A novel series of methoxy-trans-stilbenes with 3,4-dimethoxy motifs was designed and synthesized. The inhibitory potency of 3,4-dimethoxystilbene derivatives against cytochrome P450 isozymes CYP1A1, CYP1B1 and CYP1A2 was evaluated. 3,4,2 0 -Trimethoxy-trans-stilbene (3,4,2 0 -TMS) exhibited extremely potent inhibitory action against CYP1B1 activity with an IC 50 of 0.004 mM. 3,4,2 0 -TMS exhibited 90-fold selectivity for CYP1B1 over CYP1A1 and 830-fold selectivity for CYP1B1 over CYP1A2. However, 3,4,2 0 ,4 0tetramethoxy-trans-stilbene appeared to be the most selective inhibitor of both CYP1B1 and CYP1A1showing very low affinity toward CYP1A2. Complementary experimental studies and computational methods were used to explain what structural determinants decide the specific affinity of stilbene derivatives to CYP1A2 and CYP1B1 binding sites.

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All guanine-rich DNA and RNA molecules tend to fold into inter-and intra-molecular structures called G-quadruplexes. The core of a G-quadruplex is composed of at least two adjacent G-tetrads stabilized by monovalent cations. While it has been suggested that there could potentially be over 375 000 quadruplex forming sequences in the human genome alone, only a small number of three-dimensional G-quadruplex structures are known. More structural data are needed to explain their presence and function in vivo. We offer here a short review of experimental methods commonly used to determine G-quadruplex topologies.

Purpose Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany. Methods Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X. Follow-up to determine clinical truth was carried out. Results Of the 13,607 cases, 13,509 received a NIPT call resulting in a low study failure rate of 0.72%. There were 188 (1.4%) high-risk calls: 117 trisomy 21, 34 trisomy 18, 23 trisomy 13, one trisomy 21 + 13, and 13 monosomy X. High sensitivities and specificities of ≥ 98.89% were reported for all four aneuploidy conditions. Of the high-risk cases, clinical follow-up data were available for 77.1% (145/188). Clinical follow-up of high-risk calls revealed an overall positive predictive value of 84.8% (potential range 65.4–88.3%). NIPT results were provided for samples across a range of fetal fractions, down to 2% fetal fraction. Conclusion The VeriSeq NIPT Solution v2 assay detected fetal chromosomal aneuploidies across a range of fetal fractions with high sensitivities and specificities observed based on known clinical outcomes, a high overall PPV, and a low failure rate.