Physiology

RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in C. elegans

1. Chung-Chih Liu
2. Nicolas Seban
3. Supriya Srinivasan

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.

Reviewed by eLife

Efficient transduction of pancreas tissue slices with genetically encoded calcium integrators

1. Charles S Lazimi
2. Austin E Stis
3. Julia K Panzer
4. Helmut Hiller
5. Maria L Beery
6. Amelia K Linnemann
7. Cherie L Stabler
8. Clayton E Mathews
9. Edward A Phelps

• Curated by eLife

  eLife Assessment

  This study presents a valuable advance by enabling functional mapping of Ca²⁺ responses in live human pancreatic tissue slices, providing new opportunities to study islet heterogeneity and diabetes-related dysfunction in an intact tissue context. The evidence supporting the main conclusions is solid, based on reproducible methodology and functional validation across multiple human donor samples. Key revisions needed include clearer quantification of transduction efficiency and tissue viability, and improved clarification of how CaMPARI2 signals should be interpreted.

Reviewed by eLife

Non-visual light modulates behavioral memory and gene expression in C. elegans

1. Zhijian Ji
2. Bingying Wang
3. Rashmi Chandra
4. Junqiang Liu
5. Supeng Yang
6. Yong Long
7. Michael Egan
8. Fujia Han
9. Han Wang
10. Noelle L’Etoile
11. Dengke K Ma

• Curated by eLife

  eLife Assessment

  This important study uncovers a previously unrecognized light-responsive pathway in C. elegans that depends on live food bacteria and is mediated by the bZIP factors ZIP-2/CEBP-2 and the cytochrome P450 enzyme, CYP-14A5. The authors show that this bacteria-linked pathway modulates long-term memory and can be harnessed as a low-cost light-inducible expression system, opening new directions for sensory biology and genetic engineering in worms. The exact means by which live bacteria modulate light signal that activates ZIP-2/CEBP-2 in the worm remains to be elucidated. The evidence supporting the pathway's role uses multiple genetic, transcriptional, and behavioural assays, and is convincing.

Reviewed by eLife

SLC4A1 mutations that cause distal renal tubular acidosis alter cytoplasmic pH and cellular autophagy

1. Grace Essuman
2. Midhat Rizvi
3. Ensaf Almomani
4. Shahid AK M Ullah
5. Sarder MA Hasib
6. Forough Chelangarimiyandoab
7. Priyanka Mungara
8. Manfred J Schmitt
9. Marguerite Hureaux
10. Rosa Vargas-Poussou
11. Nicolas Touret
12. Emmanuelle Cordat

• Curated by eLife

  eLife Assessment

  This work reports the characterization of newly identified genetic variants of SLC4A1 in patients with distal renal tubular acidosis. Cell culture studies supplemented with histological analysis of a previously established disease mouse model provide convincing evidence that some of the variants increase intracellular pH, reduce ATP synthesis, and attenuate autophagic degradative flux. The study is valuable in establishing a mechanistic framework for future exploration of the link between intracellular pH and mutations in SLC4A1 in vivo.

Reviewed by eLife

Differential Regulation of Hepatic Macrophage Fate by Chi3l1 in MASLD

1. Jia He
2. Bo Chen
3. Weiju Lu
4. Xiong Wang
5. Ruoxue Yang
6. Chengxiang Deng
7. Xiane Zhu
8. Keqin Wang
9. Lang Wang
10. Cheng Xie
11. Rui Li
12. Xiaokang Lu
13. Ruizhi Yang
14. Cheng Peng
15. Canpeng Li
16. Zhao Shan

• Curated by eLife

  eLife Assessment

  This study investigates the function of Chi3l1 in hepatic macrophages in the context of MASLD, providing useful insights at a time when the distinct roles of Kupffer cells or monocyte-derived macrophages in this disease remain incompletely defined. The data suggests that CHI3L1 in Kupffer cells modulates glucose handling in obesity and mitigates systemic metabolic dysfunction and hepatic steatosis during high-fat, high-fructose feeding. However, the loss-of-function studies employing Kupffer cell restricted versus a pan myeloid Cre lines are not sufficient to support the assertion that CHI3L1 activity is confined to resident Kupffer cells. Additionally, the flow-cytometric analyses reveal a modest depletion of Kupffer cells and no recruitment of TIM4low monocyte-derived macrophages, indicating that the system reflects simple steatosis rather than substantial macrophage turnover or niche remodelling. While the findings are intriguing, further experimentation is required to clarify the cellular specificity and mechanistic basis of the phenotypes observed.

Reviewed by eLife

Sex-biased expression of enteroendocrine cell-derived hormones contributes to higher fat storage in Drosophila females

1. Puja Biswas
2. Elizabeth J Rideout

• Curated by eLife

  eLife Assessment

  This useful study provides a systematic and solid comparison of sex-biased enteroendocrine peptide expression, including AstC and Tk, to show that these peptides contribute to female-biased fat storage. The major research question of this study is based on the authors' previous papers, and therefore, the presented results are incremental. This study serves as a foundation for future investigation of regulatory mechanisms for the sex-biased fat content by AstC and Tk.

Reviewed by eLife

PIEZO channels link mechanical forces to uterine contractions in parturition

1. Yunxiao Zhang
2. Sejal A. Kini
3. Sassan A. Mishkanian
4. Renhao Luo
5. Saba Heydari Seradj
6. Verina H. Leung
7. Yu Wang
8. M. Rocío Servín-Vences
9. William T. Keenan
10. Utku Sonmez
11. Oleg Yarishkin
12. Manuel Sanchez-Alavez
13. Yuejia Liu
14. Xin Jin
15. Darren J. Lipomi
16. Li Ye
17. Michael Petrascheck
18. Antonina I. Frolova
19. Sarah K. England
20. Ardem Patapoutian

Reviewed by PREreview

Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels

1. Michael J Davis
2. Hae Jin Kim
3. Min Li
4. Jorge A Castorena-Gonzalez
5. Soumiya Pal
6. Timothy L Domeier
7. Joshua P Scallan
8. Scott Earley
9. Scott D Zawieja

• Curated by eLife

  eLife Assessment

  Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.

Reviewed by eLife

Cytokine control of systemic hypoxia tolerance in Drosophila

1. Kate Ding
2. Prajakta Bodkhe
3. Byoungchun Lee
4. Danielle Polan
5. Amy Wycislik
6. Tiffany Cheung
7. Sophie Wu
8. Savraj S Grewal

Reviewed by PREreview

Natural xanthones as α-Mangostin induce vasorelaxation via binding to key gating residues in the S6 domain of BK channels

1. Sönke Cordeiro
2. Robert Patejdl
3. Thomas Baukrowitz
4. Marianne Musinszki

• Curated by eLife

  eLife Assessment

  The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels; macroscopic currents and single-channel experiments show that α-mangostin produces an increase in the probability of opening, without affecting the single-channel conductance. The authors put forward that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

Reviewed by eLife