Search

Exercise can alter the skeletal muscle DNA methylome, yet little is known about the role of the DNA methylation machinery in exercise capacity. Here, we show that DNMT3A expression in oxidative red muscle increases greatly following a bout of endurance exercise. Muscle-specific Dnmt3a knockout mice have reduced tolerance to endurance exercise, accompanied by reduction in oxidative capacity and mitochondrial respiration. Moreover, Dnmt3a-deficient muscle overproduces reactive oxygen species (ROS), the major contributors to muscle dysfunction. Mechanistically, we show that DNMT3A suppresses the Aldh1l1 transcription by binding to its promoter region, altering its epigenetic profile. Forced expression of ALDH1L1 elevates NADPH levels, which results in overproduction of ROS by the action of NADPH oxidase complex, ultimately resulting in mitochondrial defects in myotubes. Thus, inhibition of ALDH1L1 pathway can rescue oxidative stress and mitochondrial dysfunction from Dnmt3a deficiency in myotubes. Finally, we show that in vivo knockdown of Aldh1l1 largely rescues exercise intolerance in Dnmt3a-deficient mice. Together, we establish that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.

It has been suggested that beige fat thermogenesis is tightly controlled by epigenetic regulators that sense environmental cues such as temperature. Here, we report that subcutaneous adipose expression of the DNA demethylase TET1 is suppressed by cold and other stimulators of beige adipocyte thermogenesis. TET1 acts as an autonomous repressor of key thermogenic genes, including Ucp1 and Ppargc1a, in beige adipocytes. Adipose-selective Tet1 knockout mice generated by using Fabp4-Cre improves cold tolerance and increases energy expenditure and protects against diet-induced obesity and insulin resistance. Moreover, the suppressive role of TET1 in the thermogenic gene regulation of beige adipocytes is largely DNA demethylase-independent. Rather, TET1 coordinates with HDAC1 to mediate the epigenetic changes to suppress thermogenic gene transcription. Taken together, TET1 is a potent beige-selective epigenetic breaker of the thermogenic gene program. Our findings may lead to a therapeutic strategy to increase energy expenditure in obesity and related metabolic disorders.

High‐temperature (15–37°C) aging can shorten the tenderizing time of beef; however, the use of constant temperature heating can lead to microbial spoilage. This study tested radiofrequency (RF) tenderization (RF‐T) to find the appropriate conditions for the aging‐like effect of beef without microbial spoilage. After subjecting beef to 22 h RF‐T with four different cooling temperatures (15, 5, −10, and −20°C), the proliferated aerobic bacteria on the surface showed a concentration of 6–6.2 log CFU/g at −10 and −20°C, lower than 7–7.5 log CFU/g at 15 and 5°C. When beef was treated with 25 W/kg RF heating power for 48 h RF‐T, the estimated reduction rate of the sliced shear force (SSF) and the increase rate of glutamic acid based on the weight before RF‐T were 22.6% and 1.51‐fold, which were greater than 19.6% and 1.37‐fold with 20 W/kg, and 11.0% and 1.11‐fold with 15 W/kg. The optimal specific RF heating power was calculated as 30 W/kg from the results' extrapolation. When processed for 48 h under optimal conditions (30 W/kg specific RF heating power, −20°C cooling air), the tenderization rate and the increased rates of free amino acids based on the weight before RF‐T of beef reached over 20% and 1.5‐fold with 5.22 log CFU/g aerobic bacteria, which was lesser than the Korean regulation value of 6.7 log CFU/g (5 × 106 CFU/g). Therefore, RF‐T could be proposed as a promising high‐temperature tenderization method with lowered risk of microbial spoilage. Practical Application: We showed that lowering the chamber temperature during RF‐T was effective in surface drying and inhibiting aerobic bacteria. RF‐T for 24–48 h with 30 W/kg specific RF heating power had an aging‐like effect given tenderization and increase in FAAs. Moreover, by providing the matching circuit and impedance during RF‐T, this method could be industrially reproducible. [ABSTRACT FROM AUTHOR]

Initial based disambiguation of author names is a common data pre-processing step in bibliometrics. It is widely accepted that this procedure can introduce errors into network data and any subsequent analytical results. What is not sufficiently understood is the precise impact of this step on the data and findings. We present an empirical answer to this question by comparing the impact of two commonly used initial based disambiguation methods against a reasonable proxy for ground truth data. We use DBLP, a database covering major journals and conferences in computer science and information science, as a source. We find that initial based disambiguation induces strong distortions in network metrics on the graph and node level: Authors become embedded in ties for which there is no empirical support, thus increasing their sphere of influence and diversity of involvement. Consequently, networks generated with initial-based disambiguation are more coherent and interconnected than the actual underlying networks, and individual authors appear to be more productive and more strongly embedded than they actually are.