FGF signaling regulates Wnt ligand expression to control vulval cell lineage polarity in C. elegans

The interpretation of extracellular cues leading to the polarization of intracellular components and asymmetric cell divisions is a fundamental part of metazoan organogenesis. The Caenorhabditis elegans vulva, with its invariant cell lineage and interaction of multiple cell signaling pathways, provides an excellent model for the study of cell polarity within an organized epithelial tissue. Here, we show that the fibroblast growth factor (FGF) pathway acts in concert with the Frizzled homolog LIN-17 to influence the localization of SYS-1, a component of the Wnt/β-catenin asymmetry pathway, indirectly through the regulation of cwn-1. The source of the FGF ligand is the primary vulval precursor cell (VPC) P6.p, which controls the orientation of the neighboring secondary VPC P7.p by signaling through the sex myoblasts (SMs), activating the FGF pathway. The Wnt CWN-1 is expressed in the posterior body wall muscle of the worm as well as in the SMs, making it the only Wnt expressed on the posterior and anterior sides of P7.p at the time of the polarity decision. Both sources of cwn-1 act instructively to influence P7.p polarity in the direction of the highest Wnt signal. Using single molecule fluorescence in situ hybridization, we show that the FGF pathway regulates the expression of cwn-1 in the SMs. These results demonstrate an interaction between FGF and Wnt in C. elegans development and vulval cell lineage polarity, and highlight the promiscuous nature of Wnts and the importance of Wnt gradient directionality within C. elegans

Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Stanniocalcin-1(STC-1) is up-regulated in several cancers including gastric cancer. Evidences suggest that STC-1 is associated with carcinogenesis and angiogenic process. However, it is unclear on the exact role for STC-1 in inducing angiogenesis and tumorigeneisis.</p> <p>Method</p> <p>BGC/STC cells (high-expression of STC-1) and BGC/shSTC cells (low- expression of STC-1) were constructed to investigate the effect of STC-1 on the xenograft tumor growth and angiogenesis <it>in vitro </it>and <it>in vivo</it>. ELISA assay was used to detect the expression of vascular endothelial growth factor (VEGF) in the supernatants. Neutralizing antibody was used to inhibit VEGF expression in supernatants. The expression of phosphorylated -PKCβII, phosphorylated -ERK1/2 and phosphorylated -P38 in the BGC treated with STC-1protein was detected by western blot.</p> <p>Results</p> <p>STC-1 could promote angiogenesis <it>in vitro </it>and <it>in vivo</it>, and the angiogenesis was consistent with VEGF expression <it>in vitro</it>. Inhibition of VEGF expression in supernatants with neutralizing antibody markedly abolished angiogenesis induced by STC-1 <it>in vitro</it>. The process of STC-1-regulated VEGF expression was mediated via PKCβII and ERK1/2.</p> <p>Conclusions</p> <p>STC-1 promotes the expression of VEGF depended on the activation of PKCβII and ERK1/2 pathways. VEGF subsequently enhances tumor angiogenesis which in turn promotes the gastric tumor growth.</p

p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell

BACKGROUND: Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. RNA activation (RNAa) is a transcriptional activation phenomena guided by double-strand RNA (dsRNA) targeting promoter region of target gene. METHODS: In this study, we explored the effect of up-regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung carcinoma cells by transfecting the dsRNA targeting the promoter region of p21 into A549 cells. RESULTS: Enhanced p21 expression was observed in A549 cells after transfection of dsRNA, which was correlated with a significant growth inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter region of p21 could significantly inhibit A549 xenograft tumor growth. CONCLUSIONS: These results indicate that p21 plays a role in lung cancer drug-resistance process. In addition, this study also provides evidence for the usage of saRNA as a therapeutic option for up-regulating lower-expression genes in lung cancer

Source-independent elastic envelope inversion using the convolution method

Elastic full waveform inversion (EFWI) is a powerful technique. However, its strong non-linearity makes it susceptible to converging towards local extremes during the iterative process due to various factors like insufficient low-frequency information or an inadequate initial model. The existing elastic envelope inversion can offer a promising initial model for EFWI when low-frequency information is unavailable, reducing the dependence on both the initial model and low-frequency data. However, its accuracy is affected by the quality of the source wavelet, potentially causing the EFWI to run in the wrong direction if there is a discrepancy between the simulated wavelet and the field wavelet. To address these issues and enhance the reconstruction of large-scale information in the model, we propose a novel approach called source-independent elastic envelope inversion, employing the convolution method. By combining this method with source-independent multiscale EFWI, we effectively establish P- and S-wave velocity models even in situations with inaccurate wavelet information. The results of testing on a portion of the Marmousi2 model demonstrate the effectiveness of this technique for both full-band and low-frequency missing data scenarios

Ultrafast Dynamics of Flavins in Five Redox States

We report here our systematic studies of excited-state dynamics of two common flavin molecules, FMN and FAD, in five redox states of oxidized form, neutral and anionic semiquinones, and neutral and anionic fully-reduced hydroquinones in solution and in inert protein environments with femtosecond resolution. Using protein environments, we are able to stabilize two semiquinone radicals and thus observed their weak emission spectra. Significantly, we observed a strong correlation between their excited-state dynamics and the planarity of their flavin isoalloxazine ring. For a bent ring structure, we all observed ultrafast dynamics from a few to hundreds of picoseconds and strong excitation-wavelength dependence of emission spectra, indicating deactivation during relaxation. A butterfly bending motion is invoked to get access to conical intersection(s) to facilitate deactivation. These states include the anionic semiquinone radical and fully-reduced neutral and anionic hydroquinones in solution. In a planar configuration, flavins have a long lifetime in nanoseconds except for the stacked conformation of FAD, where the intramolecular electron transfer between the ring and the adenine moiety in 5-9 ps as well as the subsequent charge recombination in 30-40 ps were observed. These observed distinct dynamics, controlled by the flavin ring flexibility, are fundamental to flavoenzyme’s functions as observed in photolyase with a planar structure to lengthen the lifetime to maximize DNA repair efficiency and in insect Type 1 cryptochrome with a flexible structure to vary the excited-state deactivation to modulate the functional channel