Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect

The histone deacetylase inhibitors (HDACi) have demonstrated anticancer efficacy across a range of malignancies, most impressively in the hematological cancers. It is uncertain whether this clinical efficacy is attributable predominantly to their ability to induce apoptosis and differentiation in the cancer cell, or to their ability to prime the cell to other pro-death stimuli such as those from the immune system. HDACi-induced apoptosis occurs through altered expression of genes encoding proteins in both intrinsic and extrinsic apoptotic pathways; through effects on the proteasome/aggresome systems; through the production of reactive oxygen species, possibly by directly inducing DNA damage; and through alterations in the tumor microenvironment. In addition HDACi increase the immunogenicity of tumor cells and modulate cytokine signaling and potentially T-cell polarization in ways that may contribute the anti-cancer effect in vivo. Here, we provide an overview of current thinking on the mechanisms of HDACi activity, with attention given to the hematological malignancies as well as scientific observations arising from the clinical trials. We also focus on the immune effects of these agents

Further development of small hydropower facilities will significantly reduce sediment transport to the Pantanal wetland of Brazil.

Small hydropower (SHP) facilities, which are defined by installed capacities 20% net retention of suspended sediments, two others retained between 10 and 20%, seven were within 10%, and six showed >10% net release. Bedload sediment transport was a small component of total sediment transport in rivers with high total sediment loads. Multiyear series of satellite images confirm sediment accumulation in several cases. Model predictions of the impacts of future hydropower facilities on suspended sediment concentrations and transport show retention of a large fraction (often much >20%) of sediment inputs. Summing riverine transport rates for inflows into the Pantanal indicates that currently envisioned future hydropower development would reduce the suspended sediment transport by 62% from the current rate. This study shows that if SHPs are built on sediment-rich rivers, this may prove problematic for the facilities as well as for downstream ecosystems. These results support recommendations that several river systems presently lacking dams in their lower reaches should be excluded from future hydropower development to maintain the sediment supply to the Pantanal