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  1. Glucagon-Like Peptide-1 Receptor Activation Stimulates PKA-Mediated Phosphorylation of Raptor and this Contributes to the Weight Loss Effects of Liraglutide

    This article has 8 authors:
    1. Thao D.V. 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
    This article has been curated by 1 group:
    • 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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  2. A Remarkable Adaptive Paradigm Of Heart Performance And Protection Emerges In Response To The Constitutive Challenge Of Marked Cardiac-Specific Overexpression Of Adenylyl Cyclase Type 8

    This article has 38 authors:
    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 Beshkov
    21. Rafael deCabo
    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 G Weiss
    36. Loren Field
    37. Steven J. Sollott
    38. Edward G Lakatta
    This article has been curated by 1 group:
    • 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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  3. Machine learning-assisted fluoroscopy of bladder function in awake mice

    This article has 5 authors:
    1. Helene De Bruyn
    2. Nikky Corthout
    3. Sebastian Munck
    4. Wouter Everaerts
    5. Thomas Voets
    This article has been curated by 1 group:
    • 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.)

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  4. The Skeletal Muscle Circadian Clock Regulates Titin Splicing Through RBM20

    This article has 13 authors:
    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
    This article has been curated by 1 group:
    • 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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  5. TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons

    This article has 5 authors:
    1. Wendy W.S. Yue
    2. Lin Yuan
    3. Joao M. Bráz
    4. Allan I. Basbaum
    5. David Julius
    This article has been curated by 1 group:
    • 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.)

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    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  6. Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

    This article has 17 authors:
    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. Leteisha 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
    This article has been curated by 1 group:
    • 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.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  7. Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T 3 ) supplementation

    This article has 10 authors:
    1. Leonardo VinĂ­cius 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
    This article has been curated by 1 group:
    • 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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  8. Semaphorin3F reduces vascular endothelial and smooth muscle cell PI3K activation and decreases neointimal plaque formation

    This article has 20 authors:
    1. Chutima Rattanasopa
    2. David Castano-Mayan
    3. Chengxun Su
    4. Aaron J. Farrugia
    5. Maria Corlianò
    6. Pakhwan Nilcham
    7. Crystal Pang
    8. Monalisa Hota
    9. Koh Ser Mei
    10. Wendy Lee
    11. Dasan Mary Cibi
    12. Atsu Aiba
    13. Manvendra K. Singh
    14. Siew Cheng Wong
    15. Olaf Rotzschke
    16. Alexander Bershadsky
    17. Han Wei Hou
    18. Elisa A. Liehn
    19. Sujoy Ghosh
    20. Roshni R. Singaraja
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors provide novel evidence that semaphorin signaling (SEMA3F) is engaged in the vascular endothelium and smooth muscle to confer atheroprotection. They show that SEMA3F reduces the activity of key enzyme Phosphoinositide 3-kinase to decrease smooth muscle cell proliferation, migration, and phenotype switching, which contributes to atheroprotection. The study has significant translational potential and yields a new therapeutic target.

      (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.)

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  9. Connexin Hemichannels with Prostaglandin Release in Anabolic Function of Bone to Mechanical Loading

    This article has 7 authors:
    1. Dezhi Zhao
    2. Manuel A. Riquelme
    3. Teja Guda
    4. Chao Tu
    5. Huiyun Xu
    6. Sumin Gu
    7. Jean X. Jiang
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors have used two transgenic mouse models expressing dominant negative Cx43 mutants to evaluate the role of Cx43 hemichannels in mechanical loading response in bone. While understanding the molecular mechanisms by which osteocytes respond to mechanical strain is of interest in the skeletal biology arena, the conclusions of this study are not fully supported by experimental data and are of only incremental in nature.

      (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.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  10. Septin-7 is indispensable for proper skeletal muscle architecture and function

    This article has 13 authors:
    1. Mónika Gönczi
    2. Zsolt Ráduly
    3. László Szabó
    4. János Fodor
    5. Andrea Telek
    6. NĂłra Dobrosi
    7. Norbert Balogh
    8. PĂ©ter Szentesi
    9. Gréta Kis
    10. MiklĂłs Antal
    11. György Trencsényi
    12. Beatrix Dienes
    13. László Csernoch
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The study of previously unexplored roles of a cytoskeleton protein termed Septin-7 in muscle could be a significant contribution to understand muscle development and regeneration. The majority of the data support the importance of Septin-7 protein in muscle physiology. With some additional experiments and data analysis to strengthen the mechanistic characterization of Septin-7 in muscle physiology, this manuscript will be of broad interest to readers in the skeletal muscle research 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 #2 agreed to share their name with the authors.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  11. Residual force enhancement within the human quadriceps is greatest during submaximal stretch-hold contractions at a very long muscle length

    This article has 4 authors:
    1. Patrick Bakenecker
    2. Tobias Weingarten
    3. Daniel Hahn
    4. Brent Raiteri
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors have systematically examined relationships between muscle length and force potentiation in young adults using very carefully conducted and controlled measurements by dynamometry and estimated using patellar tendon shear wave speed. The paper should be of interest to those who study human performance.

      (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.)

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  12. Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

    This article has 13 authors:
    1. Xiaoyi Mo
    2. Peiyuan Pang
    3. Yulin Wang
    4. Dexiang Jiang
    5. Mengyu Zhang
    6. Yang Li
    7. Peiyu Wang
    8. Qizhi Geng
    9. Chang Xie
    10. Hai-Ning Du
    11. Bo Zhong
    12. Dongdong Li
    13. Jing Yao
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The TRPV2 channel plays essential roles in many cell types in the body, including macrophages and cardiomyocytes, but its physiological mechanisms of activation and regulation remain largely unknown. Mo and collaborators describe a novel regulatory mechanism of TRPV2 channels in which phosphorylation at three different tyrosine residues by JAK1 sensitizes channels to activation by 2-APB and heat, whereas de-phosphorylation by PTPN1 reverses sensitization. Changes in the dynamics of TRPV2 channel phosphorylation could have important physiological consequences in many cell types expressing these channels. The data are of significant importance for the scientific community interested in function und relevance of transient receptor potential ion channels.

      (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.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  13. Discovery and functional assessment of a novel adipocyte population driven by intracellular Wnt/β-catenin signaling in mammals

    This article has 9 authors:
    1. Zhi Liu
    2. Tian Chen
    3. Sicheng Zhang
    4. Tianfang Yang
    5. Yun Gong
    6. Hong-Wen Deng
    7. Ding Bai
    8. Weidong Tian
    9. YiPing Chen
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      It is becoming increasingly clear that adipocytes are not homogenous, but rather comprise several distinct subtypes with specific physiological functions. This work presents evidence for the surprising finding of a subpopulation of adipocytes displaying non-canonical Wnt signaling. The possible role of these adipocytes in thermogenesis is more ambiguous, and their physiological function remains unclear.

      (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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  14. Unbiased Proteomics, Histochemistry, and Mitochondrial DNA Copy Number Reveal Better Mitochondrial Health in Muscle of High Functioning Octogenarians

    This article has 10 authors:
    1. Ceereena Ubaida-Mohien
    2. Sally Spendiff
    3. Alexey Lyashkov
    4. Ruin Moaddel
    5. Norah J. MacMillan
    6. Marie-Eve Filion
    7. Jose A. Morais
    8. Tanja Taivassalo
    9. Luigi Ferrucci
    10. Russell T. Hepple
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This study analyzed muscle protein differences between octogenarian master athletes and non-athletes. The data showed that high physical function in octogenarians was associated with the increased mitochondrial proteome, reduced number of muscle fibers impaired by oxphos, and higher mtDNA copy number. The authors propose that this is one of the mechanisms contributing to better performance in master athletes compared with non-athletes, suggesting that mitochondrial health in skeletal muscle is a key feature in inducing improved physical function in the elderly. This article has the potential to generate a significant impact within the field and will be of interest to a broad 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 name with the authors.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  15. Post-translational modification patterns on β-myosin heavy chain are altered in ischemic and non-ischemic human hearts

    This article has 15 authors:
    1. Maicon Landim-Vieira
    2. Matthew C. Childers
    3. Amanda L. Wacker
    4. Michelle Rodriguez Garcia
    5. Huan He
    6. Rakesh Singh
    7. Elizabeth A. Brundage
    8. Jamie R. Johnston
    9. Bryan A. Whitson
    10. P. Bryant Chase
    11. Paul M.L. Janssen
    12. Michael Regnier
    13. Brandon J. Biesiadecki
    14. J. Renato Pinto
    15. Michelle S. Parvatiyar
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This study reports new post-translational modifications (PTMs) to β-myosin heavy chain, using tissue samples from normal and failing human hearts. Atomistic simulations of myosin molecular dynamics suggest that these PTMs lead to meaningful alterations in structure, solvent exposure, and dynamics of certain regions of the protein. These data and simulations provide a foundation for further work to determine the precise functional significance of β-myosin heavy chain PTMs. The work will be of interest to cell biologists and cardiologists.

      (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.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  16. Genetic variation of human myokine signaling is dominated by biologic sex and sex hormones

    This article has 7 authors:
    1. Leandro M. Velez
    2. Cassandra Van
    3. Timothy M. Moore
    4. Zhenqi Zhou
    5. Casey Johnson
    6. Andrea L. Hevener
    7. Marcus M. Seldin
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This elegantly performed systems-genetics paper on the predicted human skeletal muscle secretome highlights the importance of sex and sex hormones in regulating myokine expression and predicted cross-tissue effects. Male and female mice lacking estrogen receptor α (Esr1) were used to understand how estrogen signalling affects myokine genes expression. The methods used and data presented in this manuscript can serve as an important resource for other researchers 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 #3 agreed to share their name with the authors.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  17. Inhibition of the sodium-dependent HCO 3 - transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype

    This article has 12 authors:
    1. Vinciane Saint-Criq
    2. Anita Guequén
    3. Amber Philp
    4. Sandra Villanueva
    5. Tábata Apablaza
    6. Ignacio Fernández-Moncada
    7. AgustĂ­n Mansilla
    8. Livia Delpiano
    9. Iván Ruminot
    10. Cristian Carrasco
    11. Michael A. Gray
    12. Carlos A. Flores
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This paper is of interest to scientists and clinicians within the field of muco-obstructive diseases in the airways, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). It identifies the sodium-bicarbonate cotransporter SLC4A4 as a key component of the mechanism by which normal airways prevent the formation of sticky mucus and defend theirselves against bacterial and viral infections.

      (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.)

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  18. Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

    This article has 11 authors:
    1. Priya Balasubramanian
    2. Anne E. Schaar
    3. Grace E. Gustafson
    4. Alex B. Smith
    5. Porsha R. Howell
    6. Angela Greenman
    7. Scott Baum
    8. Ricki J. Colman
    9. Dudley W. Lamming
    10. Gary Diffee
    11. Rozalyn M. Anderson
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      In this manuscript, the authors provide promising results for the treatment of age-related sarcopenia with AdipoRon, a drug that targets the receptors for adiponectin. This is a well done study using an agonist (AdipoRon) involved in lipid and mitochondrial metabolism regulation to mitigate age related muscle loss in mice.

      (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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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  19. Ca 2+ -inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM

    This article has 2 authors:
    1. Ashok R. Nayak
    2. Montserrat SamsĂł
    This article has been curated by 1 group:
    • 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.)

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  20. A plasma membrane-localized polycystin-1/polycystin-2 complex in endothelial cells elicits vasodilation

    This article has 8 authors:
    1. Charles E. Mackay
    2. Miranda Floen
    3. M. Dennis Leo
    4. Raquibul Hasan
    5. Carlos Fernández-Peña
    6. Purnima Singh
    7. Kafait U. Malik
    8. Jonathan H. Jaggar
    This article has been curated by 1 group:
    • 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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity