Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three ...lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.
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IJS, NUK, SBMB, UL, UM, UPUK
Increasing the image size of a video sequence aggravates the memory bandwidth problem of a video coding system. Despite many embedded compression (EC) algorithms proposed to overcome this problem, no ...lossless EC algorithm able to handle high-definition (HD) size video sequences has been proposed thus far. In this paper, a lossless EC algorithm for HD video sequences and related hardware architecture is proposed. The proposed algorithm consists of two steps. The first is a hierarchical prediction method based on pixel averaging and copying. The second step involves significant bit truncation (SBT) which encodes prediction errors in a group with the same number of bits so that the multiple prediction errors are decoded in a clock cycle. The theoretical lower bound of the compression ratio of the SBT coding was also derived. Experimental results have shown a 60% reduction of memory bandwidth on average. Hardware implementation results have shown that a throughput of 14.2 pixels/cycle can be achieved with 36 K gates, which is sufficient to handle HD-size video sequences in real time.
Plant secondary metabolites (SMs) play important roles in plant survival and in creating ecological connections between other species. In addition to providing a variety of valuable natural products, ...secondary metabolites help protect plants against pathogenic attacks and environmental stresses. Given their sessile nature, plants must protect themselves from such situations through accumulation of these bioactive compounds. Indeed, secondary metabolites act as herbivore deterrents, barriers against pathogen invasion, and mitigators of oxidative stress. The accumulation of SMs are highly dependent on environmental factors such as light, temperature, soil water, soil fertility, and salinity. For most plants, a change in an individual environmental factor can alter the content of secondary metabolites even if other factors remain constant. In this review, we focus on how individual environmental factors affect the accumulation of secondary metabolites in plants during both biotic and abiotic stress conditions. Furthermore, we discuss the application of abiotic and biotic elicitors in culture systems as well as their stimulating effects on the accumulation of secondary metabolites. Specifically, we discuss the shikimate pathway and the aromatic amino acids produced in this pathway, which are the precursors of a range of secondary metabolites including terpenoids, alkaloids, and sulfur- and nitrogen-containing compounds. We also detail how the biosynthesis of important metabolites is altered by several genes related to secondary metabolite biosynthesis pathways. Genes responsible for secondary metabolite biosynthesis in various plant species during stress conditions are regulated by transcriptional factors such as WRKY, MYB, AP2/ERF, bZIP, bHLH, and NAC, which are also discussed here.
Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and ...physiological effect between IBD patients with (IBD/D
) or without depression (IBD/D
), we analyzed the fecal microbiota composition of patients with IBD with (/D
) or without depression (/D
) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D
or IBD/D
caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB
/CD11c
cell population in the colon. Transplantation of the IBD/D
patient feces (IBD/D
-F) caused IBD-like colitis more strongly than that of IBD/D
-F. FMTs from patients with IBD/D
also caused anxiety-/depression-like behaviors, increased the NF-κB
/Iba1
and lipopolysaccharide (LPS)
/Iba1
cell populations, and decreased the BDNF
/NeuN
cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D
caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D
-F vs. IBD/D
-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D
-F significantly reduced depression-like behaviors, NF-κB
/Iba1
and LPS
/Iba1
cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.
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Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of ...migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 4.0-7.0 vs. 5.0 3.0-6.0, p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.
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Although tetraarsenic hexoxide is known to exert an anti-tumor effect by inducing apoptosis in various cancer cells, its effect on other forms of regulated cell death remains unclear. Here, we show ...that tetraarsenic hexoxide induces the pyroptotic cell death through activation of mitochondrial reactive oxygen species (ROS)-mediated caspase-3/gasdermin E (GSDME) pathway, thereby suppressing tumor growth and metastasis of triple-negative breast cancer (TNBC) cells. Interestingly, tetraarsenic hexoxide-treated TNBC cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling, and LDH releases through pore formation in the plasma membrane, eventually suppressing tumor formation and lung metastasis of TNBC cells. Mechanistically, tetraarsenic hexoxide markedly enhanced the production of mitochondrial ROS by inhibiting phosphorylation of mitochondrial STAT3, subsequently inducing caspase-3-dependent cleavage of GSDME, which consequently promoted pyroptotic cell death in TNBC cells. Collectively, our findings highlight tetraarsenic hexoxide-induced pyroptosis as a new therapeutic strategy that may inhibit cancer progression of TNBC cells.
Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee ...consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.
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A 48 WL stacked 256-Gb V-NAND flash memory with a 3 b MLC technology is presented. Several vertical scale-down effects such as deteriorated WL loading and variations are discussed. To enhance ...performance, reverse read scheme and variable-pulse scheme are presented to cope with nonuniform WL characteristics. For improved performance, dual state machine architecture is proposed to achieve optimal timing for BL and WL, respectively. Also, to maintain robust IO driver strength against PVT variations, an embedded ZQ calibration technique with temperature compensation is introduced. The chip, fabricated in a third generation of V-NAND technology, achieved a density of 2.6 Gb/mm 2 with 53.2 MB/s of program throughput.
Information on sex differences in the association between chronotype and depression is scarce. We aimed to investigate these differences using data from the Korea National Health and Nutrition ...Examination Survey in 2016. Chronotypes were categorised based on mid-sleep time on free days corrected by sleep debt accumulated on workdays (MSFsc): early type, < mean MSFsc - 1 standard deviation (SD); intermediate type, between mean MSFsc - 1 SD and MSFsc + 1 SD; and late type, > mean MSFsc + 1 SD. A Patient Health Questionnaire-9 score of ≥ 10 indicated depression. Among 5550 non-shift working adults aged 19-80 years, the prevalence rates of depression in the early, intermediate, and late chronotype groups were 7.4%, 4.5%, and 9.3%, respectively. Women with late chronotype (odds ratio OR = 2.9, 95% confidence interval CI = 1.8-4.7) showed a higher risk of depression than women with intermediate chronotype after adjusting for covariates. Women with early chronotype did not show a significant difference in depression risk (OR = 1.3, 95% CI = 0.9-2.0). In conclusion, late chronotype is associated with an increased risk of depression in women but not in men. Early chronotype is not associated with depression in women or men.
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