Dystrophin glycoprotein complex dysfunction:a regulatory link between muscular dystrophy and cancer cachexia

SummaryCachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting

To DGC or not to DGC: oxygen guarding in the termite Zootermopsis nevadensis (Isoptera: Termopsidae)

The ability of some insects to engage in complex orchestrations of tracheal gas exchange has been well demonstrated, but its evolutionary origin remains obscure. According to a recently proposed hypothesis, insects may employ spiracular control of gas exchange to guard tissues against long-term oxidative damage by using the discontinuous gas-exchange cycle (DGC) to limit internal oxygen partial pressure (P_(O_2)). This manuscript describes a different approach to oxygen guarding in the lower termite Zootermopsis nevadensis. These insects do not display a DGC but respond to elevated oxygen concentrations by restricting spiracular area, resulting in a transient decline in CO_2 emission. High internal CO_2 concentrations are then maintained; restoring normoxia results in a transient reciprocal increase in CO_2 emission caused by release of excess endotracheal CO_2. These changes in spiracular area reflect active guarding of low internal O_2 concentrations and demonstrate that regulation of endotracheal hypoxia takes physiological priority over prevention of CO_2 build-up. This adaptation may reflect the need to protect oxygen-sensitive symbionts (or, gut bug guarding). Termites may eschew the DGC because periodic flushing of the tracheal system with air may harm the obligate anaerobes upon which the lower termites depend for survival on their native diet of chewed wood

Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma

Combining direct ground cooling with ground-source heat pumps and district heating: Energy and economic analysis

Direct ground cooling (DGC) is a method used in cold climates to provide cooling to buildings without the use of any mechanical refrigeration. When DGC is utilized for providing cooling, ground-source heat pumps (GSHPs) and district heating (DH) are the two commonly used technologies for providing heating to the buildings. This article investigates the coupling of DGC with GSHPs and DH in terms of purchased energy and lifecycle costs. An office building equipped with active chilled beams for cooling and radiators for heating is used as a reference. Six cases based on different combinations of building envelope characteristics and thus different building heating and cooling loads are considered. The results show that using DGC-DH significantly reduces the amount of purchased electricity. However, the total energy cost is lower when DGC-GSHP is used. In addition, the DGC-GSHP can be more viable when the ground loads are well balanced. Investment costs, including borehole installation and equipment costs, are lower for the DGC-DH in the majority of the investigated cases. The lifecycle cost is lower for the DGC-DH in most of the investigated cases due to lower equipment costs