Histone lysine demethylase 3B (KDM3B) regulates the propagation of autophagy via transcriptional activation of autophagy-related genes.

Autophagy, a self-degradative physiological process, is critical for homeostasis maintenance and energy source balancing in response to various stresses, including nutrient deprivation. It is a highly conserved catabolic process in eukaryotes and is indispensable for cell survival as it involves degradation of unessential or excessive components and their subsequent recycling as building blocks for the synthesis of necessary molecules. Although the dysregulation of autophagy has been reported to broadly contribute to various diseases, including cancers and neurodegenerative diseases, the molecular mechanisms underlying the epigenetic regulation of autophagy are poorly elucidated. Here, we report that the level of lysine demethylase 3B (KDM3B) increases in nutrient-deprived HCT116 cells, a colorectal carcinoma cell line, resulting in transcriptional activation of the autophagy-inducing genes. KDM3B was found to enhance the transcription by demethylating H3K9me2 on the promoter of these genes. Furthermore, we observed that the depletion of KDM3B inhibited the autophagic flux in HCT116 cells. Collectively, these data suggested the critical role of KDM3B in the regulation of autophagy-related genes via H3K9me2 demethylation and induction of autophagy in nutrient-starved HCT116 cells

Web atmospheric qualities in luxury fashion brand web sites

Purpose – The purpose of this paper is to explore the relationship between atmospheric qualities with different levels of task relevance in luxury fashion brand web sites and their impact on consumer attitude toward the site and brand, which is essential to build valid strategies for e-retailing. Design/methodology/approach – An empirical study was conducted and quantitative analyses of 292 respondents shopping experiences yielded findings that confirm the impact of atmospherics upon the shoppers views of the web site and the brand. Structural equation modeling was used to test the research hypotheses. Findings – Both low task-relevant atmospherics (web site design, responsive customer service) and high task-relevant atmospherics (product information, convenience) affect the consumers revisit intentions toward the web site, while web site design directly affected brand attitude. The study also illustrates the mediating roles of product information and convenience to the relationships between web site design and responsive customer service and the consumers revisit intentions toward the site. Practical implications – This study provides insights for luxury e-tailing. Luxury e-tailers should understand the different effects depending upon the types of web atmospheric qualities and use them strategically. Originality/value – The main contribution of the study is to highlight the unique aspects of luxury online shopping in the Korean context. This study also contributes to e-commerce research by providing an expanded understanding of the interrelationship between types of web atmospheric qualitiesOAIID:oai:osos.snu.ac.kr:snu2015-01/102/0000008502/5ADJUST_YN:YEMP_ID:A074828DEPT_CD:353CITE_RATE:0DEPT_NM:의류학과CONFIRM:

Deacetylase activity-independent transcriptional activation by HDAC2 during TPA-induced HL-60 cell differentiation.

The human myeloid leukemia cell line HL-60 differentiate into monocytes following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the mechanism underlying the differentiation of these cells in response to TPA has not been fully elucidated. In this study, we performed ChIP-seq profiling of RNA Pol II, HDAC2, Acetyl H3 (AcH3), and H3K27me3 and analyzed differential chromatin state changes during TPA-induced differentiation of HL-60 cells. We focused on atypically active genes, which showed enhanced H3 acetylation despite increased HDAC2 recruitment. We found that HDAC2 positively regulates the expression of these genes in a histone deacetylase activity-independent manner. HDAC2 interacted with and recruited paired box 5 (PAX5) to the promoters of the target genes and regulated HL-60 cell differentiation by PAX5-mediated gene activation. Taken together, these data elucidated the specific-chromatin status during HL-60 cell differentiation following TPA exposure and suggested that HDAC2 can activate transcription of certain genes through interactions with PAX5 in a deacetylase activity-independent pathway

Enhancing Li Ion Battery Performance by Mechanical Resonance

© 2021 American Chemical Society.The quest for safe and high-performance Li ion batteries (LIBs) motivates intense efforts seeking a high-energy but reliable anode, cathode, and nonflammable electrolyte. For any of these, exploring new electrochemistry methods that enhance safety and performance by employing well-designed electrodes and electrolytes are required. Electrolyte wetting, governed by thermodynamics, is another critical issue in increasing Li ion transport through the separator. Herein, we report an approach to enhancing LIB performance by applying mechanical resonant vibration to increase electrolyte wettability on the separator. Wetting is activated at a resonant frequency with a capillary wave along the surface of the electrolyte, allowing the electrolyte to infiltrate into the porous separator by inertia force. This mechanical resonance, rather than electrochemistry, leads to the high specific capacity, rate capability, and cycling stability of LIBs. The concept of the mechanical approach is a promising yet simple strategy for the development of safer LIBs using liquid electrolytes.11Nsciescopu

Enhancing Li Ion Battery Performance by Mechanical Resonance

© 2021 American Chemical Society.The quest for safe and high-performance Li ion batteries (LIBs) motivates intense efforts seeking a high-energy but reliable anode, cathode, and nonflammable electrolyte. For any of these, exploring new electrochemistry methods that enhance safety and performance by employing well-designed electrodes and electrolytes are required. Electrolyte wetting, governed by thermodynamics, is another critical issue in increasing Li ion transport through the separator. Herein, we report an approach to enhancing LIB performance by applying mechanical resonant vibration to increase electrolyte wettability on the separator. Wetting is activated at a resonant frequency with a capillary wave along the surface of the electrolyte, allowing the electrolyte to infiltrate into the porous separator by inertia force. This mechanical resonance, rather than electrochemistry, leads to the high specific capacity, rate capability, and cycling stability of LIBs. The concept of the mechanical approach is a promising yet simple strategy for the development of safer LIBs using liquid electrolytes.11Nsciescopu

FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes.

RATIONALE: Vascular smooth muscle cells (SMCs) exhibit remarkable plasticity and can undergo dedifferentiation upon pathological stimuli associated with disease and interventions. OBJECTIVE: Although epigenetic changes are critical in SMC phenotype switching, a fundamental regulator that governs the epigenetic machineries regulating the fate of SMC phenotype has not been elucidated. METHODS AND RESULTS: Using SMCs, mouse models, and human atherosclerosis specimens, we found that FAK (focal adhesion kinase) activation elicits SMC dedifferentiation by stabilizing DNMT3A (DNA methyltransferase 3A). FAK in SMCs is activated in the cytoplasm upon serum stimulation in vitro or vessel injury and active FAK prevents DNMT3A from nuclear FAK-mediated degradation. However, pharmacological or genetic FAK catalytic inhibition forced FAK nuclear localization, which reduced DNMT3A protein via enhanced ubiquitination and proteasomal degradation. Reduced DNMT3A protein led to DNA hypomethylation in contractile gene promoters, which increased SMC contractile protein expression. RNA-sequencing identified SMC contractile genes as a foremost upregulated group by FAK inhibition from injured femoral artery samples compared with vehicle group. DNMT3A knockdown in injured arteries reduced DNA methylation and enhanced contractile gene expression supports the notion that nuclear FAK-mediated DNMT3A degradation via E3 ligase TRAF6 (TNF [tumor necrosis factor] receptor-associated factor 6) drives differentiation of SMCs. Furthermore, we observed that SMCs of human atherosclerotic lesions exhibited decreased nuclear FAK, which was associated with increased DNMT3A levels and decreased contractile gene expression. CONCLUSIONS: This study reveals that nuclear FAK induced by FAK catalytic inhibition specifically suppresses DNMT3A expression in injured vessels resulting in maintaining SMC differentiation by promoting the contractile gene expression. Thus, FAK inhibitors may provide a new treatment option to block SMC phenotypic switching during vascular remodeling and atherosclerosis

Nuclear Focal Adhesion Kinase Controls Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Through GATA4-Mediated Cyclin D1 Transcription

RationaleNeointimal hyperplasia is characterized by excessive accumulation of vascular smooth muscle cells (SMCs) leading to occlusive disorders, such as atherosclerosis and stenosis. Blood vessel injury increases growth factor secretion and matrix synthesis, which promotes SMC proliferation and neointimal hyperplasia via FAK (focal adhesion kinase).ObjectiveTo understand the mechanism of FAK action in SMC proliferation and neointimal hyperplasia.Methods and resultsUsing combined pharmacological FAK catalytic inhibition (VS-4718) and SMC-specific FAK kinase-dead (Myh11-Cre-ERT2) mouse models, we report that FAK regulates SMC proliferation and neointimal hyperplasia in part by governing GATA4- (GATA-binding protein 4) cyclin D1 signaling. Inhibition of FAK catalytic activity facilitates FAK nuclear localization, which is required for proteasome-mediated GATA4 degradation in the cytoplasm. Chromatin immunoprecipitation identified GATA4 binding to the mouse cyclin D1 promoter, and loss of GATA4-mediated cyclin D1 transcription diminished SMC proliferation. Stimulation with platelet-derived growth factor or serum activated FAK and redistributed FAK from the nucleus to cytoplasm, leading to concomitant increase in GATA4 protein and cyclin D1 expression. In a femoral artery wire injury model, increased neointimal hyperplasia was observed in parallel with elevated FAK activity, GATA4 and cyclin D1 expression following injury in control mice, but not in VS-4718-treated and SMC-specific FAK kinase-dead mice. Finally, lentiviral shGATA4 knockdown in the wire injury significantly reduced cyclin D1 expression, SMC proliferation, and neointimal hyperplasia compared with control mice.ConclusionsNuclear enrichment of FAK by inhibition of FAK catalytic activity during vessel injury blocks SMC proliferation and neointimal hyperplasia through regulation of GATA4-mediated cyclin D1 transcription