We demonstrate efficient nonlinear frequency conversion in atomic Pb vapor under conditions where the linear susceptibility and the effective nonlinear susceptibility are of the same order. This is accomplished by using electromagnetically induced transparency to prepare a near-maximal atomic coherence on a Raman transition. This strongly driven transition is used to convert an intense laser beam from 425 to 293 nm with an efficiency of ϳ40%. [S0031-9007(96)01644-4]

As transcriptional factors, nuclear receptors (NRs) function as major regulators of gene expression. In particular, dysregulation of NR activity has been shown to significantly alter metabolic homeostasis in various contexts leading to metabolic disorders and cancers. The orphan estrogen-related receptor (ERR) subfamily of NRs, comprised of ERRα, ERRβ, and ERRγ, for which a natural ligand has yet to be identified, are known as central regulators of energy metabolism. If AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) can be viewed as sensors of the metabolic needs of a cell and responding acutely via post-translational control of proteins, then the ERRs can be regarded as downstream effectors of metabolism via transcriptional regulation of genes for a long-term and sustained adaptive response. In this review, we will focus on recent findings centered on the transcriptional roles played by ERRα in hepatocytes. Modulation of ERRα activity in both in vitro and in vivo models via genetic or pharmacological manipulation coupled with chromatin-immunoprecipitation (ChIP)-on-chip and ChIP-sequencing (ChIP-seq) studies have been fundamental in delineating the direct roles of ERRα in the control of hepatic gene expression. These studies have identified crucial roles for ERRα in lipid and carbohydrate metabolism as well as in mitochondrial function under both physiological and pathological conditions. The regulation of ERRα expression and activity via ligand-independent modes of action including coregulator binding, post-translational modifications (PTMs) and control of protein stability will be discussed in the context that may serve as valuable tools to modulate ERRα function as new therapeutic avenues for the treatment of hepatic metabolic dysfunction and related diseases.

N-methyladenosine (mA), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated mA modification in multiple biological processes, but the function of mA has been difficult to study, because mutants are embryonic lethal in both mammals and plants. In this study, we have used transcription activator-like effector nucleases and generated viable zygotic mutant, Z , in zebrafish. We find that the oocytes in Z adult females are stalled in early development and the ratio of full-grown stage (FG) follicles is significantly lower than that of wild type. Human chorionic gonadotropin-induced ovarian germinal vesicle breakdown and the numbers of eggs ovulated are both decreased as well, while the defects of oocyte maturation can be rescued by sex hormone and In Z adult males, we find defects in sperm maturation and sperm motility is significantly reduced. Further study shows that 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels are significantly decreased in Z , and defective gamete maturation is accompanied by decreased overall mA modification levels and disrupted expression of genes critical for sex hormone synthesis and gonadotropin signaling in Z Thus, our study provides the first evidence that loss of Mettl3 leads to failed gamete maturation and significantly reduced fertility in zebrafish. Mettl3 and mA modifications are essential for optimal reproduction in vertebrates.