Physiology

eLife assessment

This paper reports the fundamental discovery of a new function of neutrophil in specifically clearing apoptotic hepatocytes by penetrating the cells rather than engulfing them without causing inflammation as a part of tissue homeostasis. This solid study transforms the way we think about role of neutrophil in pathogenesis of autoimmune liver disease.

eLife assessment

In this study, the authors made important progress in understanding bone metabolic defects of T2D. They have established a valuable model that could mimic some aspects of T2D in mice. Particularly, the study provided important evidence showing bone turnover and metabolism were in defects, and changes in glycolysis would rescue bone defects in T2D. Overall, the authors provide compelling evidence from dynamic histomorphometry, C13 isotype labeling in vivo, scRNA-seq, and metabolic assays to demonstrate that the defective glucose metabolism causes osteopenia associated with T2D.

eLife assessment

This important paper advances our understanding of the role of lipid peroxidation in loss of muscle mass and force-generating capacity during aging and hind-limb suspension. The evidence is in general solid, drawing from experiments in vivo and cell culture using multiple types of manipulations of the formation of lipid peroxides although some weaknesses were identified. The results should be of interest to those who study the molecular basis for sarcopenia and disuse atrophy of skeletal muscle.

eLife assessment

This paper provides a valuable systematic analysis of proteomic profiles associated with a particular murine Ryanodine receptor abnormality. Its analysis technique provides a solid and systematic set of data summarising the differences in different muscle types. The work emerges with insights into pathological mechanism of congenital muscle diseases linked to mutations in a range of other genes related to excitation contraction coupling in workers within the skeletal muscle field.

eLife assessment:

Bone marrow stromal cells (BMSCs) can differentiate into a variety of cell types such as osteoblasts, chondrocytes, and adipocytes. The authors of this important study provide compelling and strong evidence that ablating O-GlcNAc transferase (OGT) in BMSCs impairs bone formation but promotes marrow adiposity. The results show that the balance of osteogenic and adipogenic differentiation of BMSCs is controlled by reciprocal O-GlcNAc regulation of lineage-specifying transcription factors, and highlights the importance of an intracellular glycosylation process of specific proteins in bone formation and bone marrow adipocytes.

eLife assessment

This study describes an interesting approach using PEGylated isoprenaline to selectively activate beta-adrenergic receptors in the surface sarcolemma of ventricular myocytes. While the concept is compelling, and the core of an interesting and impactful study is presented, the results are preliminary and incomplete at this stage, and would benefit from more rigorous validation of the approach. The work will be of interest to cardiac cell biologists and pharmacologists.

eLife assessment

This manuscript reports novel and important findings on the mechanisms of regulation of CRAC channels. Collectively, the work represents an important conceptual advancement, showing that stromal interaction molecule-1 is not necessary for Ca2+-dependent inactivation of the Orai1 channel and that Orai1 likely contains a Ca2+ sensor for autoregulatio. The experiments are carefully conducted, and the data is of high quality and support the major conclusions of the authors.

eLife assessment

This study presents valuable comprehensive data that underpin the enhanced ventricular arrhythmogenesis in elite trained athletes. The study is logistical challenge and the multiscale approaches used is a strength of the study. The data presented are strong and support most of the authors' claims.

eLife assessment

In this work, the authors provide convincing evidence about the existence of two distinct osteoclast populations with specific expression profiles and properties and show that the probiotic yeast S. boulardii may be useful in managing inflammation-mediated bone loss, including estrogen deprivation-mediated osteoporosis. The reported study aims to bring the concept of heterogeneous osteoclasts into a proof-of-principle therapeutic application, which may mean that the use of probiotics might combat osteoporosis towards a better bone quality than current therapies. The molecular mechanism of how the probiotic yeast S. boulardii treatment acts via the receptors remains obscure since it might act via changes in the gut permeability or by components directly released by the fungus.

eLife assessment

This study presents a valuable finding of the role of under investigated pathway associated with development of placental oxygenation during pregnancy. The evidence supporting the claims of the authors is incomplete, although inclusion of a larger number of patient samples and an animal model have strengthened the study. The work will be of interest to developmental biologists working on placental function.