Statins, drugs commonly used to lower serum cholesterol, have been shown to stimulate osteoblast differentiation and bone formation. Statins inhibit 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase (HMGCR), the first step of the isoprenoid biosynthetic pathway, leading to the depletion of the isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The effects of s...

The purpose of this 2-week, double-blinded, controlled clinical trial was to evaluate the efficacy of topical amino acid-complexed zinc gluconate formulated with boric acid (ZGB) or acetic acid (ZGA) versus a topical placebo in the treatment of yeast otitis externa in dogs. Included in the study were dogs with otitis externa and a cytopathological finding of yeast organisms in the affected ear....

Abstract Extensive epigenetic reprogramming occurs during preimplantation embryo development. However, it remains largely unclear how the drastic contributes to transcriptional regulatory network this period. Here, we develop a single-cell multiomics sequencing technology (scNOMeRe-seq) that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in same ind...

In mammalian embryos, zygotic gene transcription initiates after a limited number of cell divisions through a two-step process termed the zygotic gene activation (ZGA). Here we report that RNA polymerase II undergoes major changes in mouse and rabbit preimplantation embryos during the ZGA. In transcriptionally inactive unfertilized oocytes, the RNA polymerase II largest subunit is predominantly...

Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify...

Zygotic genome activation (ZGA) is a major genome programming event whereby the cells of the embryo begin to adopt specified fates. Experiments in Drosophila and zebrafish have revealed that ZGA depends on transcription factors that provide large-scale control of gene expression by direct and specific binding to gene regulatory sequences. Zelda (Zld) plays such a role in the Drosophila embryo, ...

Abstract Cellular metabolism provides fundamental components for chromatin dynamics and epigenetics. However, metabolic features, their impact on epigenetic remodeling during mammalian pre-implantation development, remain poorly understood. In this study, we established the landscape of mouse embryos from zygote to blastocyst, quantified absolute carbohydrate metabolites. We found that amino ac...

Epigenetic modifications, such as DNA methylation and histone modifications, are dynamically altered predominantly in paternal pronuclei soon after fertilization. To identify which histone modifications are required for early embryonic development, we utilized histone K-M mutants, which prevent endogenous histone methylation at the mutated site. We prepared four single K-M mutants for histone H...

Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to th...