Physiology

Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation

1. Phoebe M Kirkwood
2. Douglas A Gibson
3. Isaac Shaw
4. Ross Dobie
5. Olympia Kelepouri
6. Neil C Henderson
7. Philippa TK Saunders

• Curated by eLife

  Evaluation Summary:

  This is an important and delicately designed study that uses integrated tools to reveal underlying mechanisms of repair of the endometrium at menstruation. It combines single cell sequencing analysis and lineage tracing technologies to strongly prove that repair-specific cells originate from the fibroblast cell clusters and PDGFRα+ endometrial fibroblasts undergo MET and can become incorporated into the luminal epithelium of the post repair tissue.

  (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 name with the authors.)

Reviewed by eLife

Hepatic inactivation of murine Surf4 results in marked reduction in plasma cholesterol

1. Vi T Tang
2. Joseph McCormick
3. Bolin Xu
4. Yawei Wang
5. Huan Fang
6. Xiao Wang
7. David Siemieniak
8. Rami Khoriaty
9. Brian T Emmer
10. Xiao-Wei Chen
11. David Ginsburg

• Curated by eLife

  Evaluation Summary:

  By the use of liver specific gene knock-out approaches Tang et al have clearly documented an important role for an endoplasmic reticulum sorting receptor, SURF4, in the efficient secretion of PCSK9, a protein in circulation that binds to and enhances the intracellular uptake and degradation of the low density lipoprotein receptor. As a consequence of liver specific knock-outs, adult mice survive well with an exceptionally lower level of circulating cholesterol, triglycerides and various lipoproteins. These compelling results reinforce the prospect for the development of therapeutic approaches in cholesterol and LDL reduction by targeting the intracellular association of PCSK9 and the SURF4 receptor. The work is elegant and complete with the only concern that some of the work and results overlap work published previously by some of these authors.

  (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 name with the authors.)

Reviewed by eLife

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

1. Karla J Suchacki
2. Benjamin J Thomas
3. Yoshiko M Ikushima
4. Kuan-Chan Chen
5. Claire Fyfe
6. Adriana AS Tavares
7. Richard J Sulston
8. Andrea Lovdel
9. Holly J Woodward
10. Xuan Han
11. Domenico Mattiucci
12. Eleanor J Brain
13. Carlos J Alcaide-Corral
14. Hiroshi Kobayashi
15. Gillian A Gray
16. Phillip D Whitfield
17. Roland H Stimson
18. Nicholas M Morton
19. Alexandra M Johnstone
20. William P Cawthorn

Reviewed by Review Commons

Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide

1. Thao DV Le
2. Dianxin Liu
3. Gai-Linn K Besing
4. Ritika Raghavan
5. Blair J Ellis
6. Ryan P Ceddia
7. Sheila Collins
8. Julio E Ayala

• Curated by eLife

  Evaluation Summary:

  This manuscript examines the importance of PKA-dependent mTORC1 activation for the weight-loss effects of liraglutide. The work has the potential to provide important insights, but at present is deemed preliminary as it lacks details on the mouse model and control data and needs a more in-depth analysis of the metabolic phenotype.

  (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 name with the authors.)

Reviewed by eLife

A remarkable adaptive paradigm of heart performance and protection emerges in response to marked cardiac-specific overexpression of ADCY8

1. Kirill V Tarasov
2. Khalid Chakir
3. Daniel R Riordon
4. Alexey E Lyashkov
5. Ismayil Ahmet
6. Maria Grazia Perino
7. Allwin Jennifa Silvester
8. Jing Zhang
9. Mingyi Wang
10. Yevgeniya O Lukyanenko
11. Jia-Hua Qu
12. Miguel Calvo-Rubio Barrera
13. Magdalena Juhaszova
14. Yelena S Tarasova
15. Bruce Ziman
16. Richard Telljohann
17. Vikas Kumar
18. Mark Ranek
19. John Lammons
20. Rostislav Bychkov
21. Rafael de Cabo
22. Seungho Jun
23. Gizem Keceli
24. Ashish Gupta
25. Dongmei Yang
26. Miguel A Aon
27. Luigi Adamo
28. Christopher H Morrell
29. Walter Otu
30. Cameron Carroll
31. Shane Chambers
32. Nazareno Paolocci
33. Thanh Huynh
34. Karel Pacak
35. Robert Weiss
36. Loren Field
37. Steven J Sollott
38. Edward G Lakatta

• Curated by eLife

  Evaluation Summary:

  The study is overall well-planned and the amount of data presented by the authors is impressive. The work nicely incorporates animal-level physiology (echocardiography data), tests for known canonical markers of hypertrophy, and then delves into an unbiased analysis of the transcriptome and proteome of LV tissue in bulk. The techniques and analyses in the study are adequately executed and within the realm of expertise of the Lakatta laboratory. This study is a necessary and crucial first step to extensively phenotype this mouse line and generate hypotheses for further 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 #1 agreed to share their name with the authors.)

Reviewed by eLife

Machine learning-assisted fluoroscopy of bladder function in awake mice

1. Helene De Bruyn
2. Nikky Corthout
3. Sebastian Munck
4. Wouter Everaerts
5. Thomas Voets

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to researchers working in the area of lower urinary tract dysfunction. It describes a novel method to reliably study bladder function; the approach allows for monitoring bladder filling and emptying in freely moving, non-anaesthetized animals without the need for catheter implantation. This work has optimized a machine learning algorithm for defining the outline of the urinary bladder border from fluoroscopic images of mice that received subcutaneous injections of iodinated radiocontrast media. The advantage is that with images taken at 30 images/second and with monitoring bladder dynamics requiring hours-long observation periods, this very large number of generated images no longer requires manual analysis.

  (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 skeletal muscle circadian clock regulates titin splicing through RBM20

1. Lance A Riley
2. Xiping Zhang
3. Collin M Douglas
4. Joseph M Mijares
5. David W Hammers
6. Christopher A Wolff
7. Neil B Wood
8. Hailey R Olafson
9. Ping Du
10. Siegfried Labeit
11. Michael J Previs
12. Eric T Wang
13. Karyn A Esser

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of broad interest to the field of muscle biology, muscle physiology, exercise physiology, metabolism and circadian rhythms. This manuscript identifies a new molecular pathway that connects circadian rhythms to muscle structure and function through titin isoform switching.

  (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

TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons

1. Wendy Wing Sze Yue
2. Lin Yuan
3. Joao M Braz
4. Allan I Basbaum
5. David Julius

• Curated by eLife

  Evaluation Summary:

  The manuscript by Yue et al describes studies investigating the role of sensory neuron versus arteriole expression of Trpv1 in body temperature control. This is a detail about the contribution of different cells which has significance because of the reported on-target side-effect of hyperthermia by Trpv1-antagonists. The study shows that the effects on body temperature are predominantly produced through sensory neurons. From these studies it is speculated that the actions of Trpv1 might be pharmacologically modified to permit dissociation of the effects on neurogenic inflammation and the undesirable effects on body temperature.

  (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. All reviewers agreed to share their names with the authors.)

Reviewed by eLife

Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

1. Amanda E Brandon
2. Lewin Small
3. Tuong-Vi Nguyen
4. Eurwin Suryana
5. Henry Gong
6. Christian Yassmin
7. Sarah E Hancock
8. Tamara Pulpitel
9. Sophie Stonehouse
10. Letisha Prescott
11. Melkam A Kebede
12. Belinda Yau
13. Lake-Ee Quek
14. Greg M Kowalski
15. Clinton R Bruce
16. Nigel Turner
17. Gregory J Cooney

• Curated by eLife

  Evaluation Summary:

  This study evaluates the effects of two distinct dietary methods that cause obesity in mice (high fat vs high starch) on insulin sensitivity and glucose homeostasis. Through a series of nicely performed physiology experiments, the authors demonstrated that high starch feeding causes obesity without deleterious effects on insulin sensitivity. This work will have an impact in the field and help define the important lipid mediators of metabolic 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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation

1. Leonardo Vinicius Monteiro de Assis
2. Lisbeth Harder
3. José Thalles Lacerda
4. Rex Parsons
5. Meike Kaehler
6. Ingolf Cascorbi
7. Inga Nagel
8. Oliver Rawashdeh
9. Jens Mittag
10. Henrik Oster

• Curated by eLife

  Evaluation Summary:

  Monteiro de Assis et al. demonstrate a role for T3 in modulating circadian metabolic rhythms both systemically and within the liver. The findings extend the molecular framework in which organismal metabolism is coordinated in a circadian fashion.

  (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