Evaluated articles

Targeting circPTPN12/miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis

1. Minmin Song
2. Guangfeng Zhao
3. Haixiang Sun
4. Simin Yao
5. Zhenhua Zhou
6. Peipei Jiang
7. Qianwen Wu
8. Hui Zhu
9. Huiyan Wang
10. Chenyan Dai
11. Jingmei Wang
12. Ruotian Li
13. Yun Cao
14. Haining lv
15. Dan Liu
16. Jianwu Dai
17. Yan Zhou
18. Yali Hu

• Curated by eLife

  Evaluation Summary:

  The study by Song and colleagues explores the role of circRNAs in fibrosis of the endometrium. The paper is of interest for scientists working in the field of endometrial fibrosis and most likely can have implications for other endometrial disorders characterised by fibrotic tissues. The study unravel the molecular mechanism underlying the disease and the thorough experimental part fully support the author's claim.

  (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

Rampant tooth loss across 200 million years of frog evolution

1. Daniel J Paluh
2. Karina Riddell
3. Catherine M Early
4. Maggie M Hantak
5. Gregory FM Jongsma
6. Rachel M Keeffe
7. Fernanda Magalhães Silva
8. Stuart V Nielsen
9. María Camila Vallejo-Pareja
10. Edward L Stanley
11. David C Blackburn

• Curated by eLife

  Evaluation Summary:

  This manuscript will find a broad audience in the fields of evolutionary and developmental biology, especially herpetology, systematics, and those interested in the evolutionary history of vertebrate teeth. The expansive dataset presented by the authors has allowed for rigorous computational analyses yielding new insight into the evolutionary history of teeth in frogs, which is a topic that has received little attention from the scientific community. The resulting data largely support the key claims of the manuscript.

  (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

A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes prostaglandin2α-induced corpus luteum regression

1. Dianrong Li
2. Jie Chen
3. Jia Guo
4. Lin Li
5. Gaihong Cai
6. She Chen
7. Jia Huang
8. Hui Yang
9. Yinhua Zhuang
10. Fengchao Wang
11. Xiaodong Wang

• Curated by eLife

  Evaluation Summary:

  This manuscript is of potential interest to the field of cell death research in terms of understanding basic mechanisms and in the context of disease. The authors have used a broad range of methodologies and identified key phosphorylation sites on the protein kinase RIPK3 that determine whether cells undergo necroptotic or apoptotic cell death. The authors examine this phosphorylation event in the context of corpus luteum regression.

  (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

Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data

1. Oliver Stirrup
2. Joseph Hughes
3. Matthew Parker
4. David G Partridge
5. James G Shepherd
6. James Blackstone
7. Francesc Coll
8. Alexander Keeley
9. Benjamin B Lindsey
10. Aleksandra Marek
11. Christine Peters
12. Joshua B Singer
13. The COVID-19 Genomics UK (COG-UK) consortium
14. Asif Tamuri
15. Thushan I de Silva
16. Emma C Thomson
17. Judith Breuer

• Curated by eLife

  Evaluation Summary:

  The paper describes an algorithm that combines epidemiological and sequence data to provide a rapid assessment of the probability of healthcare-associated infections among hospital onset SARS-CoV-2 infections, that also may be associated with outbreak events. There is an urgent need for tools that can synthesise multiple data streams to provide real time information to healthcare professionals. It is questionable to what extent the tool presented is generalisable to medical facilities outside of the specific data rich settings considered here, or if the tool is useful for prospective analyses. This study would be of interest to specialists working in hospital infection prevention, with more limited further 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 agreed to share their name with the authors.)

Reviewed by eLife, ScreenIT

Glycan-based shaping of the microbiota during primate evolution

1. Sumnima Singh
2. Patricia Bastos-Amador
3. Jessica Ann Thompson
4. Mauro Truglio
5. Bahtiyar Yilmaz
6. Silvia Cardoso
7. Daniel Sobral
8. Miguel P Soares

• Curated by eLife

  Evaluation Summary:

  30 million years ago the ancestors of Old World primates lost the ability to produce alpha-gal due to the fixation of several loss-of-function mutations in the GGTA1 gene. The evolutionary advantage of such loss remains elusive. Here, the authors provide additional insights into the pleiotropic role of ggta1 in shaping the gut microbiota, immune function, susceptibility to sepsis, and eventual fitness advantage.

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

Reviewed by eLife

Differential dopaminergic modulation of spontaneous cortico–subthalamic activity in Parkinson’s disease

1. Abhinav Sharma
2. Diego Vidaurre
3. Jan Vesper
4. Alfons Schnitzler
5. Esther Florin

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to readers in the field of clinical neuroscience and movement disorders. The identification and characterization of dynamic networks that are differentially affected by dopaminergic medication in patients with Parkinson's disease is an important contribution to our understanding of physiologic and pathologic brain activities. The used methods provide the potential to uncover spectral, local, and temporal properties of dynamic neural systems. Overall, the data are properly analyzed, although many aspects of reporting the results could be worked out better.

  (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

An implant for long-term cervical vagus nerve stimulation in mice

1. Ibrahim T. Mughrabi
2. Jordan Hickman
3. Naveen Jayaprakash
4. Eleni S. Papadoyannis
5. Adam Abbas
6. Yao-Chuan Chang
7. Sunhee Lee
8. Timir Datta-Chaudhuri
9. Eric H. Chang
10. Theodoros P. Zanos
11. Robert C. Froemke
12. Cristin Welle
13. Yousef Al-Abed
14. Stavros Zanos

Reviewed by eLife

Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia

1. Jenny I Aguilar
2. Mary Hongying Cheng
3. Josep Font
4. Alexandra C Schwartz
5. Kaitlyn Ledwitch
6. Amanda Duran
7. Samuel J Mabry
8. Andrea N Belovich
9. Yanqi Zhu
10. Angela M Carter
11. Lei Shi
12. Manju A Kurian
13. Cristina Fenollar-Ferrer
14. Jens Meiler
15. Renae Monique Ryan
16. Hassane S Mchaourab
17. Ivet Bahar
18. Heinrich JG Matthies
19. Aurelio Galli

• Curated by eLife

  Evaluation Summary:

  Infantile parkinsonism-dystonia is a rare but devastating condition that leads to early mortality. Mutations in the dopamine transporter that decrease its transport activity or cell surface expression have been identified as potential causes of this disease. Here, Aguilar et al perform a series of experiments to examine the effect of one of the mutations, R445C, on properties of the transporter in cell culture and on motor function in newly generated transgenic flies. They also explore structure function relationships of the mutation using X-ray crystallography of LeuT, a bacterial homolog, and molecular modeling. Lastly, they show blocking lysosomal degradation rescues a motor deficit in the flies. Insights from the work could lead to new approaches to specifically modulate the transporter structure to restore surface expression and function of the mutant dopamine transporter in this disorder. This elegant and technically sophisticated analysis is of interest to readers in the fields of neurobiology, behavior, and movement disorders, as the work provides an excellent example of using a variety of different approaches to determine the relationship between transporter structure and activity and potentially underlying pathology in 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 agreed to share their name with the authors.)

Reviewed by eLife

Cholinergic signalling in the forebrain controls microglial phenotype and responses to systemic inflammation

1. Arshed Nazmi
2. Eadaoin W. Griffin
3. Robert H. Field
4. Sean Doyle
5. Edel Hennessy
6. Martin O’Donnell
7. Aisling Rehill
8. Anthony McCarthy
9. Daire Healy
10. Michelle M. Doran
11. John P. Lowry
12. Colm Cunningham

• Curated by eLife

  Evaluation Summary:

  Loss or decrease of cholinergic tone occurs during brain aging or in pathologies such as Alzheimer's disease. This elegant study has used in vitro and in vivo approaches to explore the impact of decreased cholinergic signaling on hippocampal/cortical microglial state. The study demonstrates that the neurotransmitter Acetylcholine (ACh) maintain microglial cells in a homeostatic state, preventing their priming towards an activated state that leads to an exacerbated response to an inflammatory stimulus. The study thus provides important insights on the feed-forward contribution of microglial cells to neurodegenerative 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 #2 agreed to share their name with the authors.)

Reviewed by eLife

Probing the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility

1. Zhongwen Chen
2. Dongmyung Oh
3. Kabir Hassan Biswas
4. Ronen Zaidel-Bar
5. Jay T Groves

• Curated by eLife

  Evaluation Summary:

  These data provide in vivo evidence for a previously described kinetic-proofreading mechanism in phase-separated condensates. The strength is being able to compare the impacts of clustering of signaling molecules with a non-clustered control in the same cell. The limitations are that there is not necessarily new biological insight gained and the effects reported are surprisingly modest compared with expectations from reconstituted systems. This paper will be of broad interest to scientists who study membrane-associated cell signaling.

  (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

Myoglobin primary structure reveals multiple convergent transitions to semi-aquatic life in the world's smallest mammalian divers

1. Kai He
2. Triston G Eastman
3. Hannah Czolacz
4. Shuhao Li
5. Akio Shinohara
6. Shin-ichiro Kawada
7. Mark S Springer
8. Michael Berenbrink
9. Kevin L Campbell

• Curated by eLife

  Evaluation Summary:

  This study, based on an elaborated animal sample collection, reconstructs a comprehensive tree of Eulipotyphla, especially concentrating on Talpidae (moles), and infers the transitions of their lifestyles. It also models myoglobin structure and calculate electrophoretic mobility, demonstrating that semiaquatic eulipotyphlans have a higher net surface charge than fossorial, semifossorial, and terrestrial relatives. This variable myoglobin property indicates convergent shifts to a semi-aquatic lifestyle in multiple independent lineages including three separate times by ‘water shrews’, the smallest endothermic divers.

  (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

Agl24 is an ancient archaeal homolog of the eukaryotic N-glycan chitobiose synthesis enzymes

1. Benjamin H Meyer
2. Panagiotis S Adam
3. Ben A Wagstaff
4. George E Kolyfetis
5. Alexander J Probst
6. Sonja V Albers
7. Helge C Dorfmueller

• Curated by eLife

  Evaluation Summary:

  The authors identified the enzyme involved in the transfer of the second GlcNAC residue on the nascent oligosaccharide in protein N-glycosylation of the thermophilic Crenarchaeon Sulfolobus acidocaldarius. Although N-glycosylation is well-known in Euryarchaeota, the enzymes involved in this process, their substrates, and the mechanisms followed to produce the mature glycan are still elusive in Crenarchaeota. This work will impact the community interested in glycoprotein biogenesis and evolution. The experiments reported in this study were well-performed and the results are solid, but text and figure editing is required to enhance the accuracy, readability and strengthen the message of the 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 #2 agreed to share their name with the authors.)

Reviewed by eLife

Evidence accumulation, not ‘self-control’, explains dorsolateral prefrontal activation during normative choice

1. Cendri A Hutcherson
2. Anita Tusche

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to neuroscientists studying decision-making and the frontal lobe. The paper combines computational modeling with brain imaging across several datasets to better understand the role of brain regions previously implicated in self-control during normative behavior (generosity, healthy eating). On balance, the data provide more support for the view that dorsolateral prefrontal cortex is involved in reading out the evidence in favor of different choice alternatives than the view that this region implements control processes that bias choices towards normative goals.

  (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

Early life experience sets hard limits on motor learning as evidenced from artificial arm use

1. Roni O Maimon-Mor
2. Hunter R Schone
3. David Henderson Slater
4. A Aldo Faisal
5. Tamar R Makin

• Curated by eLife

  Evaluation Summary:

  This is a large study of the development of human sensorimotor control using unique populations who have undergone limb loss at different times in their lives.This paper will be of interest to scientists within the field of motor control and for those interested in the development and plasticity of the motor system. An important finding is that reaching performance with an artificial arm is better in people who lost their limb in adulthood and worse in those with congenital limb loss. While the mechanisms underlying this result are not yet clear, it suggests that the benefits of early developmental experience with an intact limb are superior to early experience with an artificial arm.

  (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

Post-translational flavinylation is associated with diverse extracytosolic redox functionalities throughout bacterial life

1. Raphaël Méheust
2. Shuo Huang
3. Rafael Rivera-Lugo
4. Jillian F. Banfield
5. Samuel H. Light

• Curated by eLife

  Evaluation Summary:

  Light and coworkers provide evidence from mining 31,910 prokaryotic genomes for the widespread occurrence of extracytosolic flavinylated FMN-binding domains in bacteria. They discovered extracytosolic flavinylation of five protein classes potentially involved in transmembrane electron transfer. The study also proposes new connections between respiration and iron assimilation and identifies two novel substrates of ApbE enzymes. This work should inspire further work in the fields of redox enzymology and bioenergetics to characterize the suggested involvement of flavinylated protein complexes in prokaryotes.

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

Reviewed by eLife

Contingency and chance erase necessity in the experimental evolution of ancestral proteins

1. Victoria Cochran Xie
2. Jinyue Pu
3. Brian P.H. Metzger
4. Joseph W. Thornton
5. Bryan C. Dickinson

• Curated by eLife

  Evaluation Summary:

  This manuscript, which will be of interest to students of evolution and anybody interested in protein function, uses an original, clever, high throughput, and rapid experimental protein evolution method to assess the roles and contributions of contingency, chance, and necessity in the evolution of protein-protein interactions. The authors focus on the animal BCL-2 protein family and on the evolution of their binding properties to two proteins, NOXA and BID. Using several replicates and several starting points, they found little predictability between replicates of single starting points and among those from multiple starting points, indicating that there is no single pathway through sequence space to the selected function, and that historical contingency is the primary cause of protein evolution here. The presented results convincingly illustrate the potential of this novel technology for future work in directed protein 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 #1 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Differential conditioning produces merged long-term memory in Drosophila

1. Bohan Zhao
2. Jiameng Sun
3. Qian Li
4. Yi Zhong

• Curated by eLife

  Evaluation Summary:

  This work reveals a novel form of Drosophila long-term memory (LTM) that is of potential interest to most neuroscientists working on various animals. While classical protein-synthesis-dependent LTM forms only after repetitive spaced trials of olfactory conditioning, the authors discovered that flies also form a "blurred" or "vague" protein-synthesis-dependent LTM which distinguishes the experienced two odors from the third naive odor after single-trial training. This merged LTM lacking the event details likely occurs in most animals since long-lasting memory of occasional threatening experiences for future escape behavior is crucial for 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. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Allosteric communication in DNA polymerase clamp loaders relies on a critical hydrogen-bonded junction

1. Subu Subramanian
2. Kent Gorday
3. Kendra Marcus
4. Matthew R Orellana
5. Peter Ren
6. Xiao Ran Luo
7. Michael E O'Donnell
8. John Kuriyan

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest not only to scientists working in the primary field of DNA replication, but also to molecular biologists employing deep mutagenesis as well as structural biologists interested in the functions of the broader class of AAA+ ATPase molecular machines. The work examines relationships between protein sequence, structure and function in the bacteriophage T4 clamp-clamp loader complex, a highly studied AAA+ ATPase that deposits ring-shaped proteins onto DNA to support DNA polymerase processivity and DNA replication. The clamp loader system is revealed to have a high tolerance to amino acid substitution, with little correlation between permitted substitutions and phylogenetic variation. A hitherto unrecognized residue in the clamp loader, which appears to be shared among certain AAA+ ATPase members, is identified as critical for the maintenance of a functional structure and for allosteric coupling. The key claims of the paper are well supported by the data presented, and the employed methodology has undergone rigorous validation. Although a few control studies are still needed, this is a novel and significant paper overall.

  (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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Structural Basis for Allosteric Control of the SERCA-Phospholamban Membrane Complex by Ca ²⁺ and cAMP-dependent Phosphorylation

1. Daniel K. Weber
2. Máximo Sanz-Hernández
3. U. Venkateswara Reddy
4. Songlin Wang
5. Erik K. Larsen
6. Tata Gopinath
7. Martin Gustavsson
8. Razvan L. Cornea
9. David D. Thomas
10. Alfonso De Simone
11. Gianluigi Veglia

• Curated by eLife

  Evaluation Summary:

  There are many of membrane-embedded mini-proteins, which fulfill a large range of regulatory functions. One of them is phospholamban, a single transmembrane helix protein that regulates the sarcoplasmic reticulum Ca2+-ATPase by binding in the membrane. The work presented here combines new experiments with computer simulations with the aim of arriving at a more definitive answer to the long-standing mechanistic question of how exactly phosphorylation of phospholamban modulates its regulatory behavior. In this manuscript, an allosteric mechanism is presented, which could be of general importance for the whole family of these mini-proteins.

  (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

Diversity of excitatory release sites

1. Maria Rita Karlocai
2. Judit Heredi
3. Tünde Benedek
4. Noemi Holderith
5. Andrea Lorincz
6. Zoltan Nusser

• Curated by eLife

  Evaluation Summary:

  The authors study how individual synapses can compute information by tuning the properties of the individual components that drive synaptic communication between neurons. Using cutting edge physiology and morphology they show that the reliability of synaptic communication depends not only on how many units drive synaptic communication, but also the authors suggest that individual units vary in their quantitative molecular composition.

  (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