Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells

Nutrient use and nutrient use efficiency of crops in a high CO2 atmosphere

Tausz, M ORCiD: 0000-0001-8205-8561Abstract Atmospheric CO2 concentrations [CO2] are continually increasing and are predicted to reach ~550 μmol mol-1 by 2050, about a 40 % increase from 2013 levels. Such a large increase in one of the key resources for plant growth will have significant effects on all plants, as carbon assimilation and, consequently, growth and yield is stimulated by the so-called ‘CO2 fertilisation effect’. The one sided increase in carbohydrate acquisition leads to changes in the chemical composition of plants: despite decreases in nutrient concentrations in plant tissues, the greater biomass developed by crops under elevated [CO2] could lead to increased nutrient demand. Nutrient use efficiency in terms of yield divided by available nutrient may improve, but grains or vegetative plant parts have decreased protein and mineral nutrient concentrations, which can diminish market and nutritious value. A number of hypotheses have been proposed to explain the decreases in nutrient concentra- tions, among them: (1) Dilution by increased biomass, (2) decreased mass flow, (3) changes in root architecture and function, (4) decreased nitrate eduction, and (5) changes in nutrient allocation and remobilisation. In addition, elevated [CO2] is likely to change soil processes, including nutrient supply. The extent to which some or all of these contribute to changes in crop nutrition and yield quality is currently unknown because most have not been sufficiently tested under relevant field conditions. This chapter gives an overview of the changes in plant nutrition and trade-offs under elevated [CO2] to point out that current and future efforts towards improved plant nutrient efficiency should explicitly take into consideration rising [CO2]. In particular, field testing of putative nutrient use efficiency traits and nutrient management strategies should include elevated [CO2] as a relevant factor in suitable exposure systems such as Free Air CO2 Enrichment (FACE) technology