Oncogenic Function of DACT1 in Colon Cancer through the Regulation of β-catenin

The Wnt/β-catenin signaling pathway plays important roles in the progression of colon cancer. DACT1 has been identified as a modulator of Wnt signaling through its interaction with Dishevelled (Dvl), a central mediator of both the canonical and noncanonical Wnt pathways. However, the functions of DACT1 in the WNT/β-catenin signaling pathway remain unclear. Here, we present evidence that DACT1 is an important positive regulator in colon cancer through regulating the stability and sublocation of β-catenin. We have shown that DACT1 promotes cancer cell proliferation in vitro and tumor growth in vivo and enhances the migratory and invasive potential of colon cancer cells. Furthermore, the higher expression of DACT1 not only increases the nuclear and cytoplasmic fractions of β-catenin, but also increases its membrane-associated fraction. The overexpression of DACT1 leads to the increased accumulation of nonphosphorylated β-catenin in the cytoplasm and particularly in the nuclei. We have demonstrated that DACT1 interacts with GSK-3β and β-catenin. DACT1 stabilizes β-catenin via DACT1-induced effects on GSK-3β and directly interacts with β-catenin proteins. The level of phosphorylated GSK-3β at Ser9 is significantly increased following the elevated expression of DACT1. DACT1 mediates the subcellular localization of β-catenin via increasing the level of phosphorylated GSK-3β at Ser9 to inhibit the activity of GSK-3β. Taken together, our study identifies DACT1 as an important positive regulator in colon cancer and suggests a potential strategy for the therapeutic control of the β-catenin-dependent pathway

Failure Evaluation of Bridge Deck Based on Parallel Connection Bayesian Network: Analytical Model

Failure is a major element that causes deterioration, which in turn affects the serviceability of long span bridges. Currently, the Bayesian network, which relates to probability statistics, is widely used for evaluating fatigue failure reliability. In particular, Bayesian network can not only calculate the fatigue failure at the system level, but also deduce the fatigue failure at the weld level. In this study, a system-level fatigue reliability evaluation model of a bridge deck (BD), which is seen as a parallel system, is proposed based on the Bayesian network. A fatigue probability reliability model of the BD was derived using the master S-N curve. In addition, the Monte Carlo (MC) method was applied to solve the multi-dimensional and complex analytical expressions in the Bayesian network. The applicability of the proposed model was demonstrated by three numerical case studies

Imaging of the Upper Mantle Beneath Southeast Asia: Constrained by Teleseismic P-Wave Tomography

It is of great significance to construct a three-dimensional underground velocity model for the study of geodynamics and tectonic evolution. Southeast Asia has attracted much attention due to its complex structural features. In this paper, we collected relative travel time residuals data for 394 stations distributed in Southeast Asia from 2006 to 2019, and 14,011 seismic events were obtained. Then, teleseismic tomography was applied by using relative travel time residuals data to invert the velocity where the fast marching method (FMM) and subspace method were used for every iteration. A novel 3D P-wave velocity model beneath Southeast Asia down to 720 km was obtained using this approach. The tomographic results suggest that the southeastern Tibetan Plateau, the Philippines, Sumatra, and Java, and the deep part of Borneo exhibit high velocity anomalies, while low velocity anomalies were found in the deep part of the South China Sea (SCS) basin and in the shallow part of Borneo and areas near the subduction zone. High velocity anomalies can be correlated to subduction plates and stable land masses, while low velocity anomalies can be correlated to island arcs and upwelling of mantle material caused by subduction plates. We found a southward subducting high velocity body in the Nansha Trough, which was presumed to be a remnant of the subduction of the Dangerous Grounds into Borneo. It is further inferred that the Nansha Trough and the Dangerous Grounds belong to the same tectonic unit. According to the tomographic images, a high velocity body is located in the deep underground of Indochina–Natuna Island–Borneo–Palawan, depth range from 240 km to 660 km. The location of the high velocity body is consistent with the distribution range of the ophiolite belt, so we speculate that the high velocity body is the remnant of thee Proto-South China Sea (PSCS) and Paleo-Tethys. This paper conjectures that the PSCS was the southern branch of Paleo-Tethys and the gateway between Paleo-Tethys and the Paleo-Pacific Ocean. Due to the squeeze of the Australian plate, PSCS closed from west to east in a scissor style, and was eventually extinct under Borneo

RNA-seq of hypo- and hyper-salinity stress-response transcriptome in the liver of greater amberjack (Seriola dumerili) juveniles

Salinity is an important abiotic stress that has significant effects on the physiology and metabolism of marine fish. The greater amberjack (Seriola dumerili) is a large, fast-growing species with high commercial value in global aquaculture. To describe the molecular response of the greater amberjack liver to different salinity stresses, RNA-seq analysis was performed to identify the important genes and signaling pathways activated in response to salt stress. Greater amberjack juveniles were reared under different salinity stresses (20, 30, and 40 ppt) for 30 days to evaluate their tolerance, adaptability, and molecular responses. A total of 657 (426 up-regulated and 231 down-regulated) and 65 (17 up-regulated and 48 down-regulated) differentially expressed genes (DEGs) were identified in the group at 30 vs. 20 ppt and 30 vs. 40 ppt salinity, respectively. qPCR and transcriptomic analysis showed that salinity stress affected the expression of genes involved in lipid metabolism (pld2, pla2g7, acacb, and acsl4a), vitamin metabolism (cyp24a1 and cyp2r1), ion transporters (slc4a1a, slc4a4b, rhag, and rh50), and signal transduction (itpkcb, fgf19, and fgfr4). KEGG pathway enrichment analysis showed that the DEGs were primarily involved in metabolism, ribosome biogenesis in eukaryotes, and insulin signaling pathway. The identified candidate genes involved in metabolism pathways, ion transporters, and signal transduction, provide a basis for further study of the molecular mechanisms involved in salinity adaptation and transcriptional plasticity in the livers of marine fish

SiGra: single-cell spatial elucidation through an image-augmented graph transformer

Abstract Recent advances in high-throughput molecular imaging have pushed spatial transcriptomics technologies to subcellular resolution, which surpasses the limitations of both single-cell RNA-seq and array-based spatial profiling. The multichannel immunohistochemistry images in such data provide rich information on the cell types, functions, and morphologies of cellular compartments. In this work, we developed a method, single-cell spatial elucidation through image-augmented Graph transformer (SiGra), to leverage such imaging information for revealing spatial domains and enhancing substantially sparse and noisy transcriptomics data. SiGra applies hybrid graph transformers over a single-cell spatial graph. SiGra outperforms state-of-the-art methods on both single-cell and spot-level spatial transcriptomics data from complex tissues. The inclusion of immunohistochemistry images improves the model performance by 37% (95% CI: 27–50%). SiGra improves the characterization of intratumor heterogeneity and intercellular communication and recovers the known microscopic anatomy. Overall, SiGra effectively integrates different spatial modality data to gain deep insights into spatial cellular ecosystems