Physiology

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

Progressive postnatal hearing development limits early parent-offspring vocal communication in the zebra finch

1. Tommi Anttonen
2. Jakob Christensen-Dalsgaard
3. Coen PH Elemans

• Curated by eLife

  eLife Assessment

  Zebra finches are a prominent model system for vocal learning and auditory system function, yet little is known about the functional development of the auditory system. Here, the authors convincingly show that newly hatched zebra finches lack detectable auditory brainstem responses and that auditory neural signals emerge only days after hatching, challenging influential claims of prenatal acoustic communication in altricial birds. This important work clarifies the developmental timeline for auditory communication and highlights the value of neuroscientific methods for validating and complementing behavioral ecological studies of animal perception.

Reviewed by eLife

NAD+ boosting by oral nicotinamide mononucleotide administration regulates key metabolic and immune pathways through SIRT1 dependent and independent mechanisms to mitigate diet-induced obesity and dyslipidemia in mice

1. Yasser Majeed
2. Najeeb M Halabi
3. Rudolf Engelke
4. Hina Sarwath
5. Muna N Al-Noubi
6. Sunkyu Choi
7. Aisha Al-Malki
8. Maha V Agha
9. Muneera Vakayil
10. Lotfi Chouchane
11. Frank Schmidt
12. Nayef A Mazloum

• Curated by eLife

  eLife Assessment

  The mechanistic basis for the potential health benefits of NAD⁺ precursors remains incompletely understood. This manuscript provides a useful assessment of the role of SIRT1 in mediating the effects of NMN in mice fed a high-fat diet. The study addresses a key question, though some of the conclusions appear only partially supported by the presented data.

Reviewed by eLife

The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch

1. Robbert van der Pijl
2. Jochen Gohlke
3. Joshua Strom
4. Eva Peters
5. Shengyi Shen
6. Stefan Conijn
7. Zaynab Hourani
8. Stephan Lange
9. Ju Chen
10. Paul Langlais
11. Siegfried Labeit
12. Henk Granzier
13. Coen Ottenheijm

• Curated by eLife

  eLife Assessment

  The study presents important insights into the regulation of muscle hypertrophy, regulated by Muscle Ankyrin Repeat Proteins (MARPs) and mTOR. The methods are overall solid and complementary, with only minor limitations. Overall, the findings will be of interest for both muscle-biology specialists and the broader mechanobiology community.

Reviewed by eLife

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis in Drosophila

1. Jayati Gera
2. Marishia Agard
3. Hannah Nave
4. Austin B Baldridge
5. Farwa Sajadi
6. Leena Thorat
7. Theresa H McKim
8. Shu Kondo
9. Dick R Nässel
10. Mitchell H Omar
11. Jean-Paul Paluzzi
12. Meet Zandawala

• Curated by eLife

  eLife Assessment

  The authors used comprehensive approaches to identify Gyc76C as an ITPa receptor in Drosophila. They revealed that ITPa acts via Gyc76C in the renal tubules and fat body to modulate osmotic and metabolic homeostasis. The designed experiments, data, and analyses convincingly support the main claims. The findings are important to help us better understand how ITP signals contributes to systemic homeostasis regulation.

Reviewed by eLife

Thermogenic Adipose ADH5 Counteracts Age-related Metabolic Decline

1. Sara C Sebag
2. Tate Neff
3. Qingwen Qian
4. Arvand Asghari
5. Zhuozhi Wang
6. Zeyuan Zhang
7. Mark Li
8. Meihua Hao
9. Vitor A Lira
10. Hongli Sun
11. Matthew J Potthoff
12. Ling Yang

• Curated by eLife

  eLife Assessment

  This valuable study identifies a brown adipose tissue-specific heat shock factor 1-alcohol dehydrogenase 5 (ADH5) molecular cascade as a regulator of systemic aging, showing that ADH5 deficiency contributes to BAT dysfunction and health decline in aged mice. While there is evidence to support this mechanism, the conclusions remain incomplete, particularly regarding statistical rigor and clarity in data presentation.

Reviewed by eLife

Orco regulates the circadian activity of pheromone-sensitive olfactory receptor neurons in hawkmoths

1. Aditi Vijayan
2. Mauro Forlino
3. Yajun Chang
4. Pablo Rojas
5. Katrin Schröder
6. Anna C Schneider
7. Martin E Garcia
8. Monika Stengl

• Curated by eLife

  eLife Assessment

  In this manuscript, the authors used in vivo long-term tip recordings of the long trichoid sensilla of male hawkmoths to analyze spontaneous spiking activity indicative of the ORNs' endogenous membrane potential oscillations. The authors combine extracellular electrophysiology of the hawkmoth antennae with computational modeling to predict that Orco receptor neuron (ORN) activity is required for circadian, not ultradian, firing patterns. The work provides valuable support for the hypothesis that a posttranslational feedback loop regulates daily and ultradian rhythms in neuronal excitability. Nevertheless, the evidence reported provides only incomplete support for their conclusions, especially with regard to the biological implications of their assumption-heavy models.

Reviewed by eLife

E4BP4 Safeguards Brown Fat Mitochondria from Obesity-Induced Fragmentation via Ceramide Repression

1. Fernando Valdivieso-Rivera
2. Vanessa O. Furino
3. Carlos E. Leher
4. Ariane M. Zanesco
5. Monara Kaélle Cruz
6. Flavia C. Gan
7. Adriana Leandra Santoro
8. Lara Regina-Ferreira
9. Giovanna Leite Santos
10. Tiago Gonçalves
11. Luiz Osório Leiria
12. Pedro M. Moraes-Vieira
13. Roger Frigério Castilho
14. Shingo Kajimura
15. Marcelo A. Mori
16. Licio A. Velloso
17. Carlos H. Sponton

Reviewed by Review Commons

Modeling metabolic disease susceptibility and resilience in genetically diverse mice

1. Candice N Baker
2. Jeffrey M Harder
3. Daniel A Skelly
4. Isabella Gerdes Gyuricza
5. Margaret Gaca
6. Matthew Vincent
7. Allison Ingalls
8. Mark P Keller
9. Alan D Attie
10. Madeleine Braun
11. Michael Stitzel
12. Edison T Liu
13. Nadia Rosenthal
14. Gary A Churchill

• Curated by eLife

  eLife Assessment

  The authors used three genetically diverse mouse models to investigate the impact of genome diversity on metabolic disease outcomes, such as obesity and glucose tolerance. This study is important because it integrates comprehensive metabolic analyses and multi-tissue phenotyping across sexes to reveal pathways relevant to obesity and its complications; the data are convincing and uncover several pathways that advance understanding of disease etiology while suggesting potential therapeutic avenues to prevent obesity-related health risks. There are limitations, such as a limited number of mouse strains used in the work, the 9-week feeding regime may be too short to capture full metabolic remodeling, and the mechanisms by which the immune-adipose axis impacts the broader phenotype are not fully described. Overall, the study is compelling, but the manuscript could be improved by justifying the strain selection, addressing the concern about the feeding duration, and providing stronger mechanistic support or discussion.

Reviewed by eLife