KHAN: Knowledge-Aware Hierarchical Attention Networks for Accurate Political Stance Prediction

The political stance prediction for news articles has been widely studied to mitigate the echo chamber effect -- people fall into their thoughts and reinforce their pre-existing beliefs. The previous works for the political stance problem focus on (1) identifying political factors that could reflect the political stance of a news article and (2) capturing those factors effectively. Despite their empirical successes, they are not sufficiently justified in terms of how effective their identified factors are in the political stance prediction. Motivated by this, in this work, we conduct a user study to investigate important factors in political stance prediction, and observe that the context and tone of a news article (implicit) and external knowledge for real-world entities appearing in the article (explicit) are important in determining its political stance. Based on this observation, we propose a novel knowledge-aware approach to political stance prediction (KHAN), employing (1) hierarchical attention networks (HAN) to learn the relationships among words and sentences in three different levels and (2) knowledge encoding (KE) to incorporate external knowledge for real-world entities into the process of political stance prediction. Also, to take into account the subtle and important difference between opposite political stances, we build two independent political knowledge graphs (KG) (i.e., KG-lib and KG-con) by ourselves and learn to fuse the different political knowledge. Through extensive evaluations on three real-world datasets, we demonstrate the superiority of DASH in terms of (1) accuracy, (2) efficiency, and (3) effectiveness.Comment: 12 pages, 5 figures, 10 tables, the Web Conference 2023 (WWW

Cross-Regulation between Oncogenic BRAFV600E Kinase and the MST1 Pathway in Papillary Thyroid Carcinoma

BACKGROUND:The BRAF(V600E) mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A methylation, the regulatory mechanisms of RASSF1A-MST1 pathways remain to be elucidated, and the functional cooperation or cross regulation between BRAF(V600E) and MST1,which activates Foxo3,has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS:The negative regulators of the cell cycle, p21 and p27, are strongly induced by transcriptional activation of FoxO3 in BRAF(V600E) positive thyroid cancer cells. The FoxO3 transactivation is augmented by RASSF1A and the MST1 signaling pathway. Interestingly, introduction of BRAF(V600E)markedly abolished FoxO3 transactivation and resulted in the suppression of p21 and p27 expression. The suppression of FoxO3 transactivation by BRAF(V600E)is strongly increased by coexpression of MST1 but it is not observed in the cells in which MST1, but not MST2,is silenced. Mechanistically, BRAF(V600E)was able to bind to the C-terminal region of MST1 and resulted in the suppression of MST1 kinase activities. The induction of the G1-checkpoint CDK inhibitors, p21 and p27,by the RASSF1A-MST1-FoxO3 pathway facilitates cellular apoptosis, whereas addition of BRAF(V600E) inhibits the apoptotic processes through the inactivation of MST1. Transgenic induction of BRAF(V600E)in the thyroid gland results in cancers resembling human papillary thyroid cancers. The development of BRAF(V600E)transgenic mice with the MST1 knockout background showed that these mice had abundant foci of poorly differentiated carcinomas and large areas without follicular architecture or colloid formation. CONCLUSIONS/SIGNIFICANCE:The results of this study revealed that the oncogenic effect of BRAF(V600E) is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF(V600E) tumors

Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures

Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2' insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains. DNA aptamers can activate insulin receptor as selective agonists or positive allosteric modulators. Here, authors determine structures of the insulin receptor bound to aptamers and provide a basis for the selective activation or allosteric regulation of insulin receptor.11Ysciescopu

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.Y

Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16INK4a-Negative Cancer

Although abnormal increases in the level or activity of cyclin-dependent kinase 4 (CDK4) occur frequently in cancer, the underlying mechanism is not fully understood. Here, we show that methionyl-tRNA synthetase (MRS) specifically stabilizes CDK4 by enhancing the formation of the complex between CDK4 and a chaperone protein. Knockdown of MRS reduced the CDK4 level, resulting in G0/G1 cell cycle arrest. The effects of MRS on CDK4 stability were more prominent in the tumor suppressor p16INK4a-negative cancer cells because of the competitive relationship of the two proteins for binding to CDK4. Suppression of MRS reduced cell transformation and the tumorigenic ability of a p16INK4a-negative breast cancer cell line in vivo. Further, the MRS levels showed a positive correlation with those of CDK4 and the downstream signals at high frequency in p16INK4a-negative human breast cancer tissues. This work revealed an unexpected functional connection between the two enzymes involving protein synthesis and the cell cycle

Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16^INK4a-Negative Cancer

Although abnormal increases in the level or activity of cyclin-dependent kinase 4 (CDK4) occur frequently in cancer, the underlying mechanism is not fully understood. Here, we show that methionyl-tRNA synthetase (MRS) specifically stabilizes CDK4 by enhancing the formation of the complex between CDK4 and a chaperone protein. Knockdown of MRS reduced the CDK4 level, resulting in G0/G1 cell cycle arrest. The effects of MRS on CDK4 stability were more prominent in the tumor suppressor p16^INK4a-negative cancer cells because of the competitive relationship of the two proteins for binding to CDK4. Suppression of MRS reduced cell transformation and the tumorigenic ability of a p16^INK4a-negative breast cancer cell line <i>in vivo</i>. Further, the MRS levels showed a positive correlation with those of CDK4 and the downstream signals at high frequency in p16^INK4a-negative human breast cancer tissues. This work revealed an unexpected functional connection between the two enzymes involving protein synthesis and the cell cycle