Physiology

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.

eLife assessment

This important study describes changes in excitability in motor neurons of the peripheral autonomous nervous system during aging. The manuscript provides convincing evidence indicating that sympathetic neurons from aged mice show higher excitability compared to neurons from young mice which was linked to decreased activity of KCNQ2/3 potassium channels. This research has implications for understanding the age-related changes that occur in the peripheral nervous system.

eLife assessment

This manuscript presents important observations on the early changes that occur in calcium signaling, TMEM16a channel activation, and mitochondrial dysfunction in salivary gland cells in a murine model of autoimmune Sjögren's disease. The study reports that in response to DMXAA treatment which induces a murine model of Sjögren's disease, salivary gland cells show significant changes in saliva release, calcium signaling, TMEM16a activation, mitochondrial function, and sub-cellular morphology of the endoplasmic reticulum. The work is compelling and will be of strong interest to physiologists working on secretion, calcium signaling, and mitochondria.

eLife assessment

The study presents valuable findings on compensatory mechanisms in response to glycosuria. The evidence supporting the claims is solid, although a causal relationship is somewhat uncertain and the addition of a more clinically relevant model would have strengthened the findings. The work will be of interest to diabetes investigators.