Estrogen regulates Hippo signaling via GPER in breast cancer

The G protein–coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis

Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines

Efficient keyword search on uncertain graph data

As a popular search mechanism, keyword search has been applied to retrieve useful data in documents, texts, graphs, and even relational databases. However, so far, there is no work on keyword search over uncertain graph data even though the uncertain graphs have been widely used in many real applications, such as modeling road networks, influential detection in social networks, and data analysis on PPI networks. Therefore, in this paper, we study the problem of top-k keyword search over uncertain graph data. Following the similar answer definition for keyword search over deterministic graphs, we consider a subtree in the uncertain graph as an answer to a keyword query if 1) it contains all the keywords; 2) it has a high score (defined by users or applications) based on keyword matching; and 3) it has low uncertainty. Keyword search over deterministic graphs is already a hard problem as stated in [1], [2], [3]. Due to the existence of uncertainty, keyword search over uncertain graphs is much harder. Therefore, to improve the search efficiency, we employ a filtering-and-verification strategy based on a probabilistic keyword index, PKIndex. For each keyword, we offline compute path-based top-k probabilities, and attach these values to PKIndex in an optimal, compressed way. In the filtering phase, we perform existence, path-based and tree-based probabilistic pruning phases, which filter out most false subtrees. In the verification, we propose a sampling algorithm to verify the candidates. Extensive experimental results demonstrate the effectiveness of the proposed algorithms. © 1989-2012 IEEE

H2A.Z acetylation by lincZNF337-AS1 via KAT5 implicated in the transcriptional misregulation in cancer signaling pathway in hepatocellular carcinoma

Abstract In eukaryotes, histones and their variants are essential for chromatin structure and function; both play important roles in the regulation of gene transcription, as well as the development of tumors. We aimed to explore the genomics data of hepatocellular carcinoma (HCC), combined with literature analysis, in terms of the histone variant H2A.Z. Cell phenotype assay confirmed the effect of H2A.Z on the proliferation, metastasis, apoptosis, and cell cycle of HCC cells. H2A.Z was shown to function via the tumor dysregulation signaling pathway, with BCL6 as its interacting protein. In addition, the acetylation level of H2A.Z was higher in HCC and was related to tumor formation. We found the acetylation of H2A.Z to be related to and regulated by lincZNF337-AS1. LincZNF337-AS1 was found to bind to H2A.Z and KAT5 at different sites, promoting the acetylation of H2A.Z through KAT5. We concluded that, in HCC, H2A.Z is an oncogene, whose acetylation promotes the transcription of downstream genes, and is regulated by lincZNF331-AS1

RNN-Assisted Feature-Extraction VMD for Load Classification in Cloud Computing Platform

Cloud computing can improve the calculation and data storage ability for the control center in the power system. A new framework of the cloud-based control center is proposed in this paper. This cloud computing system can collect the load data from smart meters of the grid and classify demand-side management (DSM) loads that meet the specific requirements. The selected loads belong to the off-peak period (from 21:00 to 07:00 next day) and can contribute to shifting the night peak load. A feature extraction combined with Variational Mode Decomposition (FE-VMD) of the loads which can be trained in recurrent neural network (RNN) is proposed in this paper. Using the feature value to replace the actual load data, input data can be significantly reduced which is suitable for a vast amount of load in the power system. A case study of real load data from 200,000 customers has been classified with this method, and the accuracy is compared with the other methods. From simulation with MATLAB, it can be seen that the FE-VMD combined with the RNN method provides the best result of 89.8% recognition accuracy among these methods.</p

Prognostic biomarker tumor-infiltrating lymphocytes failed to serve as a predictive biomarker for postoperative radiotherapy in completely resected pN2 non-small cell lung cancer: a retrospective analysis

Abstract Background Evidence suggests that radiotherapy is a potent immunomodulator in non-small cell lung cancer (NSCLC). Conversely, it has rarely been demonstrated if immune infiltration can influence radiotherapy efficacy. Herein, we explored the effect of tumor-infiltrating lymphocytes (TILs) on the response to postoperative radiotherapy (PORT) in completely resected stage III-pN2 NSCLC. Methods This retrospective study included 244 patients with pathologically confirmed stage III-N2 NSCLC who underwent complete resection at our institution between 2014 and 2020. TILs were assessed with permanent full-face hematoxylin and eosin (H&E) sections and the evaluation of TILs was based on a published guideline. Patients were stratified into the TILlow or TILhigh group with a cutoff value of 50%. Kaplan-Meier method and Log‐rank test were utilized to assess disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression analysis were conducted to determine prognostic indicators. Results Among 244 patients, a total of 121 patients received PORT whereas 123 did not. TILs level in patients with PORT was significantly higher than that in patients without PORT (p < 0.001). High TILs level was significantly associated with an improved DFS and OS in all the entire chort (DFS, p < 0.001; OS, p = 0.001), PORT chort (DFS, p = 0.003; OS, p = 0.011) and non-PORT chort (DFS, p < 0.001; OS, p = 0.034). There were no significant survival differences between different treatment modalities in the low TILs infiltration (DFS, p = 0.244; OS, p = 0.404) and high TILs infiltration (DFS, p = 0.167; OS, p = 0.958) groups. Conclusions TILs evaluated with H&E sections could represent a prognostic biomarker in patients with completely resected pN2 NSCLC, and high TILs infiltration was associated with favorable survival outcomes.The predictive value of TILs for PORT still need to be further explored in the future