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The plant hormone abscisic acid (ABA) induces a developmental switch in the aquatic fern Marsilea quadrifolia, causing the formation of aerial type characteristics, including the elongation of petioles and roots, a change in leaf morphology, the expansion of leaf surface area, and the shortening of the internodes. A number of ABA-responsive heterophylly (ABRH) genes are induced early during the transition. Using optically pure isomers of ABA, it was found that both the natural S-(+)-ABA and the unnatural R-(-)-ABA are capable of inducing a heterophyllous switch and regulating ABRH gene expression. When dose responses are compared, the unnatural ABA gives stronger morphogenic effects than the natural ABA at the same concentration, it is effective at lower concentrations, and its optimal concentration is also lower compared with the natural ABA. Deuterium-labelled ABA enantiomers were used to trace the fate of applied ABA and to distinguish the applied compound and its metabolites from the endogenous counterparts. In tissues, the supplied (+)-ABA was metabolized principally to dihydrophaseic acid, while the supplied (-)-ABA was converted at a slower rate to 7'-hydroxy abscisic acid. Treatment with either enantiomer resulted in increased biosynthesis of ABA, as reflected in the accumulation of endogenous dihydrophaseic acid. Taken together, these results suggest two distinct mechanisms of action for (-)-ABA: either (-)-ABA is intrinsically active, or its activity is due to the stimulation of ABA biosynthesis.

BackgroundOpportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy.MethodsThe delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methylation-specific PCR in a training set (57 CIN2− and 43 cervical intraepithelial neoplasia ≥grade 3 (CIN3+) women), and the individual and combination gene sensitivities and specificities were determined. The detection accuracy of three algorithms combining gynecologic findings and genetic test results was then compared in a randomized case-control study comprising 449 women referred for colposcopic examination by gynecologists in the outpatient department of Xiangya Hospital between November 2011 and March 2013.ResultsSignificant association was observed between CIN3+ and methylated PAX1 or ZNF582 in combination with HPV16/18 (OR:15.52, 95 % CI:7.73–31.18). The sensitivities and specificities of methylated PAX1 or ZNF582 combined with HPV16/18 for CIN3+ women were 89.2 and 76.0 %, or 85.4 and 80.1 %, respectively. Of the three algorithms applied to cohort data and validated in the study, two indicated 100 % sensitivity in detecting cervical cancer and a low rate of referrals for colposcopy.ConclusionsThese algorithms might contribute to precise and objective cervical cancer diagnostics in the outpatient departments of hospitals in countries with high mortality and low screening rates or areas with uneven resource distribution.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0232-3) contains supplementary material, which is available to authorized users.

PAX1 showed great potential as a biomarker for cervical cancer screening. When incorporating PAX1 detection into current screening protocol, the efficacy of screening could be greatly improved. Moreover, unnecessary referral for colposcopy and biopsy could be reduced up to 60%. However, prospective population-based studies are necessary for further implementation of this screening program.

Hypermethylated ZNF582 and PAX1 genes in oral epithelial cells collected by mouth rinse are effective biomarkers for the detection of oral dysplasia and oral cancer.