Evaluated articles

The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

1. Katalin Skrapits
2. Miklós Sárvári
3. Imre Farkas
4. Balázs Göcz
5. Szabolcs Takács
6. Éva Rumpler
7. Viktória Váczi
8. Csaba Vastagh
9. Gergely Rácz
10. András Matolcsy
11. Norbert Solymosi
12. Szilárd Póliska
13. Blanka Tóth
14. Ferenc Erdélyi
15. Gábor Szabó
16. Michael D Culler
17. Cecile Allet
18. Ludovica Cotellessa
19. Vincent Prévot
20. Paolo Giacobini
21. Erik Hrabovszky

• Curated by eLife

  Evaluation Summary:

  This multifaceted study focuses on neurons in the brain that produce a small peptide molecule known as GnRH, which is central to reproduction in its role as the releasing hormone for gonadotropins from the anterior pituitary. The findings will be of interest to scientists interested in the role of neuropeptides in determining normal brain function and the onset of neurodegenerative disorders. The authors provide a detailed anatomical and molecular characterization of a large, previously unnoticed population of GnRH neurons, located in basal ganglia (mainly putamen) in humans, which diverge from the population of GnRH neurons regulating the pituitary, in number (much larger), morphology and, possibly, origin (not from olfactory placode). Moreover, the study rekindles the idea that GnRH producing neurons in other regions of the brain outside the hypothalamus may be involved in neural processes unrelated to reproduction such as locomotion and decision making.

  (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

Locating macromolecular assemblies in cells by 2D template matching with cisTEM

1. Bronwyn A Lucas
2. Benjamin A Himes
3. Liang Xue
4. Timothy Grant
5. Julia Mahamid
6. Nikolaus Grigorieff

• Curated by eLife

  Evaluation Summary:

  Lucas, Himes et al. present multiple practical improvements to the 2D high-resolution template-matching (2DTM) routine for cryo-EM images originally described by Rickgauer et al., eLife 2017. GPU-acceleration and integration into cisTEM make the approach substantially faster and easier to use than the previous CPU-based Matlab implementation. The strengths and weaknesses of the 2DTM are clearly presented and the comparison with 3DTM is thorough. At present the 2DTM approach is likely only suitable for analysis of large assemblies (e.g., ribosomes, proteasomes,etc.) in situ, but future improvements in microscope hardware and the 2DTM routine itself will likely allow application of this approach to smaller complexes.

  (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

Fine-tuned repression of Drp1-driven mitochondrial fission primes a ‘stem/progenitor-like state’ to support neoplastic transformation

1. Brian Spurlock
2. Danitra Parker
3. Malay Kumar Basu
4. Anita Hjelmeland
5. Sajina GC
6. Shanrun Liu
7. Gene P Siegal
8. Alan Gunter
9. Aida Moran
10. Kasturi Mitra

• Curated by eLife

  Evaluation Summary:

  This paper is of interest for cell biologists studying mitochondrial fission as well as stem cell biologists studying neoplastic transformation. The work helps to clarify how variable levels of the master regulator of mitochondrial fission can have substantially different effects on gene regulation and mitochondrial network properties. A combination of complementary methods is used to support the key findings although aspects of data analysis and quantification 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Tracking excess mortality across countries during the COVID-19 pandemic with the World Mortality Dataset

1. Ariel Karlinsky
2. Dmitry Kobak

• Curated by eLife

  Evaluation Summary:

  This is an important and timely manuscript looking at excess mortality across 89 countries and territories over the course of the COVID-19 pandemic. This manuscript will be of interest to demographers and epidemiologists, and also more broadly to the public health community.

  (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, ScreenIT

The photosensitive phase acts as a sensitive window for seasonal multisensory neuroplasticity in male and female starlings

1. Jasmien Orije
2. Emilie Cardon
3. Julie Hamaide
4. Elisabeth Jonckers
5. Veerle M. Darras
6. Marleen Verhoye
7. Annemie Van der Linden

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to a diverse range of scientist as the questions span animal behavior, neuroscience and sex differences in brain-behavior relations. The study used non-invasive brain imaging to track large changes in structures involved in controlling communication between brain regions. The data reveal exciting sex-specific changes in key brain regions involved in learning and memory. The study is well designed, and the key claims of the manuscript appear to be well supported by the data. The imaging approaches employed are thoughtful and rigorous.

  (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

Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells

1. Isobel C Mouat
2. Zachary J Morse
3. Iryna Shanina
4. Kelly L Brown
5. Marc S Horwitz

• Curated by eLife

  Evaluation Summary:

  This study could help shed light on mechanistic connections between latent infection by EBV with an age-dependent autoimmune condition, such as rheumatoid arthritis. The authors use two models: a murine model of rheumatoid arthritis (CIA), and a murine analog of human EBV: 𝜸HV68. The use of these two models allows the investigation of how latent viral infection exacerbates the autoimmune condition via the action of a special class of B cells: Age-associated B cells.

  (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

A transient postnatal quiescent period precedes emergence of mature cortical dynamics

1. Soledad Domínguez
2. Liang Ma
3. Han Yu
4. Gabrielle Pouchelon
5. Christian Mayer
6. George D Spyropoulos
7. Claudia Cea
8. György Buzsáki
9. Gordon Fishell
10. Dion Khodagholy
11. Jennifer N Gelinas

• Curated by eLife

  Evaluation Summary:

  The authors use dense electrode recordings in young mice and EEG recordings in human infants to quantitatively describe the transition from immature patterns of brain activity in sleep to more mature patterns. Interestingly, they find an intervening period when overall activity declines in both species. This study is interesting because it enriches our relatively impoverished view of how mature activity patterns emerge during development. However, reviewers expressed concerns that further work was need to rule out potential artifacts of the surgical and recording techniques used in the animal experiments.

  (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

Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats

1. Carlos G Moreira
2. Christian R Baumann
3. Maurizio Scandella
4. Sergio I Nemirovsky
5. Sven Leach
6. Reto Huber
7. Daniela Noain

• Curated by eLife

  Evaluation Summary:

  This manuscript describes their phase-targeted closed-loop auditory stimulation protocol to alter slow wave oscillations in rodents. This manuscript provides a set of proof-of-concept data for a rodent model of closed-loop auditory stimulation during sleep as a method for augmenting NREM sleep thalamocortical oscillations and its behavioral effect on a motor task. The strongest contribution of this study to the field is that it provides a technical basis for future studies to be carried out which actually explore the neurobiological underpinnings of CLAS in detail. Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent memory). It's also nice to have a non-invasive way to manipulate sleep, particularly to translate rodent research to clinical 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Phosphoproteomics of ATR signaling in mouse testes

1. Jennie R Sims
2. Vitor M Faça
3. Catalina Pereira
4. Carolline Ascenção
5. William Comstock
6. Jumana Badar
7. Gerardo A Arroyo-Martinez
8. Raimundo Freire
9. Paula E Cohen
10. Robert S Weiss
11. Marcus B Smolka

• Curated by eLife

  Evaluation Summary:

  This study describes a phosphoproteomic analysis of the ATR kinase signaling pathway in mouse testis. The study is well designed and performed, the manuscript is properly constructed and written, and the conclusions are supported by the data. The phosphoproteomic data obtained will be very useful resource for the DNA repair, meiosis, and reproductive biology communities studying the roles of the ATR-dependent DNA damage response pathway.

  (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

Relating multivariate shapes to genescapes using phenotype-biological process associations for craniofacial shape

1. Jose D Aponte
2. David C Katz
3. Daniela M Roth
4. Marta Vidal-García
5. Wei Liu
6. Fernando Andrade
7. Charles C Roseman
8. Steven A Murray
9. James Cheverud
10. Daniel Graf
11. Ralph S Marcucio
12. Benedikt Hallgrímsson

• Curated by eLife

  Evaluation Summary:

  This paper offers a new take on multivariate genotype-phenotype mapping that identifies the joint phenotypic effect of genes involved in known biological processes that impact craniofacial variation. More specifically, the work expands on the traditional idea of candidate gene investigations into candidate biological process investigations, grouping multiple genes into a single analysis. In doing so, the authors show the joint effects of three strong candidate processes, chondrocyte differentiation, determination of left/right symmetry, and palate development on multidimensional craniofacial shape in the heterogenous Diversity Outbred mouse population.

  (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

Exosome component 1 cleaves single-stranded DNA and sensitizes human kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor

1. Qiaoling Liu
2. Qi Xiao
3. Zhen Sun
4. Bo Wang
5. Lina Wang
6. Na Wang
7. Kai Wang
8. Chengli Song
9. Qingkai Yang

• Curated by eLife

  Evaluation Summary:

  Targeting DNA repair pathway provides a novel approach managing malignancies and emphasizing the necessity of discovering biomarkers which could select patients who will benefit. In this research the authors performed comprehensive bioinformatic analysis and identified EXOSC1 as the endogenous source of mutation, which was then validated for its role in damaging DNA and could sensitize kidney renal clear cell carcinoma cells to DNA repair inhibitor. This research is innovative for proposing EXOSC1 role in mutagenesis and could serve as the biomarker to discriminate potential patients who would benefit from DNA repair inhibitor treatment.

  (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

Novel neuroanatomical integration and scaling define avian brain shape evolution and development

1. Akinobu Watanabe
2. Amy M Balanoff
3. Paul M Gignac
4. M Eugenia L Gold
5. Mark A Norell

• Curated by eLife

  Evaluation Summary:

  Watanabe and colleagues analyse endocasts from extant (and some fossil) material to identify the distinct evolutionary and developmental patterns governing the growth and scaling relationships found in avian brains. The use of sophisticated geometric morphometrics, high-quality digital endocasts, and a suite of multivariate statistical tests robustly support the findings asserted in the paper, namely that crown birds exhibit a distinct allometric relationship that dictates their brain evolution and development. This paper is of broad interest to those working in comparative and evolutionary neuroanatomy as well as vertebrate paleontology.

  (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

MBNL1 and RBFOX1 co-regulate alternative splicing events transcriptome-wide through a conserved buffering mechanism

1. Melissa Hale
2. Joseph Ellis
3. Ryan Meng
4. Sunny McDaniel
5. Amy Mahady
6. Stacey Wagner
7. Jared Richardson
8. Ona McConnell
9. Eric Wang
10. J. Andrew Berglund

• Curated by eLife

  Evaluation Summary:

  A major question in the field of alternative splicing regulation is how information from multiple, independently-acting splicing factors is integrated into a single signal that informs the spliceosome to include or skip an exon. This study addresses the extent of co-regulation of alternative splicing events by the two RNA binding proteins RBFOX1 and MBNL1. The work has implications for how the effects of perturbing one splicing factor can be buffered by the action of a second RNA binding protein, with broad relevance in development and disease. Additional work would provide more support for a generalized mechanism underlying regulation alternative splicing events.

  (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

Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia

1. Anne-Claire Godet
2. Emilie Roussel
3. Florian David
4. Fransky Hantelys
5. Florent Morfoisse
6. Joffrey Alves
7. Françoise Pujol
8. Isabelle Ader
9. Edouard Bertrand
10. Odile Burlet-Schiltz
11. Carine Froment
12. Anthony K Henras
13. Patrice Vitali
14. Eric Lacazette
15. Florence Tatin
16. Barbara Garmy-Susini
17. Anne-Catherine Prats

• Curated by eLife

  Evaluation Summary:

  This study reports a novel link by which specific cellular mRNAs, that contain internal ribosome sites (IRES), are made competent for translation in paraspeckles in the nucleus. The data showed that a long noncoding RNA, Neat1, is the major player to add transacting factors to the internal ribosome entry site located in fibroblast growth factor 1 mRNAs in the nucleus. This event occurs during hypoxia in mouse cardiomyocytes and is, thus, relevant to gene expression during angiogenesis.

  (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

Analysis of the PcrA-RNA polymerase complex reveals a helicase interaction motif and a role for PcrA/UvrD helicase in the suppression of R-loops

1. Inigo Urrutia-Irazabal
2. James R Ault
3. Frank Sobott
4. Nigel J Savery
5. Mark S Dillingham

• Curated by eLife

  Evaluation Summary:
  The resolution of R-loops that form during collisions between replication and transcription machineries is crucial for cell survival. This is exemplified by the lethality of deletion of PcrA, a helicase that appears to be involved in the resolution of such collisions. Here, the authors aim to characterize the critical regions of PcrA/RNAP interactions and determine the function of such interactions. The manuscript's structural work is refined, elegant and leaves little room for doubt concerning the importance of the CTD PcrA-RNAP molecular interactions. This work moves the field forward in a meaningful way and unravels key aspects of PcrA/UvrD function with regards to interaction and function on RNAP. It will be of interest across the wide field of protein-DNA interactions, both prokaryotic and eukaryotic.

  (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

SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway

1. Shahanshah Khan
2. Mahnoush S Shafiei
3. Christopher Longoria
4. John W Schoggins
5. Rashmin C Savani
6. Hasan Zaki

• Curated by eLife

  Evaluation Summary:

  The identification of a novel role of the spike protein expressed on SARS-CoV-2 in directly evoking the host inflammatory responses has a substantial impact in understanding the molecular mechanism of COVID-19 pathogenesis, which may have implication for development of new therapeutics. The elegant analytic approach conducted herein justifies the major conclusions of this work though several additional steps can be made to validate these claims.

  (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

Genetic variant in 3’ untranslated region of the mouse pycard gene regulates inflammasome activity

1. Brian Ritchey
2. Qimin Hai
3. Juying Han
4. John Barnard
5. Jonathan D Smith

• Curated by eLife

  Evaluation Summary:

  Genetic differences in outbred species such as humans and differences in the epigenomic structure form the basis of the large variability in the immune response. This work demonstrates that a single nucleotide change in the gene encoding for the universal inflammasome adaptor protein ASC regulates mRNA stability of Pycard and thereby inflammasome function. A particular strength of the work is that the authors managed to show, using genetic alterations, that a single SNP in the Pycard gene sequence (rs33183533) between AKR and DBA/2 mice causes variation in inflammasome activity. Given the relevance of inflammasome for various human pathologies, this work is important for a broad readership.

  (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

Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes

1. Sai Srinivas Panapakkam Giridharan
2. Guangming Luo
3. Pilar Rivero-Rios
4. Noah Steinfeld
5. Helene Tronchere
6. Amika Singla
7. Ezra Burstein
8. Daniel D Billadeau
9. Michael A Sutton
10. Lois S Weisman

• Curated by eLife

  Evaluation Summary:

  The authors investigate the role of the PI3P 5-kinase protein (PIKfyve) in endosome to cell surface recycling. They report that PIKfyve function is necessary for cell migration and endsomal recycling of integrin proteins via the SNX17-Retriever pathway. The findings will be of interest to the endosomal research community.

  (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

Cooperation among c-subunits of FoF1-ATP synthase in rotation-coupled proton translocation

1. Noriyo Mitome
2. Shintaroh Kubo
3. Sumie Ohta
4. Hikaru Takashima
5. Yuto Shigefuji
6. Toru Niina
7. Shoji Takada

• Curated by eLife

  Evaluation Summary:

  This is an interesting manuscript describing for the first time experimentally the cooperative effects of mutations to individual key Glu residues in the c-ring of ATP synthase. The main result is that mutations in nearby c subunits are less inhibitory than those in subunits further apart in the ring. This is explained on the basis of MD/MC simulations as a shared waiting time for delayed proton uptake in case of neighboring subunits, which appears logical. Overall the manuscript is well presented, but with some caveats. The works will be of interest to specialists in bioenergetics, and to a wider biochemical, biophysical and structural biology 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. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Slow oscillation–spindle coupling strength predicts real-life gross-motor learning in adolescents and adults

1. Michael A Hahn
2. Kathrin Bothe
3. Dominik Heib
4. Manuel Schabus
5. Randolph F Helfrich
6. Kerstin Hoedlmoser

Reviewed by eLife