Epigenetic Regulation of KPC1 Ubiquitin Ligase Affects the NF-κB Pathway in Melanoma.

Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA cohort, n = 370). Using melanoma cell lines, we investigated the functional interactions between KPC1 and NF-κB, and the epigenetic regulations of KPC1, including DNA methylation and miRNA expression.Results: We verified that KPC1 suppresses melanoma proliferation by processing NF-κB1 p105 into p50, thereby modulating NF-κB target gene expression. Concordantly, KPC1 expression was downregulated in American Joint Committee on Cancer stage IV melanoma compared with early stages (stage I/II P = 0.013, stage III P = 0.004), and low KPC1 expression was significantly associated with poor overall survival in stage IV melanoma (n = 137; HR 1.810; P = 0.006). Furthermore, our data showed that high miR-155-5p expression, which is controlled by DNA methylation at its promoter region (TCGA; Pearson\u27s r -0.455; P \u3c 0.001), is significantly associated with KPC1 downregulation (JWCI; P = 0.028, TCGA; P = 0.003).Conclusions: This study revealed novel epigenetic regulation of KPC1 associated with NF-κB pathway activation, promoting metastatic melanoma progression. These findings suggest the potential utility of KPC1 and its epigenetic regulation as theranostic targets. Clin Cancer Res; 23(16); 4831-42. ©2017 AACR

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Sulfur and Nitrogen Distributions during Coal Carbonization and the Influences of These Elements on Coal Fluidity and Coke Strength

The present study focuses on examining the fate of coal-S and coal-N during carbonization in detail and making clear the effects of these elements on coal fluidity and coke strength. When eight kinds of caking coals with 80–88 mass%-daf C are carbonized in high-purity He at 3°C/min up to 1000°C with a quartz-made fixed bed reactor, 50–75% of coal-S remains as FeS and organic-S in the coke, and the rest is released as tar-S and H2S. Most of coal-N is also retained in the coke, and the remainder is converted to tar-N, HCN, NH3 and N2. The eight coals give Gieseler maximum fluidity values between 435 and 480°C, and the value tends to be larger at a smaller sulfur content in coal or in the carbonaceous material recovered after carbonization at 450°C. It also seems that the value increases with increasing nitrogen content in coal or total amount of either HCN or NH3 formed up to 450°C. Furthermore, the addition of S-containing compounds to an Australian bituminous coal lowers coal fluidity and coke strength considerably, whereas indole gives the reverse effect on them. On the basis of these results, it is suggested that coal-S or some coal-N has a negative or positive effect on the two properties, respectively

AMoND: Area-Controlled Mobile Ad-Hoc Networking With Digital Twin

Future smart cities are expected to provide intelligent services such as predictions, detections, and automation through digital twins. However, the creation of digital twins requires the processing of an enormous amount of data, thereby leading to an increase in mobile network traffic. This traffic is produced by applications in user devices and city services, which engage in local consumption at the city scale through sensor and camera devices using mobile networks. Such increased traffic can compromise the communication speed and stability. To alleviate this burden, traffic offloading becomes a crucial consideration in the beyond-5G era. This paper presents a scheme known as Area-Controlled Mobile Ad-Hoc Networking (AMoND). AMoND uses a hierarchical structure of a location layer and an ad-hoc layer to construct area-controlled mobile ad-hoc networks (MANETs) for mutual support of the digital twin and MANETs. AMoND effectively suppresses mobile network traffic by harnessing the digital twin to assist the MANETs during data collection for the digital twin construction. Importantly, the digital twin used in AMoND focuses on the management of node location information and does not need to reproduce the real space on a computer fully. AMoND is not dependent on a specific MANET protocol and can be used as an add-on. AMoND exhibits the ability to reduce traffic volumes by up to approximately 65%, while maintaining arrival rates that are comparable to existing MANET protocols under certain conditions

Sulfur and Nitrogen Distributions during Coal Carbonization and the Influences of These Elements on Coal Fluidity and Coke Strength

The present study focuses on examining the fate of coal-S and coal-N during carbonization in detail and making clear the effects of these elements on coal fluidity and coke strength. When eight kinds of caking coals with 80–88 mass%-daf C are carbonized in high-purity He at 3°C/min up to 1000°C with a quartz-made fixed bed reactor, 50–75% of coal-S remains as FeS and organic-S in the coke, and the rest is released as tar-S and H2S. Most of coal-N is also retained in the coke, and the remainder is converted to tar-N, HCN, NH3 and N2. The eight coals give Gieseler maximum fluidity values between 435 and 480°C, and the value tends to be larger at a smaller sulfur content in coal or in the carbonaceous material recovered after carbonization at 450°C. It also seems that the value increases with increasing nitrogen content in coal or total amount of either HCN or NH3 formed up to 450°C. Furthermore, the addition of S-containing compounds to an Australian bituminous coal lowers coal fluidity and coke strength considerably, whereas indole gives the reverse effect on them. On the basis of these results, it is suggested that coal-S or some coal-N has a negative or positive effect on the two properties, respectively