Physiology

eLife Assessment

This valuable study investigates the oscillatory activity of gonadotropin-releasing hormone (GnRH) neurones in mice using GCaMP fiber photometry. It demonstrates three distinct patterns of oscillatory activity that occur in GnRH neurons comprising low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge. The evidence presented in the study is solid, offering theoretical implications for understanding the behaviour of GnRH neurones in the context of reproductive physiology, and will be of interest to researchers in neuroendocrinology and reproductive biology.

eLife Assessment

This valuable study examines how different exercise training intensities affect intestinal barrier function and gut microbiota composition over a 6-week period in mice. The evidence supporting the main claims about exercise-induced intestinal injury and microbiota changes is solid, featuring comprehensive histological analysis, molecular characterization, and metabolomic profiling, though key mechanistic insights and causal relationships remain to be established. The findings have practical implications for understanding exercise-induced gastrointestinal stress, particularly the observation that daily moderate exercise may be more damaging to intestinal integrity than vigorous exercise with rest days. Additional experimental validation would strengthen these conclusions.

eLife Assessment

This study provides important insights into postnatal lung development and the mechanisms underlying bronchopulmonary dysplasia (BPD), a condition with high morbidity and mortality in newborns. Through the use of neonatal hyperoxia, cell-type-specific inactivation of Tgfbr2, and other injury models, the research focuses on the role of TGF-β signaling in BPD pathogenesis, highlighting impaired myofibroblast proliferation as a key factor. The inactivation of Etc2 in Pdgfra-lineaged cells disrupts myofibroblast cytokinesis, leading to alveolar simplification and reduced cell numbers. The use of transgenic mice and single-cell transcriptomics offers a detailed and high-quality dataset, advancing our understanding of BPD and serving as a invaluable resource for developmental biology and neonatal pulmonary research. The study's comprehensive approach, robust data, and methodological rigor make it a compelling contribution to the field, providing both mechanistic insights and a resource for further research into BPD pathogenesis.

eLife Assessment

This important study investigates the contribution of cytosolic S100A/8 to neutrophil migration to inflamed tissues. The authors provide convincing evidence for how the loss of cytosolic S100A/8 specifically affects the ability of neutrophils to crawl and subsequently adhere under shear stress. This study will be of interest in fields where inflammation is implicated, such as autoimmunity or sepsis.

eLife Assessment

This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.

eLife Assessment

SGLT2 inhibitors (SGLT2i) have assumed important roles in reducing cardiovascular risk, particularly in those with diabetes. It has become appreciated that its protective effects are likely beyond their ability to lower blood sugar levels. This research presents a novel approach to studying the SGLT2i mechanism of action which is yet to be fully elucidated.

eLife Assessment

In this work, the authors propose that astrocytic aquaporin 4 (AQP4) is the main pathway for tonic water efflux, without which astrocytes undergo cell swelling. These findings are important, because they shed light on key molecular mechanisms implicated with the regulation of brain water homeostasis. The authors use a broad set of experimental tools (e.g., acute brain slices, in vivo recording, and diffusion-weighted MRI) but the evidence remains incomplete without ruling out non-specific effects of TGN-020, and without evidence that changes in sulforhodamine B fluorescence can be used as reliable readouts of cell volume dynamics.

eLife Assessment

This study focuses on the regulation of GLP-1 in enteroendocrine L cells and how this may be stimulated by the mechanogated ion channel Piezo1 and the CaMKKbeta-CaMKIV-mTORC1 signaling pathway. The work is innovative and is considered valuable, as the hypothesis that is being tested may have significant mechanistic and translational implications. Data to support the proposed mechanism were considered incomplete, yet data to support the overall physiological characterization were considered solid.

eLife Assessment

This important study reveals insights into how calcineurin influences C. elegans pathogen susceptibility and lifespan through its role in controlling the defecation motor program. The authors provide convincing evidence to support a new mechanism through which calcineurin impacts longevity. This work will be of interest to investigators studying host-pathogen interactions and aging in a number of experimental systems.

eLife assessment

This important study highlights cell types preserving long-lived proteins and lays a foundation for identifying exceptionally long-lived proteins in the ovary. Convincing evidence describes helpful data about protein turnover and identifies long-lived macromolecules in oocytes and somatic cells during mouse ovarian aging. This work will be of interest to researchers working on aging and reproductive health.