Physiology

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

1. Duilio M. Potenza
2. Xin Cheng
3. Guillaume Ajalbert
4. Andrea Brenna
5. Marie-Noelle Giraud
6. Aurelien Frobert
7. Stephane Cook
8. Kirsten D. Mertz
9. Zhihong Yang
10. Xiu-Fen Ming

• Curated by eLife

  eLife Assessment

  This study provides fundamental information on how Arg-II participates in cardiac aging. The phenotypic data provide convincing evidence of non-cell-autonomous contributions to aging-related pathologies. Overall, the study highlights the importance of intercellular signaling in maintaining cardiac health during aging.

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 and the data and evidence provided are convincing. 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

A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins

1. Daniel J Kelpsch
2. Liyun Zhang
3. James H Thierer
4. Kobe Koren
5. Urmi Kumar
6. Yuki Lin
7. Monica R Hensley
8. Mira Sohn
9. Jun O Liu
10. Thomas Lectka
11. Jeff S Mumm
12. Steven A Farber

• Curated by eLife

  eLife Assessment

  In this important study, the authors have performed a zebrafish drug screen to identify suppressors of atherogenic lipoproteins. They utilize a well-established LipoGlo assay to find molecules that modulate these lipoproteins, identifying 49 potential hits. They perform some validation experiments, including studies linking enoxolone to its likely inhibitory effect on a specific transcription factor, HNF4alpha. Overall, the results are convincing and robust, and will open up new areas of exploration for those investigators interested in in vivo lipid biology.

Reviewed by eLife

The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming

1. Zachary W Grimmett
2. Rongli Zhang
3. Hua-Lin Zhou
4. Qiuying Chen
5. Dawson Miller
6. Zhaoxia Qian
7. Justin Lin
8. Riti Kalra
9. Steven S Gross
10. Walter J Koch
11. Richard T Premont
12. Jonathan S Stamler

• Curated by eLife

  eLife Assessment

  This study presents compelling evidence that the denitrosylase SCoR2 regulates cardioprotective metabolic reprogramming in the heart following ischemia/reperfusion injury. The findings are supported by a novel multi-omics approach and the integration of mouse and human data, which provides valuable insights into S-nitrosylation and cardiac metabolism. However, some conclusions remain limited by unresolved methodological issues that warrant clarification.

Reviewed by eLife

Effects of Arginine Vasopressin on Islet Cells in Pancreatic Tissue Slices: Glucose-Dependent Modulation of IP3 Receptor-Specific Responses

1. Jasmina Kerčmar
2. Nastja Murko
3. Lidija Križančić Bombek
4. Eva Paradiž Leitgeb
5. Johannes Pfabe
6. Sandra Postić
7. Ya-Chi Huang
8. Andraž Stožer
9. Dean Korošak
10. Xaver Kozisek
11. Monika Perisic
12. Markus Muttenthaler
13. Christian W Gruber
14. Marjan Slak Rupnik

• Curated by eLife

  eLife Assessment

  This study presents a useful finding on the effects of arginine vasopressin (AVP) on islet cells in pancreatic tissue slices, using technically sophisticated spatio-temporal calcium recordings to confirm that AVP influences α and β cells differently depending on glucose concentrations. While the study’s methods – particularly the calcium imaging techniques and peptide ligand design targeting V1b receptors – are strong, the reviewers were concerned about several aspects of the experimental design. The results on β-cell responses are incomplete and insufficient to support the manuscript’s claims, especially due to the high variability of islet responses and lack of mechanistic and functional (hormone release) data. There are also concerns about the possibility of off-target effects and suboptimal receptor specificity: the study would be significantly strengthened by inclusion of signaling pathway interrogation, hormone output assays, genetic validation (e.g., β cell-specific deletion of V1br), and receptor localization. The work will still be of interest to researchers studying islet physiology in the context of health and diabetes.

Reviewed by eLife

Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan

1. Sarah M. Zala
2. Renata Santos
3. Eva Strasser
4. Alice Schadde
5. Sarah Kugler
6. Verena Strauss
7. Anna Kübber-Heiss
8. Diana Zala

Reviewed by PREreview

Iron-deplete diet enhances Caenorhabditis elegans lifespan via oxidative stress response pathways

1. Priyanka Das
2. Ravi
3. Jogender Singh

Reviewed by Review Commons

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