Physiology

Ca2+ inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM

1. Ashok R Nayak
2. Montserrat Samsó

• Curated by eLife

  Evaluation Summary:

  Inactivation of ryanodine receptors (RyR1) is an important physiologic phenomenon disruption of which leads to skeletal muscle and heart diseases. By comparing cryoEM structures of RyR1 in closed, open, and inactivated states, this study provides structural insights into RyR1 calcium-dependent inactivation (CDI). The results rationalize how some disease-causing mutations in RyR1 eliminate CDI of the channel. The study will be of interest to ion channel structural biologists and physiologists studying skeletal muscle pathologies.

  (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 plasma membrane-localized polycystin-1/polycystin-2 complex in endothelial cells elicits vasodilation

1. Charles E MacKay
2. Miranda Floen
3. M Dennis Leo
4. Raquibul Hasan
5. Tessa AC Garrud
6. Carlos Fernández-Peña
7. Purnima Singh
8. Kafait U Malik
9. Jonathan H Jaggar

• Curated by eLife

  Evaluation Summary:

  This study is potentially of high significance to a broad audience of scientists working on vascular reactivity and the role of ion channels in controlling endothelial cell signaling and vessel contractility. The study uses novel Endothelial cell specific knockout mice of Polycystin-1 and 2 (PC1 and PC2) proteins to show the requirement of PC1 and PC2 in flow-mediated vasodilation, how PC-1 and PC-2 interact and that their functions are interdependent. The findings from this study are novel and significant. The animal models used in this study are state of the art and the data overall are of high quality. However, additional data are needed to support the conclusions of the study. Further, additional controls and clarifications are required.

  (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

Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock

1. Eva Kaulich
2. Trae Carroll
3. Brian D Ackley
4. Yi-Quan Tang
5. Iris Hardege
6. Keith Nehrke
7. William R Schafer
8. Denise S Walker

• Curated by eLife

  Evaluation Summary:

  This study investigates the role of acid sensing channels in pH homeostasis required for normal rhythmic muscle contractions in the defecation cycle of C .elegans. It is of importance to scientists with interest in ASIC channel function, pH homeostasis and the cellular mechanisms underlying generation of ultradian rhythms.

  (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

Impacts of the COVID-19 pandemic on a human research islet program

1. Tina J. Dafoe
2. Theodore Dos Santos
3. Aliya F. Spigelman
4. James Lyon
5. Nancy Smith
6. Austin Bautista
7. Patrick E. MacDonald
8. Jocelyn E. Manning Fox

Reviewed by ScreenIT

The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle

1. Xueyong Wang
2. Murad Nawaz
3. Chris DuPont
4. Jessica H Myers
5. Steve RA Burke
6. Roger A Bannister
7. Brent D Foy
8. Andrew A Voss
9. Mark M Rich

• Curated by eLife

  Evaluation Summary:

  This addresses an important area of excitation contraction coupling failure of potential clinical translational importance. They report that progressive depolarization of the resting potential upon excitation contraction coupling results in a persistence of action potential generation in the face of a failure of Ca2+ release.

  (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

Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure

1. Erminia Donnarumma
2. Michael Kohlhaas
3. Elodie Vimont
4. Etienne Kornobis
5. Thibault Chaze
6. Quentin Giai Gianetto
7. Mariette Matondo
8. Maryse Moya-Nilges
9. Christoph Maack
10. Timothy Wai

Reviewed by Review Commons

Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors

1. Alexis Ruiz
2. Sofia Benucci
3. Urs Duthaler
4. Christoph Bachmann
5. Martina Franchini
6. Faiza Noreen
7. Laura Pietrangelo
8. Feliciano Protasi
9. Susan Treves
10. Francesco Zorzato

• Curated by eLife

  Evaluation Summary:

  The paper describes improvement in muscle phenotype of a congenital myopathy mouse model by a combined treatment with pharmacological inhibitors of Class IIa histone deacetylases and DNA methylases. The paper demonstrates in principle that there are treatment avenues to pursue but their application could be limited as phenotypic rescue appears to be restricted to particular muscle fiber types.

  (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

High-intensity interval training remodels the proteome and acetylome of human skeletal muscle

1. Morten Hostrup
2. Anders Krogh Lemminger
3. Ben Stocks
4. Alba Gonzalez-Franquesa
5. Jeppe Kjærgaard Larsen
6. Julia Prats Quesada
7. Martin Thomassen
8. Brian Tate Weinert
9. Jens Bangsbo
10. Atul Shahaji Deshmukh

• Curated by eLife

  Evaluation Summary

  This paper will be of interest to readers in the fields of exercise physiology, muscle biology and energy metabolism. The authors provide a proteomic resource where changes in the skeletal muscle proteome and acetyl-proteome have been assessed following the increasingly popular exercise intervention of high intensity interval training (HIIT). The adaptive responses reported provide new insight into the metabolic, contractile and transcriptional changes in muscle, and may represent an excellent resource for stimulating future focussed molecular studies 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. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit

1. Brogan Ashley
2. Claire Simner
3. Antigoni Manousopoulou
4. Carl Jenkinson
5. Felicity Hey
6. Jennifer M Frost
7. Faisal I Rezwan
8. Cory H White
9. Emma M Lofthouse
10. Emily Hyde
11. Laura DF Cooke
12. Sheila Barton
13. Pamela Mahon
14. Elizabeth M Curtis
15. Rebecca J Moon
16. Sarah R Crozier
17. Hazel M Inskip
18. Keith M Godfrey
19. John W Holloway
20. Cyrus Cooper
21. Kerry S Jones
22. Rohan M Lewis
23. Martin Hewison
24. Spiros DD Garbis
25. Miguel R Branco
26. Nicholas C Harvey
27. Jane K Cleal

• Curated by eLife

  Evaluation Summary:

  This manuscript uses primary placental units and villous explants to examine the placental metabolism of vitamin D and effects of vitamin D on placental gene expression. The studies demonstrate that the placenta actively transports 25D, such that the fetal levels are dependent on placental function rather than simple diffusion from the maternal circulation. Furthermore, they demonstrate actions of vitamin D on placental gene expression. This paper should be of interest to cell biologists and obstetricians/gynaecologists studying the role of the placenta in fetal growth and development.

  (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

SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization

1. Pinxiu Huang
2. Wenbo Deng
3. Haili Bao
4. Zhong Lin
5. Mengying Liu
6. Jinxiang Wu
7. Xiaobo Zhou
8. Manting Qiao
9. Yihua Yang
10. Han Cai
11. Faiza Rao
12. Jingsi Chen
13. Dunjin Chen
14. Jinhua Lu
15. Haibin Wang
16. Aiping Qin
17. Shuangbo Kong

• Curated by eLife

  Evaluation Summary:

  Huang et al have identified SOX4 as a key regulatory factor that controls prolactin and FOXO1 transcription factor which in turn regulate decidualization, an important process in embryo development. Further, they have identified that SOX4 also regulates progesterone receptor and dysregulated SOX4-progesterone and ubiquitin ligase HERC4can lead to embryo implantation failure thus explaining the molecular basis of recurrent implantation failure in humans. Overall the study is interesting and the data are very strong. Some concerns noted were the use of immortalized stromal cells, and incomplete nature of studies with human endometrial stroll cells from endometriosis patients, and lack of sufficient discussion in some parts of the text, and whether specific progesterone isofoms are involved downstream of SOX4.

  (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