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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
SYNOPSIS
Exercise significantly alters the DNA methylation profile of skeletal muscle, yet little is known about the underlying function of the DNA methylation machinery during exercise performance. Skeletal muscle DNA methyltransferase 3 (DNMT3) is necessary to maintain mitochondrial function and oxidative capacity, and support endurance exercise by suppressing Aldh1l1 transcription.
DNMT3A expression is increased in the oxidative soleus muscle during exercise.
Muscle‐specific Dnmt3a knockout mice display a reduced tolerance to endurance exercise.
Dnmt3a knockout soleus muscle overproduces ROS and exhibits mitochondrial dysfunction.
Aldh1l1 is a direct target gene of DNMT3A mediating mitochondrial dysfunction in red oxidative muscle.
Aldh1l1 knockdown partially restores exercise intolerance of Dnmt3a knockout mice.
Skeletal muscle‐expressed DNA methyltransferase 3 maintains mitochondrial function and oxidative capacity by suppressing Aldh1l1 transcription.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The supercooling degree (SD), which refers to the difference between the ice nucleation temperature and freezing point of kimchi, varies depending on the type of kimchi, manufacturer, recipe, and ...manufacturing season. The aim of this study is to investigate the major influencing factors for the supercooled storage of kimchi and to analyze the possibility of supercooled storage for commercial kimchi. Pearson correlation analysis determined that, in commercial kimchi manufactured between March and July 2018, the SD of kimchi correlated to the number of aerobic bacteria (P < 0.01), however, was not associated with lactic acid bacteria. Moreover, the ice nucleation temperature of saline solution inoculated with aerobic bacteria was reduced from –3.03 ± 0.04 to –6.18 ± 0.11 °C by 10 kGy gamma ray sterilization. Meanwhile, the ice nucleation temperatures of 1.8 kg of commercial red cabbage kimchi and 500 g of white cabbage kimchi manufactured in February 2020 were –3.93 ± 0.06 °C and −3.57 ± 0.06 °C, respectively, and they could be stored at –2.5 °C for 12 weeks without freezing. Additionally, supercooled storage of kimchi at –2.5 °C caused a fermentation delay effect compared to control storage at 1 °C, considering the acidity and amount of lactic acid bacteria. Therefore, if the number of aerobic bacteria is controlled during the manufacturing process of kimchi, supercooled storage at temperatures below −2.5 °C may extend the shelf life of kimchi.
Practical Application
We have shown that aerobic bacteria are the key influencing factor for ice nucleation of kimchi during supercooled storage. Aside from the initial sterilization process, fermentation of kimchi can also be delayed by lowering the storage temperature below −2.5 °C. Moreover, the method of direct cool refrigeration may have an industrial‐level application.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
With the emergence of large-language models (LLM) and generative AI, which require an enormous amount of model parameters, the required memory bandwidth and capacity for high-end systems is on an ...unprecedented increase. To meet this need, we present an extended version of the high-bandwidth memory-3 (HBM3 DRAM), HBM3E, which achieves a 1280GB/s bandwidth with a cube density of 48GB. New design schemes and features, such as all-around power-through-silicon via (TSV), a 6-phase read-data-strobe (RDQS) scheme, a byte-mapping swap scheme, and a voltage-drift compensator for write data strobe (WDQS), are implemented to achieve extended bandwidth and capacity with enhanced reliability. The overall architecture and specifications, such as bump map footprint, the number of channel and I/Os, and the operation voltage, are identical to the latest HBM3 1, 2; therefore, backward compatibility is provided, avoiding system modification.
This study investigated the comparative effectiveness of Christian devotional meditation (CDM) versus progressive muscle relaxation (PMR) on stress, anxiety, depression, and overall spiritual health ...among a sample of nonclinical Korean Christian adults in the United States. Seventy nine individuals at two churches in the northern Virginia area completed the study. At each church, the subjects were randomly assigned to a two-hour session of CDM training or PMR training. Each participant then was asked to practice the technique at home at least once a day for two weeks with audio recorded instructions. The participants' perceived level of stress, anxiety, depression, and spiritual health were assessed pre- and post-training. The results of the study revealed that while both practices were efficacious in decreasing anxiety and depression, CDM was statistically more efficacious. In addition, only the CDM group showed significant reductions in stress level and improved spiritual health. Participants also appeared to practice CDM more than PMR, suggesting CDM may be a culturally appropriate adaptation in counseling to encourage treatment compliance.
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