Physiology

Tenotomy-induced muscle atrophy is sex-specific and independent of NFκB

1. Gretchen A Meyer
2. Stavros Thomopoulos
3. Yousef Abu-Amer
4. Karen C Shen

• Curated by eLife

  eLife assessment

  The purpose of the study was to evaluate the transcription factor NF-kB, a common transcription factor that is thought to mediate muscle atrophy, in the setting of a rotator cuff injury. The authors used gain of function and loss of function NF-kB inhibitors to show that, surprisingly, NF-kB does not seem to be a major mediator of muscle atrophy in this model (as compared to other atrophy models), but there are sex-related differences. They found that male mice were more likely to have atrophy regulated by autophagy, both of which are interesting, novel findings.

Reviewed by eLife

A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice

1. Reem Abdel-Haq
2. Johannes CM Schlachetzki
3. Joseph C Boktor
4. Thaisa M Cantu-Jungles
5. Taren Thron
6. Mengying Zhang
7. John W Bostick
8. Tahmineh Khazaei
9. Sujatha Chilakala
10. Livia H Morais
11. Greg Humphrey
12. Ali Keshavarzian
13. Jonathan E Katz
14. Matthew Thomson
15. Rob Knight
16. Viviana Gradinaru
17. Bruce R Hamaker
18. Christopher K Glass
19. Sarkis K Mazmanian

• Curated by eLife

  eLife assessment

  The complex mechanisms through which diet impact Parkinson's Disease are unclear, limiting the ability to guide patients to an optimal diet. Here, researchers use a mouse model to test the impact of dietary fiber, revealing changes in gut microbes and immune cells in the brain. This study raises intriguing hypotheses about how diet-induced changes in the microbiome could lead to changes in brain function.

Reviewed by eLife

Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel

1. Peter R Strege
2. Luke M Cowan
3. Constanza Alcaino
4. Amelia Mazzone
5. Christopher A Ahern
6. Lorin S Milescu
7. Gianrico Farrugia
8. Arthur Beyder

• Curated by eLife

  eLife Assessment:

  This manuscript presents a biophysical study of the nature of the mechanosensitivity of voltage-gated sodium channels. The identification of a voltage-independent mechanosensitive step is well founded, the proposal that this step is the intracellular gate is plausible speculation. It is expected to be of interest to scientists studying the physical basis of mechanosensitivity in electrophysiology.

  (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

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