynamics coupled to the neuroblast polarity cycle

1. Chet Huan Oon
2. Kenneth E Prehoda

• Curated by eLife

  Evaluation Summary:

  Oon and Prehoda report pulsatile contraction of apical membrane in the process of Par protein polarization in Drosophila neuroblasts. This explains how/why actin filament was required to localize/polarize Par complex. This very much resembles the observation in C. elegans embryos, and nicely unifies observations across systems.

  (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

Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation

1. Mart M Lamers
2. Anna Z Mykytyn
3. Tim I Breugem
4. Yiquan Wang
5. Douglas C Wu
6. Samra Riesebosch
7. Petra B van den Doel
8. Debby Schipper
9. Theo Bestebroer
10. Nicholas C Wu
11. Bart L Haagmans

• Curated by eLife

  Evaluation Summary:

  This manuscript follows up on work documenting the relevance of the multi-basic cleavage site (MBCS) in the spike (S) protein of SARS-CoV-2 for determining cell tropism and mode of cell entry. The paper describes a number of important findings: 1) That SARS-CoV-2 grown in Vero cells rapidly acquires MBCS mutations, where as virus grown in airway epithelial cells or Vero-TMPRSSR2 cells do not; 2) that deep sequencing is necessary to see mutations emerging that are not apparent in consensus sequence reads; 3) that factors such as fetal calf serum can influence the selection of mutant phenotypes, and 4) that cultures derived from differentiated stem cells can provide reproducible systems for virus culture. Together, the work sets out clear guidelines for the propagation of SARS-CoV-2 to avoid adaptations to laboratory cell-lines/conditions and maintain the authenticity of clinical isolates. The work has relevance to other viruses and the use of permissive transformed cell lines.

  (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, ScreenIT

Cdc4 phospho-degrons allow differential regulation of Ame1CENP-U protein stability across the cell cycle

1. Miriam Böhm
2. Kerstin Killinger
3. Alexander Dudziak
4. Pradeep Pant
5. Karolin Jänen
6. Simone Hohoff
7. Karl Mechtler
8. Mihkel Örd
9. Mart Loog
10. Elsa Sanchez-Garcia
11. Stefan Westermann

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to those in the fields of chromosome biology, mitotic regulation, and proteostasis. The authors put forward an interesting model of phosphodegron regulation of kinetochore assembly based on convincing genetic and biochemical data. The novel model will require some additional evidence before it can be considered well-supported, but the paper represents an advance in our knowledge of kinetochore regulation with experiments that are rigorous, well-designed and carefully conducted.

  (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

AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa

1. Yunlu Xue
2. Sean K Wang
3. Parimal Rana
4. Emma R West
5. Christin M Hong
6. Helian Feng
7. David M Wu
8. Constance L Cepko

• Curated by eLife

  Evaluation Summary:

  This authors used AAV in mouse retinas to express several candidate genes that they thought might have favorable effects on cone metabolism and therefore make cones more robust to stress caused by genetic deficiencies. Txnip is the most effective at prolonging cones survival and a combo of HK and PFK is the most effective at shortening cone survival. The investigators evaluated effects of specific mutations in Txnip with known biochemical effects. Their general conclusion is that Txnip may be enhancing mitochondrial function and ATP production and it may allow cones to use alternative fuels more effectively. This is an interesting and informative set of findings and it is presented and discussed in the context of what currently is known about retina metabolism and its influences on photoreceptor survival.

  (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.)

Reviewed by eLife

Sensitivity of ID NOW and RT–PCR for detection of SARS-CoV-2 in an ambulatory population

1. Yuan-Po Tu
2. Jameel Iqbal
3. Timothy O'Leary

• Curated by eLife

  Evaluation Summary:

  The authors evaluate the performance of the Abbott ID NOW SARS-CoV-2 test in a group of non-hospitalized individuals being tested for COVID-19 and compared that performance to an RT-PCR test. The authors also provide an interesting review and meta-analysis of ID NOW performance across the literature. The cohort assessed in this study, however, was small and localized, which currently undermines its comparison with the known performance of the test in broader applications.

  (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, ScreenIT

Modeling spinal locomotor circuits for movements in developing zebrafish

1. Yann Roussel
2. Stephanie F Gaudreau
3. Emily R Kacer
4. Mohini Sengupta
5. Tuan V Bui

• Curated by eLife

  Evaluation Summary:

  In this manuscript, Roussel et al., build models of spinal networks capable of generating coiling and swimming behaviors of embryonic and larval zebrafish. The models use details obtained from earlier experimental studies and insert novel network elements, thus providing testable ideas for rhythm generation. The study will be of high value to those interested in motor pattern generation in general and zebrafish spinal cord function in specific.

  (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

Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption

1. Cheng-Chia Tang
2. Christian D Castro Andrade
3. Maureen J O'Meara
4. Sung-Hee Yoon
5. Tadatoshi Sato
6. Daniel J Brooks
7. Mary L Bouxsein
8. Janaina da Silva Martins
9. Jinhua Wang
10. Nathanael S Gray
11. Barbara Misof
12. Paul Roschger
13. Stephane Blouin
14. Klaus Klaushofer
15. Annegreet Velduis-Vlug
16. Yosta Vegting
17. Clifford J Rosen
18. Daniel O'Connell
19. Thomas B Sundberg
20. Ramnik J Xavier
21. Peter Ung
22. Avner Schlessinger
23. Henry M Kronenberg
24. Rebecca Berdeaux
25. Marc Foretz
26. Marc N Wein

• Curated by eLife

  Evaluation Summary:

  This is a very interesting, novel and informative study. The effects of the inhibitor on CSF1R inhibition are convincing and provide a compelling explanation for the net effects of the compound on the skeleton. The study opens the way for another possible oral therapeutic for osteoporosis.

  (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

GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells

1. Rafael Jesus Fernandez
2. Zachary JG Gardner
3. Katherine J Slovik
4. Derek C Liberti
5. Katrina N Estep
6. Wenli Yang
7. Qijun Chen
8. Garrett T Santini
9. Javier V Perez
10. Sarah Root
11. Ranvir Bhatia
12. John W Tobias
13. Apoorva Babu
14. Michael P Morley
15. David B Frank
16. Edward E Morrisey
17. Christopher J Lengner
18. F Brad Johnson

• Curated by eLife

  Summary: The investigators' study of human AT2 cells-derived from induced pluripotent stem cells (iAT2 cells) in the presence and absence of a known dyskeratosis congenita (DC) pathogenic variant provides an exceptional model for understanding pathogenesis of pulmonary fibrosis in dyskeratosis congenita (DC) and related telomere biology disorders (TBDs). They provide convincing data demonstrating altered WNT signaling in iAT2 cells with short, dysfunctional telomeres and improved growth of iAT2 cells by GSK3 inhibition but fall short of convincingly showing the latter is due restored telomere end protection. The work should be of interest to those in the fields of telomere biology and the TBDs, lung physiology, WNT signaling and stem cell biology.

Reviewed by eLife

Global epistasis emerges from a generic model of a complex trait

1. Gautam Reddy
2. Michael M Desai

• Curated by eLife

  Evaluation Summary:

  The authors consider Darwinian evolution for large systems, with a main focus on how adaptation changes over time. Frequently observed patterns of declining adaptability for a population in a new environment are discussed, i.e., that fitness tends to increase fast initially and then at a slower rate. Another topic is historical contingency in adaptation. A condition for minimal contingency is provided, and a new model (the connectedness model, or CN model) is introduced accordingly. The manuscript is innovative, conceptually interesting, and provides quantitative precision beyond most related studies in the field. However, the presentation currently does not work well for a general audience.

  (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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception

1. Shu Yang
2. Ya Zhang
3. Chuxuan Yang
4. Xuefeng Wu
5. Sarah Maria El Oud
6. Rongfang Chen
7. Xudong Cai
8. Xufeng S Wu
9. Ganhui Lan
10. Xiaoyan Zheng

• Curated by eLife

  Evaluation Summary:

  This is a well-conceived and well-presented study that sheds light on two critical questions related to Hedgehog signaling, namely, the dual function of the Hedgehog co-receptor Ihog in Hh signal transduction and homophilic adhesion, and the regulation of cytoneme structure.

  (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

A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis

1. Jia Li
2. Xuan Qin
3. Jie Shi
4. Xiaoshuang Wang
5. Tong Li
6. Mengyao Xu
7. Xiaosu Chen
8. Yujia Zhao
9. Jiahao Han
10. Yongjun Piao
11. Wenwen Zhang
12. Pengpeng Qu
13. Longlong Wang
14. Rong Xiang
15. Yi Shi

• Curated by eLife

  Evaluation Summary:

  The authors studied ovarian carcinoma and identified a potential role of interleukin 20 receptor subunit alpha (IL20RA) and of IL-20 in regulating the transcoelomic metastasis of ovarian carcinoma, where IL-20 signaling in tumors is protective. This leads to the production of IL-18 and an M1 macrophage phenotype, with reduction of metastasis. The study is of interest to investigators in the area of cancer and cytokines and has potential therapeutic ramifications.

  (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