Physiology

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 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

Slusarczyk et al demonstrate that red pulp macrophages (RPM), specialized splenic cells that clear senescent red blood cells through erythrophagocytosis, show diminished function in aging mice. This impairment leads to retention of hemolytic red blood cells and formation of extracellular aggregates which further exacerbate RPM demise. Iron restriction alleviates most of these symptoms in aging RPMs. They propose RPM collapse as an early indicator of aging that could be reversed through iron limitation.

eLife assessment

Masschelin et al. investigate the role of Vitamin B2 (riboflavin), an essential cofactor for FAD and FMN coenzymes involved in the electron transport chain and TCA cycle, in fasting glucose metabolism. This study phenotypes B2-deficient mice liver and provides valuable data on genes and metabolites that are changed with B2 depletion +/- Fenofibrate administration. The work employs solid methodology and will be of interest to liver physiologists interested in fasting in the context of PPAR.

eLife assessment

McKay, et al. describe development of a new wireless, network-enabled automated feeder system with which diet amount and schedule can be controlled across individually housed killifish. The system is constructed using open-source components and software and is amenable to manufacture by individual research groups and is highly scalable. The authors then use this system to explore dietary restriction effects on killifish lifespan and to develop an associative learning assay, two important goals in the KF /longevity field. The authors demonstrate that precise control of food allows automated investigation of lifespan extension under calorie restriction conditions. Secondly, they show an exciting modification of the system that involves only addition of a simple LED light. This modification allows use of the system in an associative learning / conditioning paradigm. Finally, using this paradigm, they demonstrate an age-dependent decline in learning.