Nicotine exposure and transgenerational impact: a prospective study on small regulatory microRNAs

Early developmental stages are highly sensitive to stress and it has been reported that pre-conditioning with tobacco smoking during adolescence predisposes those youngsters to become smokers as adults. However, the molecular mechanisms of nicotine-induced transgenerational consequences are unknown. In this study, we genome-widely investigated the impact of nicotine exposure on small regulatory microRNAs (miRNAs) and its implication on health disorders at a transgenerational aspect. Our results demonstrate that nicotine exposure, even at the low dose, affected the global expression profiles of miRNAs not only in the treated worms (F0 parent generation) but also in two subsequent generations (F1 and F2, children and grandchildren). Some miRNAs were commonly affected by nicotine across two or more generations while others were specific to one. The general miRNA patterns followed a “two-hit� model as a function of nicotine exposure and abstinence. Target prediction and pathway enrichment analyses showed daf-4, daf-1, fos-1, cmk-1, and unc-30 to be potential effectors of nicotine addiction. These genes are involved in physiological states and phenotypes that paralleled previously published nicotine induced behavior. Our study offered new insights and further awareness on the transgenerational effects of nicotine exposed during the vulnerable post-embryonic stages, and identified new biomarkers for nicotine addiction.ECU Open Access Publishing Support Fun

O14.6 Sexual transmission of flaviviruses – a living systematic review

Introduction Flaviviruses, such as Zika virus (ZIKV), are pri-marily transmitted by infected arthropods. Evidence indicatesthat some of these viruses can be transmitted between persons through sexual intercourse. Sexual transmission of ZIKV is of special interest because of the risk of congenital abnormalities such as microcephaly. Several health agencies have produced guidelines on the prevention of sexual transmission of ZIKV, but there are many uncertainties. A systematic approach to assessment of the risk and epidemic potential of sexual transmission of flaviviruses is therefore crucial. Methods We conducted a systematic review with questions derived from a conceptual framework of the key parameters that drive infection transmission. We searched multiple databases and websites for studies of any design and in any language. Because of the rapid increase in publications, we have developed the review as a living systematic review, allowing continual updating of the findings. Results By January 10th 2017, we identified 28 unique reported cases of likely sexual transmission of ZIKV in 9 countries; 20 male to female, three female to male, one male to male, four unknown. In the US, 1% (36/4,310) of reported travel-associated ZIKV cases likely resulted from sexual contact. ZIKV has been detected by PCR for up to 188 days in semen and 14 days in vaginal secretions. Two of three included modelling studies quantified the contribution of the sexual transmission route, two studies estimated the proportion of ZIKV cases due to sexual transmission: 0.03 (95% CI: 0.001 – 0.46) and 0.23 (0.01 – 0.47). One publication about possible sexual transmission of West Nile virus has been identified so far. Conclusion Sexual transmission of ZIKV can occur but is likely not sufficient to sustain an epidemic. In high risk groups with frequent sexual partner change, it might contribute more to secondary transmission. We are tracking this fastmoving research field in a living systematic review to fill gaps in the evidence about the risks and prevention of sexual transmission of flaviviruses

Thermodynamic Driving Force of Hydrogen on Rumen Microbial Metabolism: A Theoretical Investigation

Hydrogen is a key product of rumen fermentation and has been suggested to thermodynamically control the production of the various volatile fatty acids (VFA). Previous studies, however, have not accounted for the fact that only thermodynamic near-equilibrium conditions control the magnitude of reaction rate. Furthermore, the role of NAD, which is affected by hydrogen partial pressure (PH 2), has often not been considered. The aim of this study was to quantify the control of PH 2 on reaction rates of specific fermentation pathways, methanogenesis and NADH oxidation in rumen microbes. The control of PH 2 was quantified using the thermodynamic potential factor (FT), which is a dimensionless factor that corrects a predicted kinetic reaction rate for the thermodynamic control exerted. Unity FT was calculated for all glucose fermentation pathways considered, indicating no inhibition of PH 2 on the production of a specific type of VFA (e.g., acetate, propionate and butyrate) in the rumen. For NADH oxidation without ferredoxin oxidation, increasing PH 2 within the rumen physiological range decreased FT from unity to zero for different NAD+ to NADH ratios and pH of 6.2 and 7.0, which indicates thermodynamic control of PH 2. For NADH oxidation with ferredoxin oxidation, increasing PH 2 within the rumen physiological range decreased FT from unity at pH of 7.0 only. For the acetate to propionate conversion, FT increased from 0.65 to unity with increasing PH 2, which indicates thermodynamic control. For propionate to acetate and butyrate to acetate conversions, FT decreased to zero below the rumen range of PH 2, indicating full thermodynamic suppression. For methanogenesis by archaea without cytochromes, FT differed from unity only below the rumen range of PH 2, indicating no thermodynamic control. This theoretical investigation shows that thermodynamic control of PH 2 on individual VFA produced and associated yield of hydrogen and methane cannot be explained without considering NADH oxidation.</p