Numerical Analysis of Spreading Process of Ellipsoidal Spraying Droplet Impacting on Superhydrophobic Surface

Agricultural spray deposition is especially important for pesticide application because low efficiency can lead to environmental pollution, poor biological efficiency and economic loss. The deposition of pesticide spray on the leave surfaces is related to the impact kinetic behavior of droplets. But after considering the deformation of the droplet, how impingement will affect the deposition is an interesting research. In this study, a superhydrophobic surface was used to replace the plant surface that the pesticide droplets may affect. An interface tracking method was proposed to characterize the impingement dynamics behaviors of different ellipsoid droplets impacting on the surface. The maximum spreading coefficient and time of ellipsoidal droplets increased with the raise of their size. A lower sized droplet has a faster spreading rate, while the center of a higher sized droplet is thinner. As the velocity of pesticide increases, maximum spreading coefficient of droplet increases with a decrease in the maximum spreading time of droplet. The simulation results can contribute to provide theoretical basis for improving spray efficiency

Lsh Mediated RNA Polymerase II Stalling at HoxC6 and HoxC8 Involves DNA Methylation

DNA cytosine methylation is an important epigenetic mechanism that is involved in transcriptional silencing of developmental genes. Several molecular pathways have been described that interfere with Pol II initiation, but at individual genes the molecular mechanism of repression remains uncertain. Here, we study the molecular mechanism of transcriptional regulation at Hox genes in dependence of the epigenetic regulator Lsh that controls CpG methylation at selected Hox genes. Wild type cells show a nucleosomal deprived region around the transcriptional start site at methylated Hox genes and mediate gene silencing via Pol II stalling. Hypomethylation in Lsh−/− cells is associated with efficient transcriptional elongation and splicing, in part mediated by the chromodomain protein Chd1. Dynamic modulation of DNA methylation in Lsh−/− and wild type cells demonstrates that catalytically active DNA methyltransferase activity is required for Pol II stalling. Taken together, the data suggests that DNA methylation can be compatible with Pol II binding at selected genes and Pol II stalling can act as alternate mechanism to explain transcriptional silencing associated with DNA methylation

Inhibition of RNF182 mediated by Bap promotes non-small cell lung cancer progression

IntroductionUbiquitylation that mediated by ubiquitin ligases plays multiple roles not only in proteasome-mediated protein degradation but also in various cellular process including DNA repair, signal transduction and endocytosis. RING finger (RNF) proteins form the majority of these ubiquitin ligases. Recent studies have demonstrated the important roles of RNF finger proteins in tumorigenesis and tumor progression. Benzo[a]pyrene (BaP) is one of the most common environmental carcinogens causing lung cancer. The molecular mechanism of Bap carcinogenesis remains elusive. Considering the critical roles of RNF proteins in tumorigenesis and tumor progression, we speculate on whether Bap regulates RNF proteins resulting in carcinogenesis.MethodsWe used GEO analysis to identify the potential RING finger protein family member that contributes to Bap-induced NSCLC. We next used RT-qPCR, Western blot and ChIP assay to investigate the potential mechanism of Bap inhibits RNF182. BGS analyses were used to analyze the methylation level of RNF182.ResultsHere we reported that the carcinogen Bap suppresses the expression of ring finger protein 182 (RNF182) in non-small cell lung cancer (NSCLC) cells, which is mediated by abnormal hypermethylation in an AhR independent way and transcriptional regulation in an AhR dependent way. Furthermore, RNF182 exhibits low expression and hypermethylation in tumor tissues. RNF182 also significantly suppresses cell proliferation and induces cell cycle arrest in NSCLC cell lines.ConclusionThese results demonstrated that Bap inhibits RNF182 expression to promote lung cancer tumorigenesis through activating AhR and promoting abnormal methylation

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta-Analysis

Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38–3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03–1.07, p<0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors

Treatment of breast cancer cells with DNA demethylating agents leads to a release of Pol II stalling at genes with DNA-hypermethylated regions upstream of TSS

Inactivation of tumor suppressor genes plays an important role in tumorigenesis, and epigenetic modifications such as DNA methylation are frequently associated with transcriptional repression. Here, we show that gene silencing at selected genes with signs of DNA hypermethylation in breast cancer cells involves Pol II stalling. We studied several repressed genes with DNA hypermethylation within a region 1-kb upstream of the transcriptional start site that were upregulated after treatment with DNA demethylating agents, such as Azacytidine and several natural products. All those selected genes had stalled Pol II at their transcriptional start site and showed enhanced ser2 phosphorylated Pol II and elevated transcripts after drug treatment indicating successful elongation. In addition, a decrease of the epigenetic regulator LSH in a breast cancer cell line by siRNA treatment reduced DNA methylation and overcame Pol II stalling, whereas overexpression of LSH in a normal breast epithelial cell line increased DNA methylation and resulted in repression. Decrease of LSH was associated with reduced DNMT3b binding to promoter sequences, and depletion of DNMT3b by siRNA could release Pol II suggesting that DNMT3b is functionally involved. The release of paused Pol II was accompanied by a dynamic switch from repressive to active chromatin marks. Thus release of Pol II stalling can act as a mechanism for gene reactivation at specific target genes after DNA demethylating treatment in cancer cells

EBV-Encoded LMP1 Upregulates Igκ 3′Enhancer Activity and Igκ Expression in Nasopharyngeal Cancer Cells by Activating the Ets-1 through ERKs Signaling

Accumulating evidence indicates that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We previously found that the expression of the kappa light chain protein in NPC cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In the present study, we used NPC cell lines as models and found that LMP1-augmented kappa production corresponds with elevations in ERKs phosphorylation. PD98059 attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced kappa light chain gene expression. Luciferase reporter assays demonstrate that immunoglobulin κ 3′ enhancer (3′Eκ) is active in Igκ-expressing NPC cells and LMP1 upregulates the activity of 3′Eκ in NPC cells. Moreover, mutation analysis of the PU binding site in 3′Eκ and inhibition of the MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1-enhanced 3′Eκ activity is partly regulated by this site. PD98059 treatment also leads to a concentration-dependent inhibition of LMP1-induced Ets-1 expression and phosphorylation, which corresponds with a dose-dependent attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression. Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a decrease of Ig kappa light chain expression. Gel shift assays using nuclear extracts of NPC cells indicate that the transcription factor Ets-1 is recruited by LMP1 to the PU motif within 3′Eκ in vitro. ChIP assays further demonstrate Ets-1 binding to the PU motif of 3′Eκ in cells. These results suggest that LMP1 upregulates 3′Eκ activity and kappa gene expression by activating the Ets-1 transcription factor through the ERKs signaling pathway. Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3′ enhancer through activating transcription factors in non-B epithelial cancer cells

Posttranslational modifications of CXCR4: implications in cancer metastasis

CXCR4, the most widely expressed chemokine receptor in solid malignancies, has been implicated in cancer metastasis. However, how the activity of CXCR4 is regulated during carcinogenesis especially at the metastatic stage remains largely unknown. As with other G protein-coupled receptors, CXCR4 is subjected to posttranslational medications such as phosphorylation, ubiquitination, glycosylation, and sulfation. These posttranslational modifications contribute significantly to the heterogeneity of CXCR4 in terms of intracellular location, signaling, and functionality. We have shown that the difference in the sulfation level of CXCR4 is responsible for, if not all, the difference in the activities of CXCR4 between the highly metastatic and non-metastatic nasopharyngeal carcinoma (NPC) cell lines. Molecular mechanistic studies revealed that the Epstein-Barr virus-encoded oncoprotein LMP1 induces the expression of tyrosylprotein sulfotransferase 1 (TPST-1) through nuclear translocation of the epidermal growth factor receptor. This LMP1-regulated TPST-1 expression accounts for tyrosine sulfation of CXCR4 and is associated with the metastatic phenotype of NPC cell lines. Finally, in NPC patient specimens, there was a positive correlation between the expression of LMP1 and TPST-1 and the metastatic potential of NPC. Our findings provide the first evidence that the posttranslational modification of a chemokine receptor plays a role in cancer metastatic progression. Understanding the role of posttranslational modifications of chemokine receptors in cancer biology may provide new insights for developing attractive therapeutic targets in cancer therapy

Connecting Chromatin Modifying Factors to DNA Damage Response

Abstract: Cells are constantly damaged by factors that can induce DNA damage. Eukaryotic cells must rapidly load DNA repair proteins onto damaged chromatin during the DNA damage response (DDR). Chromatin-remodeling complexes use the energy from ATP hydrolysis to remodel nucleosomes and have well-established functions in transcription. Emerging lines of evidence indicate that chromatin-remodeling complexes are important and may remodel nucleosomes during DNA damage repair. New studies also reveal that ATP-dependent chromatin remodeling is involved in cell cycle progression, signal transduction pathways, and interaction and modification of DDR-related proteins that are specifically and intimately connected with the process of DNA damage. This article summarizes the recent advances in our understanding of the interplay between chromatin remodeling and DNA damage response