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Simple Summary: Natural products derived from plants have numerous clinical applications, including anti-cancer activity. In the present study, we identified three different plant extracts as strong inducers of cell death that were not reported previously. We focused on the most potent of these plants, Vernonanthura nudiflora (Vern). We demonstrated that the plant extracts obtained by treatment with a water and ethanol mixture killed tumor cells via multiple routes. These include impairing cell energy and metabolism, generating reactive oxygen species, increasing intracellular Ca2+, and inducing mitochondria-mediated apoptosis. We connected these activities to increased levels of the mitochondrial gatekeeper protein, VDAC1, which is associated with metabolism and apoptosis regulation. In a glioblastoma mouse model, Vern extract strongly inhibited tumor growth and induced massive tumor cell death, including cancer stem cells, by inhibiting blood supply and modulating the tumor microenvironment. The multipronged effects of hydroethanolic Vern extract make it a promising candidate for treating cancer. The mitochondrial voltage-dependent anion channel 1 (VDAC1) protein is involved in several essential cancer hallmarks, including energy and metabolism reprogramming and apoptotic cell death evasion. In this study, we demonstrated the ability of hydroethanolic extracts from three different plants, Vernonanthura nudiflora (Vern), Baccharis trimera (Bac), and Plantago major (Pla), to induce cell death. We focused on the most active Vern extract. We demonstrated that it activates multiple pathways that lead to impaired cell energy and metabolism homeostasis, elevated ROS production, increased intracellular Ca2+, and mitochondria-mediated apoptosis. The massive cell death generated by this plant extract's active compounds involves the induction of VDAC1 overexpression and oligomerization and, thereby, apoptosis. Gas chromatography of the hydroethanolic plant extract identified dozens of compounds, including phytol and ethyl linoleate, with the former producing similar effects as the Vern hydroethanolic extract but at 10-fold higher concentrations than those found in the extract. In a xenograft glioblastoma mouse model, both the Vern extract and phytol strongly inhibited tumor growth and cell proliferation and induced massive tumor cell death, including of cancer stem cells, inhibiting angiogenesis and modulating the tumor microenvironment. Taken together, the multiple effects of Vern extract make it a promising potential cancer therapeutic. [ABSTRACT FROM AUTHOR]

The article estimates seat distribution among political parties in Slovakia's Parliament using the most recent electoral outcomes and varying a constituency magnitude and a seat distribution formula. The goal of the article is to discuss introducing possible minor reforms of the electoral system with the aim to eliminate party system fragmentation and to reinforce governing efficiency. Consideration is given to the historical evolution of the electoral system and past amendment proposals. Results demonstrate that minor electoral reform would not by itself lead to the desired changes in the party system. In an endeavour to reduce the number of political parties in the Parliament, a change of at least two aspects of the electoral systems would be necessary - seat distribution formula and constituency magnitude. [ABSTRACT FROM AUTHOR]

The study uses the 2017 parliamentary elections results to analyses spatial patterns of votes in the city of Prague. A unique approach combining contextual and compositional data is introduced. Census data and data indicating the quality of life are reassigned to a shared entity -- an address point, and analysed via automatic linear modelling. The model explained 69 % of spatial variance of votes share for the conservative TOP 09 party and the winning ANO 2011 movement, but only 19 % for the Pirate Party and the Mayors and Independence movement. Future research might focus on finding variables which would explain spatial variance of these parties' vote shares. Abother possibility is the development of a methodology for studying votes spatiality within urban areas, in order to develop a robust theory. [ABSTRACT FROM AUTHOR]

Purpose: While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in nonmalignant and premalignant breast tissue. Here, we investigate and quantify NK cell marker CD56 and activating ligand MICA in breast tissue with benign breast disease.Methods: Serial tissue sections from 88 subjects, 44 with benign breast disease (BBD) who remained cancer-free, and 44 with BBD who later developed cancer, were stained with H&E, anti-MICA, and anti-CD56. Up to ten representative lobules were identified on each section. Using digital image analysis, MICA and CD56 densities were determined for each lobule, reported as percent of pixels in the lobule that registered as stained by each antibody. Analyses were performed on a per-subject and per-lobule basis.Results: Per-subject multivariate analyses showed associations of CD56 and MICA with age: CD56 was increased in older subjects (p = 0.03), while MICA was increased in younger subjects (p = 0.005). Per-lobule analyses showed that CD56 and MICA levels were both decreased in lobules with fibrocystic change, with median levels of CD56 and MICA staining, respectively, at 0.31 and 7.0% in fibrocystic lobules compared to 0.76 and 12.2% in lobules without fibrocystic change (p < 0.001 for each). Among fibrocystic lobules, proliferative/atypical lobules showed significantly lower expression compared to nonproliferative lobules for MICA (p = 0.02) but not for CD56 (p = 0.80).Conclusion: Levels of CD56+ NK cells and activating ligand MICA were decreased in breast lobules with fibrocystic change, and MICA levels showed a significant stepwise decrease with increasing histopathologic abnormality. MICA levels were also significantly decreased in older subjects, who generally have higher risk of developing cancer. These findings advance a model in which MICA promotes cytotoxic activity in CD56+ NK cells to protect against tumorigenesis in breast lobules, and suggest further research is warranted. [ABSTRACT FROM AUTHOR]

The goal of the article is to describe spatial patterns of the 2016 general election voting support on the administrative territory of the city of Kosice. The analysis contains parties that exceeded 0.05 threshold at the national level. The description identifies each party's territory of voting support, territory of stable voting support (2010 - 2016), and spatial variance. The explanation is based on compositional approach using the Lipset-Rokkan model. The only core-periphery cleavage is markedly present in voting behaviour of Kosice inhabitants. The analysis also shows distinctions in voting support among different parts of the city. [ABSTRACT FROM AUTHOR]