Rome in its setting. Post-glacial aggradation history of the Tiber River alluvial deposits and tectonic origin of the Tiber Island.

The Tiber valley is a prominent feature in the landscape of ancient Rome and an important element for understanding its urban development. However, little is known about the city's original setting. Our research provides new data on the Holocene sedimentary history and human-environment interactions in the Forum Boarium, the location of the earliest harbor of the city. Since the Last Glacial Maximum, when the fluvial valley was incised to a depth of tens of meters below the present sea level, 14C and ceramic ages coupled with paleomagnetic analysis show the occurrence of three distinct aggradational phases until the establishment of a relatively stable alluvial plain at 6-8 m a.s.l. during the late 3rd century BCE. Moreover, we report evidence of a sudden and anomalous increase in sedimentation rate around 2600 yr BP, leading to the deposition of a 4-6m thick package of alluvial deposits in approximately one century. We discuss this datum in the light of possible tectonic activity along a morpho-structural lineament, revealed by the digital elevation model of this area, crossing the Forum Boarium and aligned with the Tiber Island. We formulate the hypothesis that fault displacement along this structural lineament may be responsible for the sudden collapse of the investigated area, which provided new space for the observed unusually large accumulation of sediments. We also posit that, as a consequence of the diversion of the Tiber course and the loss in capacity of transport by the river, this faulting activity triggered the origin of the Tiber Island.

PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells.

This study investigated the involvement of PPARgamma and PPARalpha signaling in the synergistic anticancer activity of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) and docosahexaenoic acid (DHA) in human cancer cells. The synergistic cytotoxicity of DHA and clioquinol was demonstrated in nine human cancer cell lines representing different tissues of origin. A2780, a well-established ovarian cancer model system, was chosen for further characterization because of its sensitivity to DHA and clioquinol. Both PPARalpha and PPARgamma were expressed in A2780 cells when analyzed with western blotting and reporter gene technique. Treatment of the cells with clofibrate (a PPARalpha agonist) and clioquinol for three days mimicked the synergy of DHA and clioquinol, whereas this synergy could not be seen with the use of troglitazone (a PPARgamma agonist) and clioquinol, suggesting that PPARalpha signaling is involved in the synergistic action. When used alone, the IC50 of clofibrate was 513 microM in A2780 cells. However, the addition of 5 microM clioquinol to clofibrate-treated cells led to a dramatic reduction of its IC50 value (148 microM). The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells.