7 research outputs found
Alteration of Diastereoisomeric and Enantiomeric Profiles of Hexabromocyclododecanes (HBCDs) in Adult Chicken Tissues, Eggs, and Hatchling Chickens
The
concentrations and enantiomer fractions (EFs) of α-,
β-, and γ-hexabromocyclododecanes (HBCDs) were measured
in chicken diet sources (soil and chicken feed), home-raised adult
chicken (<i>Gallus domesticus</i>) tissues, eggs during
incubation, and hatchling chicken tissues. HBCD concentrations were
not detected–0.69 ng/g dry weight (dw) and 25.6–48.4
ng/g dw in chicken feed and soil, respectively. HBCDs were detected
in all adult chicken tissues, except the brain, at median levels of
13.1–44.0 ng/g lipid weight (lw). The proportions of α-HBCD
in total HBCDs increased from 51% in soil to more than 87% in adult
chicken tissues. The accumulation ratios (ARs) of α-HBCD from
diet to adult chicken tissues were 4.27 for liver, 11.2 for fat, and
7.64–12.9 for other tissues, respectively. The AR and carry-over
rate (COR) of α-HBCD from diet to eggs were 22.4 and 0.226,
respectively. The concentrations of α-HBCD in hatchling chicken
liver (median: 35.4 ng/g lw) were significantly lower than those in
hatchling chicken pectoral muscle (median: 130 ng/g lw). The EFs of
α-HBCD decreased from soil to adult chicken tissues and from
eggs to hatchling chicken liver. Meanwhile, the EFs of γ-HBCD
increased from soil to adult chicken tissues. These results indicate
the preferential enrichment of (−)-α-HBCD and (+)-γ-HBCD
in chickens. The alteration of diastereoisomeric and enantiomeric
patterns of HBCDs might be influenced by the different absorption
and elimination rates of the six HBCD enantiomers as well as variations
in HBCD metabolism in chickens
Large multicohort study reveals a prostate cancer susceptibility allele at 5p15 regulating TERT via androgen signaling-orchestrated chromatin binding of E2F1 and MYC
Abstract
Aberrant telomerase reverse transcriptase (TERT) expression is crucial for tumor survival and cancer cells escaping apoptosis. Multiple TERT-locus variants at 5p15 have been discovered in association with cancer risk, yet the underlying mechanisms and clinical impacts remain unclear. Here, our association studies showed that the TERT promoter variant rs2853669 confers a risk of prostate cancer (PCa) in different ethnic groups. Further functional investigation revealed that the allele-specific binding of MYC and E2F1 at TERT promoter variant rs2853669 associates with elevated level of TERT in PCa. Mechanistically, androgen stimulations promoted the binding of MYC to allele T of rs2853669, thereby activating TERT, whereas hormone deprivations enhanced E2F1 binding at allele C of rs2853669, thus upregulating TERT expression. Notably, E2F1 could cooperate with AR signaling to regulate MYC expression. Clinical data demonstrated synergistic effects of MYC/E2F1/TERT expression or with the TT and CC genotype of rs2853669 on PCa prognosis and severity. Strikingly, single-nucleotide editing assays showed that the CC genotype of rs2853669 obviously promotes epithelial–mesenchymal transition (EMT) and the development of castration-resistant PCa (CRPC), confirmed by unbiased global transcriptome profiling. Our findings thus provided compelling evidence for understanding the roles of noncoding variations coordinated with androgen signaling and oncogenic transcription factors in mis-regulating TERT expression and driving PCa