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The 2019 European Parliament (EP) elections produced remarkable gains for Green parties throughout the European Union (EU). We analyse in how far different national electoral contexts can explain the electoral success of Green parties in EU member states. On the theoretical side, we argue that an increased salience of EU environmental politics has led to 'green issue voting'. However, the relevance of environmental issue preferences depends on the electoral context in which Green parties compete for votes. Specifically, we expect 'green issue voting' to be most relevant for the smaller Green parties who own the environmental issue. On the empirical side, we test our argument by combining survey data collected by the European Election Study with information on party positions provided by the Comparative Manifestos Project. Our findings strongly suggest that the relevance of 'green issue voting' in the 2019 EP elections was conditionally dependent on the national electoral context. [ABSTRACT FROM AUTHOR]

This article analyses the organisational development of political parties in new democracies. In particular, focusing on Korean cases, it extends the existing discussions over party organisation into Asian democracies by examining the ways of overcoming the traditions of clientelism. Employing a dimensional approach, the evaluation relies on three core characteristics of party organisation by utilising a novel source of the official data of party organisation in Korea and a data of the Comparative Manifesto Project. Covering the long-term variations on organisational development, 1992–2018, it finds that Korean parties have experienced the waning power of the Party Central Office and the weakening ties with civil society. Despite these characteristics of development of a cartel-party type organisation, analysis does not confirm the expected of convergence of programmatic appeals between parties. These mixed findings lead to the conclusion that Korean parties have developed toward not a catch-all organisation, but a loosely cartelised organisation. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the major causes of therapeutic failure in breast cancer patients. In this study, the mechanism of chemoresistance in human triple-negative breast cancer (TNBC) cells (MDA-MB-231) induced by doxorubicin (DOX) gradient was investigated. These DOX-resistant cells showed higher drug efflux rate, increased anchorage-independent growth when cultured in suspension, and increased tumor-forming ability in nude mice, compared to the wild-type MDA-MB-231 cells. RNA sequencing analysis showed an increase in the expression of genes involved in membrane transport, antiapoptosis, and histone regulation. Kaplan-Meier plot analysis of TNBC patients who underwent preoperative chemotherapy showed that the relapse free survival (RFS) of patients with high HIST1H2BK (histone cluster 1 H2B family member k) expression was significantly lower than that of patients with low HIST1H2BK expression. Quantitative real-time PCR confirmed that the level of HIST1H2BK expression was increased in resistant cells. The cytotoxicity analysis showed that the DOX resistance of resistant cells was reduced by treatment with a histone deacetylase (HDAC) inhibitor. Our results suggest that, in DOX-resistant cells, HIST1H2BK expression can be rapidly induced by the high expression of genes involved in membrane transport, antiapoptosis, and histone regulation. In conclusion, chemoresistance in MDA-MB-231 cells can occur in a relatively short period by DOX gradient via this previously known mechanism of resistance, and DOX resistance is dependent on the specificity of resistant cells to HDAC. [ABSTRACT FROM AUTHOR]

Aberrant interleukin-1 beta (IL-1β) expression is associated with cancer development, metastasis, and poor prognosis. Here, we have investigated the regulatory mechanism of IL-1β expression, and the inhibitory effect of zerumbone (ZER) on IL-1β expression and IL-1β-induced signatures, including cell invasion and signaling activation in triple negative breast cancer (TNBC) cells. The basal IL-1β and cell invasiveness levels were significantly higher in TNBC cells, compared with non-TNBC cells. The invasiveness of TNBC cells was also increased following IL-1β treatment. In contrast, the invasiveness of TNBC cells was decreased following IL-1 receptor antagonist (IL-1RA) treatment. Additionally, the basal IL-1β level and the invasiveness of TNBC cells were decreased by Bay11-7085. In contrast, overexpression of NF-κB (p65) caused an increase in IL-1β expression in TNBC cells. Our results showed that treatment with ZER decreased the basal IL-1β expression level, and the phosphorylation level of NF-κB, in TNBC cells. Furthermore, we found that ZER completely suppressed IL-1β-induced NF-κB phosphorylation, but did not suppress IL-1β-induced Akt phosphorylation, in TNBC cells. Our results also demonstrate that IL-1β-induced cell invasion is suppressed by ZER in TNBC cells. Taken together, we demonstrated that IL-1β expression is regulated by the NF-κB-dependent pathway, and that elevated IL-1β is directly influencing the invasiveness of TNBC cells. ZER down-regulates IL-1β expression through the inhibition of NF-κB activity, and then suppresses cell invasiveness of TNBC. [ABSTRACT FROM AUTHOR]

The system of single rapporteurships was introduced at times when the European Parliament was trying hard to establish its powers vis-à-vis the Council of Ministers. Over the years, party politics has become increasingly important for European Union legislation. This historical development triggers the question to what extent the powers of the rapporteur depend on her partisan ties to the Council of Ministers. In order to answer this question we analyse legislative reports authored between 2004 and 2009. We argue that the rapporteur can successfully form coalitions inside the European Parliament. However, if the rapporteur's party is represented inside the Council of Ministers, she may be suspected of supporting national rather than partisan interests. Therefore, representation in the Council is a double-edged sword: rapporteurs whose parties are in government find it easier to gain information on the proceedings inside the Council, but they lose credibility with their partisan peers inside the European Parliament. [ABSTRACT FROM AUTHOR]

Abstract: Although it has been suggested that smad7 blocks downstream signaling of TGF-β, the role of smad7 in the EGF signaling pathway has not been fully elucidated. We determined the effect of smad7 on EGF-induced MMP-9 expression in SKBR3 breast cancer cells. The expression of smad7 and MMP-9 was increased by EGF or TGF-β1, respectively, and further increased by EGF and TGF-β1 co-treatment. EGF induced the phosphorylation of EGFR, smad3, ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478. In addition, EGF-induced MMP-9 expression was inhibited by UO126 (a MEK1/2 inhibitor) or SIS3 (a smad3 inhibitor), but not by SP600125 (a JNK inhibitor). Interestingly, EGF-induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK. EGF- or TGF-β1-induced MMP-9 expression was completely decreased by adenoviral-smad7 (Ad-smad7) over-expression. We also investigated the role of smad3 on EGF-induced MMP-9 expression and showed that EGF-induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF-induced MMP-9 expression was further increased by smad3 over-expression, as expected. This study showed that EGF-induced smad3 phosphorylation mediates the induction of MMP-9, whereas smad7 inhibits TGF-β1 as well as the EGF signaling pathway in SKBR3 cells. [Copyright &y& Elsevier]

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by PFT-α in MDA-MB231 breast cancer cells with mutant p53. In addition, the expression level of COX-2 was also increased by PFT-α in normal fibroblasts as well as in HT1080 fibrosarcoma cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in response to PFT-α, we pretreated cells with a mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K) inhibitor (LY294002). PFT-α-induced COX-2 expression was significantly decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was increased by PFT-α, but not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI-3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr-Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection, but not by myr-Akt. Taken together, we have demonstrated that PFT-α-induced COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast cancer cells. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR) is one of the major alkaloids, and it has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9 expressions, which are predictors of metastasis and invasion in breast cancer cells. Methods: MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR. The levels of MMP-1 protein and PKC-α phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-α knock-down was examined by PKC-α siRNA transfection. Results: The basal levels of both the MMP-1 and MMP-9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In contrast, TPA, which is a tumor promoter, significantly increased the levels of the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1 and MMP-9 expressions were completely decreased by Go6983 and PKC-α siRNA, respectively. TPA-induced PKC-α phosphorylation was dose-dependently decreased by BBR treatment. Conclusion: The TPA-induced PKC-α phosphorylation is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by berberine. Therefore, we suggest that berberine may be used as a candidate drug for the inhibition of metastasis of human breast cancer. [Copyright &y& Elsevier]

Gut microbiota dysbiosis and intestinal epithelial cell barrier dysfunction are associated with diseases such as inflammatory bowel disease and type 2 diabetes. To study the interaction of gut microbes and intestinal epithelial cells, in vitro model systems for co-culturing intestinal cells and gut microbes are essential. Since most gut microorganisms are anaerobic bacteria, it is difficult to co-culture microbes with intestinal epithelial cells that require oxygen during culture. We have developed a novel gut microbialepithelial cell (GMEC) co-culture system, a microfluidic chip in an anaerobic chamber with oxygen gradient within the chip. Appropriate co-culture flow rates were determined based on the experimental observation as well as fluid dynamics and molecular transport simulations. Using GMEC system, Escherichia coli and Lactobacillus plantarum were co-cultured with gut epithelial cell line, Caco-2. We expect that our GMEC co-culture system can potentially be a useful platform for studying the interaction between intestinal epithelial cells and gut microbes. [ABSTRACT FROM AUTHOR]

This study proposes a novel approach for measuring political polarization using a user-activity-based model. By exploiting data from comments, user activity in this study is defined based on features such as coverage, duration, and enthusiasm. To determine these features, we collect information on the activities of users from South Korean YouTube channels. Notably, the collected data of the model contains approximately 11 M comments from more than 600 K users based on 37 K videos of 77 YouTube channels. To handle the big data collection, we deploy a web-based platform called TubePlunger to collect video information (e.g., comments, replies, etc.) automatically from YouTube channels. The output of the model reveals that the users are strongly polarized because the number of neutral users is very small (approximately 8% of the total). We then applied this model to the other channels in the testing dataset to define polarization with a bias percentage and to visualize the user activity distribution. The experimental results show that there are 30 fully polarized YouTube channels (16 left-wing channels and 14 right-wing channels) with a measured bias ratio higher than 70%. Our method of analyzing social network data based on user activity provides the foundation for polarization analysis that can be applied to fields other than politics. [ABSTRACT FROM AUTHOR]

Spheroids are recognized for replicating the physiological microenvironment of tumours. However, because of the lack of controllability of the spheroid size, the response to anticancer drugs is variable in conventional spheroid culture methods. In this paper, we describe a method to generate several hundreds of spheroids of various types of cancer cells including patient derived cancer cells (PDCs) using a microfluidic device with pillars (diameter: 40 μm, height: 70 μm, center-to-center distance: 140 μm), called a microfluidic pillar array (μFPA) device. About three hundred glioma (U87) spheroids were obtained in the μFPA device within 3 days, and about 90% of them ranged from 175 to 225 μm. These spheroids were more resistant to doxorubicin at 10 μM than U87 cells in a monolayer. The former showed higher expression of CD133, a cancer stem cell marker, than the latter. Hypoxia inducible factor-1α (HIF-1α), another cancer stem cell marker, was found in the nucleus of the former, but found in the cytoplasm of the cells in a monolayer. Drug responses of spheroids of another glioma cell line (U251) and triple negative breast cancer (TNBC) primary cells were also easily quantified by measuring changes in spheroid size at different concentrations of their respective drug on the μFPA device. The μFPA device can be a powerful platform for obtaining uniform spheroids and monitoring the drug response of cancer cells including PDCs. [ABSTRACT FROM AUTHOR]

Background/Aims: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. Methods: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. Results: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. Conclusion: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]