Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action

The effects of norcantharidin (NCTD) on the growth of highly-metastatic human breast cancer cells were investigated by in vitro and ex vivo assays. Our results indicated that norcantharidin inhibited the in vitro growth of human breast cancer MDA-MB-231 cell line in dose- and time-dependent manners after the cancer cells were treated with norcantharidin at the concentrations of 6, 30 and 60 μmol/L for 24, 48 and 72 h. Moreover, the sera from the NCTD-treated rabbits after intravenous injection of NCTD at 15 and 30 min significantly suppressed the growth of the cancer cells ex vivo. The analyses by Hoechst 33258 staining and flow cytometry showed that the typical apoptotic morphological changes appeared and cell cycles arrested at G2/M phase in MDA-MB-231 cells after the cells were treated for 48 h with NCTD. In addition, NCTD down-regulated the expressions of anti-apoptotic protein Bcl-2 and up-regulated the expressions of pro-apoptotic protein Bax, eventually leading to the reduction of Bcl-2/Bax ratio in MDA-MB-231 cells. Furthermore, NCTD at concentrations of 6, 30 and 60 μmol/L dose-dependently reduced the phosphorylation of Akt and NF-κB expression in the breast cancer cell line. Induction of apoptosis and cell cycle arrest as well as reduction of Bcl-2/Bax ratio by NCTD may be the important mechanisms of action of NCTD suppressing the growth of MDA-MB-231 cells, which are associated with inhibition of the Akt and NF-κB signaling. Our findings suggest that norcantharidin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria

Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-D-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-D-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-D-aspartate receptor signalling in the pathogenesis of polymicrogyria

AKOVIA: Automated knowledge visualization and assessment

This emerging technology report reviews automated knowledge visualization and assessment (AKOVIA) which is a web-based tool for the analysis of natural language and graphical knowledge representations. The open architecture of AKOVIA enables a large variety of research and practical applications. It integrates a unique language-oriented methodology based on heuristics and generates seven quantitative similarity measures on the fly. AKOVIA has been successfully tested for reliability and validity. Given the limited availability of reliable and valid automated assessment methodologies, AKOVIA has the potential to be integrated into web-based applications and thus opening up numerous research as well as practical applications

Do candidates' ethnic background and gender matter? : an experimental approach

This chapter deals with the little analyzed (in the European context) impact of MPs’ ethnic and gender characteristics on voter choice by drawing on survey experiment data. The analysis shows mixed results. Although candidate gender does not seem to have any impact on the likelihood of supporting parliamentary candidates, having specific ethnic backgrounds can be an electoral burden. However, as with previous studies, the effect depends on voters’ ideological positions. The analysis also shows that, regardless of a candidate’s socio-demographic characteristics, it is party affiliation that matters most for voter choice in both countries. These are noteworthy results particularly for the case of France with its well-known candidate-centered electoral system

Do Candidates’ Ethnic Background and Gender Matter?:An Experimental Approach

This chapter deals with the little analyzed (in the European context) impact of MPs’ ethnic and gender characteristics on voter choice by drawing on survey experiment data. The analysis shows mixed results. Although candidate gender does not seem to have any impact on the likelihood of supporting parliamentary candidates, having specific ethnic backgrounds can be an electoral burden. However, as with previous studies, the effect depends on voters’ ideological positions. The analysis also shows that, regardless of a candidate’s socio-demographic characteristics, it is party affiliation that matters most for voter choice in both countries. These are noteworthy results particularly for the case of France with its well-known candidate-centered electoral system