Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance.

Oncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear. Here we use Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. These findings suggest that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients.

Supramolecular networks of 10-(2-hydroxyethyl)acridin-9(10H)-one and 10-(2-chloroethyl)acridin-9(10H)-one.

Both 10-(2-hydroxyethyl)acridin-9(10H)-one, C15H13NO2, and 10-(2-chloroethyl)acridin-9(10H)-one, C15H12ClNO, have monoclinic (P21/c) symmetry and supramolecular three-dimensional networks. But the differences in the intermolecular interactions displayed by the hydroxy group and the chlorine substituent lead to stronger intermolecular π-stacking interactions and hydrogen bonding, and hence a significantly higher melting point for the former.

Synthesis and supramolecular networks of 5,6-dioxo-1,10-phenanthroline-2,9-dicarboxylic acid dihydrate and its first coordination compound cis-diaquachlorido(5,6-dioxo-1,10-phenanthroline-2,9-dicarboxylic acid-κ4O2,N,N',O9)manganese(II) chloride dihydrate.

5,6-Dioxo-1,10-phenanthroline-2,9-dicarboxylic acid dihydrate (H(2)pdda·2H(2)O), C(14)H(6)N(2)O(6)·2H(2)O, was obtained by carbonylation of 1,10-phenanthroline-2,9-dicarboxylic acid. Its first coordination compound, [MnCl(C(14)H(6)N(2)O(6))(H(2)O)(2)]Cl·2H(2)O, in which the H(2)pdda ligand remains protonated, was synthesized in aqueous acetic acid. H(2)pdda chelates one water molecule via hydrogen bonds in H(2)pdda·2H(2)O, whereas in the coordination compound it chelates one heptacoordinate Mn(II) atom via coordination bonds. The N atoms in H(2)pdda·2H(2)O and the Cl atoms in the coordination compound are also involved in hydrogen bonds. Extensive hydrogen bonding results in supramolecular networks in both compounds.

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations.

BACKGROUND: The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000-30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario. RESULTS: In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations. CONCLUSION: We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.