Physiology

Endurance Exercise Ameliorates Aging-Related Bradyarrhythmia in Drosophila Resulting from miR-283 Knockdown in LNvs

1. Qiufang Li
2. Xu Ping
3. Zhengwen Yu
4. Qin Yi
5. Chao Tang
6. Xiaoya Wang
7. Lan Zheng

• Curated by eLife

  eLife Assessment

  This study offers valuable insights into the role of miR-283 in ventral-lateral neurons (LNvs) and its impact on senescence, cardiac function, and aging in the Drosophila melanogaster model. However, the evidence supporting some of the conclusions remains incomplete, and further mechanistic studies are needed to clarify how miR-283 affects normal aging and influences exercise adaptations. Nonetheless, the work can be of interest to cell biologists studying miRNA biology, aging, and age-related diseases.

Reviewed by eLife

Zinc is a Key Regulator of the Sperm-Specific K+ Channel (Slo3) Function

1. Rizki Tsari Andriani
2. Tanadet Pipatpolkai
3. Haruhiko Miyata
4. Masahito Ikawa
5. Yasushi Okamura
6. Takafumi Kawai

• Curated by eLife

  eLife Assessment

  This study presents a useful contribution to understanding zinc regulation of sperm physiology, specifically its inhibitory effects on the sperm-specific potassium channel Slo3. However, the evidence supporting the claims is incomplete, as critical experimental controls are lacking, key mechanistic aspects remain insufficiently explored, and experimental descriptions are often inadequate, making it difficult to fully assess the findings. Strengthening the study with additional electrophysiological recordings in sperm cells, improved imaging controls, and clearer methodological descriptions would enhance its impact and rigor.

Reviewed by eLife

Peripheral opioid receptor antagonism alleviates fentanyl-induced cardiorespiratory depression and is devoid of aversive behavior

1. Brian C Ruyle
2. Sarah Masud
3. Rohith Kesaraju
4. Mubariz Tahirkheli
5. Juhi Modh
6. Caroline G Roth
7. Sofia Angulo-Lopera
8. Tania Lintz
9. Jessica A Higginbotham
10. Nicolas Massaly
11. Jose A Morón

• Curated by eLife

  eLife Assessment

  This manuscript represents a fundamental contribution demonstrating that fentanyl-induced respiratory depression can be reversed with a peripherally-restricted mu opioid receptor antagonist. The paper reports compelling and rigorous physiological, pharmacokinetic, and behavioral evidence supporting this major claim, and furthers mechanistic understanding of how peripheral opioid receptors contribute to respiratory depression. These findings reshape our understanding of opioid-related effects on respiration and have significant therapeutic implications given that medications currently used to reverse opioid overdose (such as naloxone) produce severe aversive and withdrawal effects via actions within the central nervous system.

Reviewed by eLife

Loss of CTRP10 results in female obesity with preserved metabolic health

1. Fangluo Chen
2. Dylan C Sarver
3. Muzna Saqib
4. Leandro M Velez
5. Susan Aja
6. Marcus M Seldin
7. G William Wong

• Curated by eLife

  eLife Assessment

  This manuscript presents a detailed characterization of male and female wildtype and Ctrp10 knockout mice, and reveals that knockout mice develop female-specific obesity that is largely uncoupled from metabolic dysfunction. The data are convincing, and the work will be an important contribution to understanding how obesity is coupled to metabolic dysfunction, and how this can occur in a sex-specific manner.

Reviewed by eLife

Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche

1. Claire Masson
2. Cyril Scandola
3. Jean-Yves Rinckel
4. Fabienne Proamer
5. Emily Janus-Bell
6. Fareeha Batool
7. Naël Osmani
8. Jacky G Goetz
9. Léa Mallo
10. Catherine Léon
11. Alicia Bornert
12. Renaud Poincloux
13. Olivier Destaing
14. Alma Mansson
15. Hong Qian
16. Maxime Lehmann
17. Anita Eckly

• Curated by eLife

  eLife Assessment

  The authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong and solid conclusion is based on the use of state-of-the art techniques such as the use of primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis.

Reviewed by preLights, eLife

Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction

1. Yoshiko M Ikushima
2. Kuan-Chan Chen
3. Richard J. Sulston
4. Domenico Mattiucci
5. Eleanor J. Brain
6. Stefanie A Fung Xin Zi
7. Karla J. Suchacki
8. Benjamin J. Thomas
9. Andrea Lovdel
10. Matthew Bennett
11. Hiroshi Kobayashi
12. Phillip D. Whitfield
13. Keiyo Takubo
14. Andrew H. Baker
15. Nicholas M. Morton
16. Robert K. Semple
17. William P. Cawthorn

Reviewed by PREreview

The Kv2.2 channel mediates the inhibition of prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β-cells

1. Chengfang Pan
2. Ying Liu
3. Liangya Wang
4. Wen-Yong Fan
5. Yunzhi Ni
6. Xuefeng Zhang
7. Di Wu
8. Chenyang Li
9. Jin Li
10. Zhaoyang Li
11. Rui Liu
12. Changlong Hu

• Curated by eLife

  eLife Assessment

  The study presents valuable findings on the molecular mechanisms of glucose-stimulated insulin secretion from pancreatic islets, focusing on the main regulatory elements of the signaling pathway in physiological conditions. While the evidence supporting the conclusions is solid, the study can be strengthened by the use of a beta cell line or knockout mice. The work will be of interest to cell biologists and biochemists working on diabetes.

Reviewed by eLife

Blood pressure variability compromises vascular function in middle-aged mice

1. Perenkita J Mendiola
2. Philip O’Herron
3. Kun Xie
4. Michael W Brands
5. Weston Bush
6. Rachel E Patterson
7. Valeria Di Stefano
8. Jessica A Filosa

• Curated by eLife

  eLife Assessment

  This is an important study providing convincing evidence that increased blood pressure variability impairs myogenic tone and diminishes baroreceptor reflex. The study also provides evidence that blood pressure variability blunts functional hyperemia and contributes to cognitive decline. The authors use appropriate and validated methodology in line with the current state-of-the-art.

Reviewed by eLife

Neuronal Detection Triggers Systemic Digestive Shutdown in Response to Adverse Food Sources

1. Yating Liu
2. Guojing Tian
3. Ziyi Wang
4. Junkang Zheng
5. Huimin Liu
6. Sucheng Zhu
7. Zhao Shan
8. Bin Qi

• Curated by eLife

  eLife Assessment

  This important study investigates how signals from the nervous system can influence the response to different food sources. To demonstrate the role of specific neuronal and intestinal regulators in sensing food quality and modulating digestion, the authors present evidence through a combination of genetic screening, RNA-seq analysis, and functional studies. While the findings shed light on an adaptive strategy to integrate food perception with physiological responses, the evidence presented varies between convincing and incomplete, and additional experiments are needed to more fully support their central hypothesis.

Reviewed by eLife

TRPV4 overactivation enhances cellular contractility and drives ocular hypertension in TGFβ2 overexpressing eyes

1. Christopher N Rudzitis
2. Monika Lakk
3. Ayushi Singh
4. Sarah N Redmon
5. Denisa Kirdajova
6. Yun-Ting Tseng
7. Michael L De Ieso
8. W Daniel Stamer
9. Samuel Herberg
10. David Križaj

• Curated by eLife

  eLife Assessment

  This fundamental work extends our understanding of the role of TGFβ2 as a modulator of mechanosensing in the eye and identifies the TRPV4 ion channel as a common regulator of Trabecular Meshwork (TM) contractility and pathological OHT. The data and evidence are convincing, with some minor limitations. This work will clearly be of interest to researchers investigating the role of mechanosensors in the TM and may underpin future research into treatments that aim to lower intra ocular pressure. This work will additionally be of interest to the growing field of researchers investigating the regulation of force sensing via ion channels and their roles in health and disease, in particular the ion channel TRPV4.

Reviewed by eLife