There is emerging interest in stem cell energy metabolism and its effect on differentiation. Bioenergetic changes in differentiating bone marrow mesenchymal stem cells (MSCs) are poorly understood and were the focus of our study. Using bioenergetic profiling and transcriptomics, we have established that MSCs activate the mitochondrial process of oxidative phosphorylation (OxPhos) during osteogenic differentiation, but they maintain levels of glycolysis similar to undifferentiated cells. Consistent with their glycolytic phenotype, undifferentiated MSCs have high levels of hypoxia-inducible factor 1 (HIF-1). Osteogenically induced MSCs downregulate HIF-1 and this downregulation is required for activation of OxPhos. In summary, our work provides important insights on MSC bioenergetics and proposes a HIF-based mechanism of regulation of mitochondrial OxPhos in MSCs.

Background  Previous research has identified various dimensions of social support that are positively associated with parental well‐being. However, most research does not include multiple measures of social support and uses heterogeneous samples in terms of child characteristics such as age and severity of intellectual disability. Methods  Thirty‐three parents of adolescent children with moderate–profound intellectual disabilities completed measures of parental well‐being (stress, anxiety and depression, and caregiving satisfaction), social support (informal and formal sources, and practical and emotional support), and child characteristics (adaptive and problem behaviours). Results  Correlation analyses showed that parental well‐being was associated with the child's adaptive and problem behaviours and with the child's autism diagnosis. Parents’ ratings of the helpfulness of informal sources of support (spouse, extended family, friends, etc.) was most reliably associated with parental well‐being, and remained so after controlling for child characteristics. Parents’ access of service and professional support was not associated with parental well‐being, but there was some evidence that it was related to their child's needs. Conclusions  The research emphasizes the significance of including multiple measures of social support in research with families of children with an intellectual disability. Furthermore, the possibility that parents, during their child's adolescence, may be especially vulnerable to the disruption of their informal support networks is an important practical consideration.

Fungal physiology refers to the nutrition, metabolism, growth, reproduction and death of fungal cells. It also generally relates to interaction of fungi with their biotic and abiotic environment, including cellular responses to stress. The physiology of fungal cells impacts significantly on the environment, industrial processes and human health. In relation to ecological aspects, the biogeochemical cycling of carbon in nature would not be possible without the participation of fungi acting as primary decomposers of organic material. Furthermore, in agricultural operations, fungi play important roles as mutualistic symbionts, pathogens and saprophytes, where they mobilize nutrients and affect the physico-chemical environment. Fungal metabolism is also responsible for the detoxification of organic pollutants and for bioremediating heavy metals in the environment. The production of many economically important industrial commodities relies on the exploitation of yeast and fungal metabolism, and these include such diverse products as whole foods, food additives, fermented beverages, antibiotics, probiotics, pigments, pharmaceuticals, biofuels, enzymes, vitamins, organic and fatty acids and sterols. In terms of human health, some yeasts and fungi represent major opportunistic life-threatening pathogens, whilst others are life-savers, as they provide antimicrobial and chemotherapeutic agents. In modern biotechnology, several yeast species are being exploited as ideal hosts for the expression of human therapeutic proteins following recombinant DNA technology. In addition to the direct industrial exploitation of yeasts and fungi, it is important Fungi: Biology and Applications, Second Edition. Edited by Kevin Kavanagh.

Bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) can differentiate into osteoblasts (OBs), adipocytes, or chondrocytes. As BMSCs undergo OB differentiation, they up-regulate mitochondrial oxidative phosphorylation (OxPhos). Here, we investigated the mechanism(s) connecting mitochondrial OxPhos to OB differentiation. First, we found that treating BMSC-like C3H10T1/2 cells with an OxPhos inhibitor reduces their osteogenic potential. Interestingly, ATP levels were not reduced, as glycolysis compensated for the decreased OxPhos. Thus, mitochondria support OB differentiation not only by supplying ATP, but also by other mechanisms. To uncover these mechanisms, we stimulated OxPhos in C3H10T1/2 cells by replacing media glucose with galactose and observed that this substitution increases both OxPhos and osteogenesis even in the absence of osteoinducers. β-Catenin, an important signaling pathway in osteogenesis, was found to be responsive to OxPhos stimulation. β-Catenin activity is maintained by acetylation, and mitochondria generate the acetyl donor acetyl-CoA, which upon entering the Krebs cycle is converted to citrate capable of exiting mitochondria. Cytosolic citrate is converted back to acetyl-CoA by ATP citrate lyase (ACLY). We found that inhibiting ACLY with SB204990 (SB) reverses the galactose-induced β-catenin activity and OB differentiation. This suggested that acetylation is involved in β-catenin activation after forced OxPhos stimulation, and using immunoprecipitation, we indeed detected SB-sensitive β-catenin acetylation. Both β-catenin acetylation and activity increased during osteoinduction coincident with OxPhos activation. These findings suggest that active mitochondria support OB differentiation by promoting β-catenin acetylation and thus activity.

Fungi are one of the most important and widespread components of the biosphere, and are essential for the growth of over 90% of all vascular plants. Although they are a separate kingdom of life, we know relatively little about the origins of their ubiquitous existence. This reflects a wider ignorance arising from their status as indeterminate organisms epitomized by extreme phenotypic plasticity that is essential for survival in complex environments. Here we show that the fungal phenotype may have its origins in the defining characteristic of indeterminate organisms, namely their ability to recycle locally immobilized internal resources into a mobilized form capable of being directed to new internal sinks. We show that phenotype can be modelled as an emergent phenomenon resulting from the interplay between simple local processes governing uptake and remobilization of internal resources, and macroscopic processes associated with their transport. Observed complex growth forms are reproduced and the sensitive dependence of phenotype on environmental context may be understood in terms of nonlinearities associated with regulation of the recycling apparatus.