Effectors are essential virulence proteins produced by a broad range of parasites, including viruses, bacteria, fungi, oomycetes, protozoa, insects and nematodes. Upon entry into host cells, pathogen effectors manipulate specific physiological processes or signaling pathways to subvert host immunity. Most effectors, especially those of eukaryotic pathogens, remain functionally uncharacterized. Here, we show that two effectors from the oomycete plant pathogen Phytophthora sojae suppress RNA silencing in plants by inhibiting the biogenesis of small RNAs. Ectopic expression of these Phytophthora suppressors of RNA silencing enhances plant susceptibility to both a virus and Phytophthora, showing that some eukaryotic pathogens have evolved virulence proteins that target host RNA silencing processes to promote infection. These findings identify RNA silencing suppression as a common strategy used by pathogens across kingdoms to cause disease and are consistent with RNA silencing having key roles in host defense.

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Thirdhand smoke (THS) is the accumulation of secondhand smoke on environmental surfaces. THS is found on the clothing and hair of smokers as well as on surfaces in homes and cars of smokers. Exposure occurs by ingestion, inhalation and dermal absorption. Children living in homes of smokers are at highest risk because they crawl on the floor, touch parents’ clothing/hair and household objects. Using mice exposed to THS under conditions that mimic exposure of humans, we show that THS increases cellular oxidative stress by increasing superoxide dismutase (SOD) activity and hydrogen peroxide (H2O2) levels while reducing the activity of antioxidant enzymes catalase and glutathione peroxidase (GPx) that break down H2O2 into H2O and O2. This results in lipid peroxidation, protein nitrosylation and DNA damage. Consequences of these cell and molecular changes are hyperglycemia and insulinemia. Indeed, we found reduced levels of insulin receptor, PI3K, AKT, all important molecules in insulin signaling and glucose uptake by cells. To determine whether these effects on THS-induced insulin resistance are due to increase in oxidative stress, we treated mice exposed to THS with the antioxidants N-acetyl cysteine (NAC) and alpha-tocopherol (alpha-toc) and showed that the oxidative stress, the molecular damage, and the insulin resistance, were significantly reversed. Conversely, feeding the mice with chow that mimics “western diet”, which is known to increase oxidative stress, while exposing the mice to THS, further increased the oxidative stress and aggravated hyperglycemia and insulinemia. In conclusion, THS exposure results in insulin resistance in the form of non-obese type II diabetes (NODII) through oxidative stress. If confirmed in humans, these studies could have a major impact on how people view exposure to environmental tobacco toxins, in particular to children, elderly and workers in environments where tobacco smoke has taken place.

Background: Third hand smoke (THS) forms when second hand smoke (SHS) tobacco toxins accumulate on surfaces such as walls, carpets and clothing and can result in adverse health effects. Objective: This study was designed to investigate the mechanism of THS-induced hepatic steatosis. Methodology: We used an in vivo exposure system that mimics exposure of humans to THS to investigate the effects of THS on hepatic lipid metabolism. THS-exposed mice were treated either with the liver-damaging drug, Nacetyl-p-aminophenol (APAP/Tylenol) to increase oxidative stress or with the antioxidants N-acetyl-cysteine and α-Tocopherol which decrease oxidative stress. Results: THS-exposed mice have higher levels of superoxide dismutase activity and H 2 O 2 levels. However, no significant changes in activity of the antioxidant enzymes catalase and glutathione peroxidase were found, implying the presence of high levels of hydrogen peroxide in the liver. Furthermore, THS-exposed mice also have a lower NADP+/NADPH ratio, indicating decreased ability of these mice to combat oxidative stress. THS-exposed mice show a decrease in ATP production, increase in aspartate aminotransferase (AST) activity, as well as increased molecular damage (lipid peroxidation, protein nitrosylation and DNA damage). Treating THS-exposed mice with APAP/Tylenol enhances the THS-induced damage whereas treating with antioxidants reduces the damage. THSexposed mice also have lower sirtuin 1 (SIRT1) levels compared to controls which decreased activation of 5' AMPactivated protein kinase (AMPK) and increased sterol regulatory element binding protein 1c (SREBP1c). Conclusion: THS-exposed mice on a normal diet have increased oxidative stress and damage mediated by oxidative stress, which results in alterations to the SIRT1/AMPK/SREPB1c signaling pathway. Increasing oxidative stress results in enhanced THS-induced damage whereas decreasing oxidative stress causes improvement in the THS-induced liver damage. Our results show that THS is a new risk factor contributing to the development of liver steatosis and highlight the danger of THS in general.

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