A distinct feature of the Toll-like receptor 4 (TLR4) is its ability to trigger both MyD88-dependent and MyD88-independent signalling, culminating in activation of pro-inflammatory NF-κB and/or the antiviral IRF3. Although TLR4 agonists (lipopolysaccharides; LPSs) derived from different bacterial species have different endotoxic activity, the impact of LPS chemotype on the downstream signalling is not fully understood. Notably, different TLR4 agonists exhibit antitumoural activity in animal models of glioma, but the underlying molecular mechanisms are largely unknown. Thus, we investigated the impact of LPS chemotype on the signalling events in the human glioma cell line U251. We found that LPS of Escherichia coli origin (LPSEC) leads to NF-κBbiased downstream signalling compared to Salmonella minnesota-derived LPS (LPSSM).Exposure of U251 cells to LPSEC resulted in faster nuclear translocation of the NF-κB subunit p65, higher NF-κB-activity and expression of its targets genes, and higher amount of secreted IL-6 compared to LPSSM. Using super-resolution microscopy we showed that the biased agonism of TLR4 in glioma cells is neither a result of differential regulation of receptor density nor of formation of higher order oligomers. Consistent with previous reports, LPSEC-mediated NF-κB activation led to significantly increased U251 proliferation, whereas LPSSM-induced IRF3 activity negatively influenced their invasiveness. Finally, treatment with methyl-βcyclodextrin (MCD) selectively increased LPSSM-induced nuclear translocation of p65 and NF-κB activity without affecting IRF3.Our data may explain how TLR4 agonists differently affect glioma cell proliferation and migration.

No abstract

Epikura, na poły apologetycznym, na poły polemicznym wobec twórcy Ogrodu studium krytycznym, tylko raz wspomina o sztuce i epikurejskiej nad nią refleksji. Stwierdza mianowicie: Celem filozofii-mówi on [Epikur]-jest umiejętność zapewnienia człowiekowi szczęścia. Wszystkie więc nauki (teoretyczne) niedążące do tego celu, lecz wiodące tylko do poznania-jak np. dialektyka, matematyka, filologia-nie mają wartości. Muzyka np. jest rzeczą przyjemną, ale teoria muzyki bezużyteczną. 3

No abstract

Aratus' Phaenomena describes the constellations as a sign system devised by Zeus for the benefit of human beings. This article argues that Aratus figuratively depicts these signs as though they were "letters in the sky," a veritable text inscribed in nature. Through a cumulative argument that considers, among other things, the hermeneutics of Aratean sign-reading, the myth of Dike, Aratus' acrostic and other forms of letter play, and the reception of the Phaenomena , the article arrives at the conclusion that the writing metaphor is indeed pervasive in Aratus' poem. The Phaenomena thus presents an important early instance of a pervasive trope in the history of ideas, the concept of the "readability" of the world.