RNA interference-mediated knockdown of p21WAF1 enhances anti-tumor cell activity of oncolytic adenoviruses

The ability of oncolytic adenoviruses to replicate in and lyse cancer cells offers a potential therapeutic approach. However, selectivity and efficacy of adenovirus replication need to be improved. In this study, we present that loss of p21WAF1 promotes adenovirus replication and more effective cell killing. To test our hypothesis, we took HCT116 colon cancer cell lines carrying deletions of either p21WAF1 or p53, and infected these cell lines with wild-type adenovirus (WtD) or the oncolytic adenoviruses, ONYX-015 and Delta-24. We found that WtD, ONYX-015 and Delta-24 induced stronger cytopathic effects in HCT116 p21−/− cells compared with HCT116-WT cells. This was accompanied by increased virus production. siRNA-mediated knockdown of p21WAF1, and similarly of p27KIP1, in HCT116-WT cells also enhanced replication of and cell killing by these viruses. Furthermore, we found that TE7, an esophageal carcinoma cell line, also showed a strong cell-killing effect and virus production when p21WAF1 expression was suppressed by RNA interference before adenoviruses infection. Also, H1299 and DU-145 cells transfected with p21WAF1 siRNA showed higher virus production after ONYX-015 and Delta-24 infections. These observations suggest that p21WAF1 plays a role in mediating replication of oncolytic viruses with potential implications for adenoviral therapy of cancer

Effect of Parathion-Methyl on Amazonian Fish and Freshwater Invertebrates: A Comparison of Sensitivity with Temperate Data

Parathion-methyl is an organophosphorous insecticide that is widely used in agricultural production sites in the Amazon. The use of this pesticide might pose a potential risk for the biodiversity and abundance of fish and invertebrate species inhabiting aquatic ecosystems adjacent to the agricultural fields. Due to a lack of toxicity data for Amazonian species, safe environmental concentrations used to predict the ecological risks of parathion-methyl in the Amazon are based on tests performed with temperate species, although it is unknown whether the sensitivity of temperate species is representative for those of Amazonian endemic species. To address this issue, the acute toxic effect (LC50–96 h) of parathion-methyl was assessed on seven fish and five freshwater invertebrate species endemic to the Amazon. These data were used to compare their pesticide sensitivity with toxicity data for temperate species collected from the literature. The interspecies sensitivity was compared using the Species Sensitivity Distribution (SSD) concept. The results of this study suggest that Amazonian species are no more, or less, sensitive to parathion-methyl than their temperate counterparts, with LC50 values ranging from 2900 to 7270 μg/L for fish and from 0.3 to 319 μg/L for freshwater arthropods. Consequently, this evaluation supports the initial use of toxicity data of temperate fish and freshwater invertebrate species for assessing the effects of parathion-methyl on Amazonian freshwater ecosystems

Diversity and Impacts of Mining on the Non-Volant Small Mammal Communities of Two Vegetation Types in the Brazilian Amazon

The CarajaÂs National Forest contains some of the largest iron ore deposits in the world. The majority of the minerals are found below a plant community known as Savana Metalo fila, or ªCangaº, which represents only 3% of the landscape within the CarajaÂs National Forest (CNF). The aim of our study was to understand the diversity of community of non-volant small mammals in the two predominant vegetation types: Ombrophilous Forest and Canga, and to examine how mining impacts these communities. Sampling was conducted from January 2010 to August 2011 in 11 sampling sites divided by the total area of Canga and 12 sampling sites in the forest, totalizing 23 sites. Of these, 12 sites (Canga and Forest) were considered impacted areas located close to the mine (\u3c\u3c 900 meters) and 11 sites (Canga and Forest), serving as controls, which were at least 7,000 meters from the mine. We recorded 28 species, 11 from the Order Didelphimorphia and 17 from the Order Rodentia. The two forest types shared 68.42% of the species found in the CNF. A gradient analysis (Non-metric multidimensional scaling) revealed that the first axis clearly separated the nonflying small mammal communities by vegetation type. Occupancy models showed that the detectability of species was affected by the distance from the mining activities. Of all the small mammals analyzed, 10 species were positively affected by the distance from mining in areas impacted (e.g. more likely to be detected farther from mining areas) and detectability was lower in impacted areas. However, three species were negatively affected by the distance from mining, with higher detectability in the impacted areas, and seven species showed no effect of their proximity to mining operations. To date, there are no studies in Brazil about the impact of mining on mammals or other vertebrates. This study reveals that the effect of mining may go beyond the forest destruction caused by the opening of the mining pits, but also may negatively affect sensitive wildlife species. Supplemental File 01 is attached below, in pdf and original docx file formats