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Disruption of the enzymatic activities of the transcription factor TFIIH by the small molecules Triptolide (TPL) or THZ1 could be used against cancer. Here, we used the MCF10A-ErSrc oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had a synergic effect. TPL affects the interaction between XPB and p52, causing a reduction in the levels of XPB, p52 and p8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis, suggesting that transformed cells might rapidly develop resistance to TPL/THZ inhibitors. Some of these genes were also overexpressed in response to THZ1, of which depletion enhances the toxicity of TPL, and are possible new targets against cancer.

Thomas Countryman was a member of the US Foreign Service for 35 years, retiring in January 2017. He took office as assistant secretary of state for international security and nonproliferation in Se...

With reference to the collection of the Irkutsk Regional Museum, the article outlines the history of Arita porcelain, one of the leading ceramic centers in Japan. The author enumerates the founders of the technique, also illustrating sustained progress in ceramic production, which became a competitor of Chinese porcelain in Europe. The author discusses how Japanese potters succeeded in producing valuable porcelain products which were bought, in addition to Dutch merchants, by Chinese traders. Special attention is paid to the Meiji period, a time of transition that saw the formation of modern Japanese culture. During this period there was a modernization of traditional modes of production, but the identity of national culture was kept intact, which was reflected in the porcelain decoration designs. The author characterizes artistic styles of decoration (Kakiemon, Iro-Nabeshima, and Nisikide Imari) that received worldwide fame. Masters that created them became a national treasure of the Japanese people as they both preserved the generations-long techniques and demonstrated a profound knowledge of production cycles of individual ceramic enterprises. The article analyses porcelain from the museum collection as a source that altered the Europeans’ view upon arts and crafts of Japan that had been perceived as underdeveloped previously. The article contains data on the brands and authors’ inscriptions on the porcelain ware of the period. В статье, основанной на вещественном материале музейной коллекции, приводится история возникновения фарфора Арита, одного из ведущих керамических центров Японии. Называются основоположники японского фарфора. Показан поступательный ход керамической продукции, ставшей конкурентоспособной китайской. Рассказывается о том, как японским гончарам удалось наладить выпуск ценной фарфоровой продукции, которую, кроме голландских купцов, скупали и китайские торговцы фарфором. Особое значение придается периоду Мэйдзи, его обновленческим преобразованиям, когда закладывалась современная культура японского народа. Создаваемая модернизация традиционных форм производства, позволила сохранить самобытность национальной культуры, в том числе отразившуюся в декоре росписи фарфора. Характеризуются художественные стили росписи: какиэмон, иро-набэсима, имари-нисикидэ, получившие всемирную известность. Мастера, создавшие их, стали национальным достоянием японского народа: им была свойственна не только преемственная связь между поколениями гончаров, но и глубокое знание традиционно отлаженных производственных циклов, принятых на конкретных керамических предприятиях. Анализируется коллекционный фарфор, как основной источник исследования, перевернувший представления европейцев о художественных промыслах Японии, ранее считавшихся неразвитыми. Проводится атрибуция изделий по маркам и авторским надписям.

The estrogen receptors (ERα and ERβ) which are ligand inducible nuclear receptors are recognized as pharmaceutical targets for diseases such as osteoporosis and breast cancer. There is an increasing interest in the discovery of subtype Selective Estrogen Receptor Modulators (SERMs). A series of novel β-lactam compounds with estrogen receptor modulator properties have been synthesized. The antiproliferative effects of these compounds on human MCF-7 breast tumor cells are reported, together with binding affinity for the ERα and ERβ receptors. The most potent compound 15g demonstrated antiproliferative effects on MCF-7 breast tumor cells (IC50 = 186 nM) and ERα binding (IC50 = 4.3 nM) with 75-fold ERα/β receptor binding selectivity. The effect of positioning of the characteristic amine containing substituted aryl ring (on C-4 or N-1 of the β-lactam scaffold) on the antiproliferative activity and ER-binding properties of the β-lactam compounds is rationalized in a molecular modeling study.