Function annotation of hepatic retinoid x receptor α based on genome-wide DNA binding and transcriptome profiling.

BackgroundRetinoid x receptor α (RXRα) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRα-null mouse livers, the current study identifies the bona-fide hepatic RXRα targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRα regulates hepatic genes is elucidated in a high-throughput manner.Principal findingsClose to 80% of hepatic expressed genes were bound by RXRα, while 16% were expressed in an RXRα-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRα binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRα-dependent genes revealed that hepatic RXRα deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXRα bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRα in regulating nuclear receptor-mediated pathways.ConclusionsThis study establishes the relationship between RXRα DNA binding and hepatic gene expression. RXRα binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRα dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRα in post-transcriptional regulation

Expression of bgt gene in transgenic birch (Betula platyphylla Suk.)

Study on the characteristics of integration and expression is the basis of genetic stability of foreign genes in transgenic trees. To obtain insight into the relationship of transgene copy number and expression level, we screened 22 transgenic birch lines. Southern blot analysis of the transgenic birch plants indicated that the copy number of bgt varies from one to four, of which 18.2% were single copy. Copy number of bgt and gus was different in 68% of transgenic birch plants, indicating that rearrangement or partial deletion appeared in the process of T-DNA integration. Transcriptional expression of bgt gene in transgenic birch plants was analyzed by Northern blot. TGS has been found in two transgenic lines with one and four copies of bgt. The ELISA result showed that the BGT protein expression level in the transgenic birch plants ranged from 0.000 to 0.283% of total soluble protein. In contrary to most studies, this research showed no significant correlation was found between copy number and expression level of bgt gene. Effective resistance of transgenic plants against Lymantria dispar was verified in feeding bioassays with the insects. Bioassays results were mostly consistent with the expression level of BGT insecticidal protein detected by ELISA and Western blot in transgenic birch. The paper showed transgenic birch had the high lethal effect on gypsy moth larvae (L. dispar). The practicality of this work will benefit not only the birch producers, but also the environment worldwide

Function Annotation of Hepatic Retinoid x Receptor α Based on Genome-Wide DNA Binding and Transcriptome Profiling

Background Retinoid x receptor α (RXRα) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRα-null mouse livers, the current study identifies the bona-fide hepatic RXRα targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRα regulates hepatic genes is elucidated in a high-throughput manner. Principal Findings Close to 80% of hepatic expressed genes were bound by RXRα, while 16% were expressed in an RXRα-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRα binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRα-dependent genes revealed that hepatic RXRα deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXRα bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRα in regulating nuclear receptor-mediated pathways. Conclusions This study establishes the relationship between RXRα DNA binding and hepatic gene expression. RXRα binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRα dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRα in post-transcriptional regulation.This work was supported by the National Institutes of Health (DK092100 and CA053596 to YYW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

3′,6′-Bis(diethyl­amino)-3H-spiro­[2-benzo­thio­phene-1,9′-xanthene]-3-thione

The title compound, C28H30N2OS2, was obtained by thio­nation of 3′,6′-bis­(diethyl­amino)-3H-spiro­[isobenzofuran-1,9′-xan­thene]-3-one with 2,4-bis­(p-methoxy­phen­yl)-1,3-dithia­diphos­phetane disulfide (Lawesson’s reagent). The planes of the two benzene rings of the xanthene system are inclined at a dihedral angle of 17.4 (1)°, and the plane of the dithio­phthalide group and the planes through the two benzene rings of the xanthene system make dihedral angles of 80.2 (1) and 82.8 (1)°, respectively

Polyketides from the Halotolerant Fungus Myrothecium sp. GS-17

Two new polyketides, myrothecol (1) and 5-hydroxy-3-methyl-4-(1- hydroxylethyl)-furan-2(5H)-one (2), were isolated from the fermentation broth of the halotolerant fungus Myrothecium sp. GS-17 along with three known compounds, 5-hydroxyl-3-[(1S)-1-hydroxyethyl]-4-methylfuran-2(5H)-one (3), 3,5-dimethyl-4- hydroxylmethyl-5-methoxyfuran-2(5H)-one (4), and 3,5-dimethyl-4-hydroxymethyl-5- hydroxyfuran-2(5H)-one (5). Compound 1 is the first natural occurring polyketide with a unique furylisobenzofuran skeleton. The structures of these compounds were established via extensive spectroscopic analyses including 1D-, 2D-NMR, HRESI-MS, and crystal X-ray diffraction analysis

Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC

Optoelectronic properties and ultrafast carrier dynamics of copper iodide thin films

As a promising high mobility p-type wide bandgap semiconductor, copper iodide has received increasing attention in recent years. However, the defect physics/evolution are still controversial, and particularly the ultrafast carrier and exciton dynamics in copper iodide has rarely been investigated. Here, we study these fundamental properties for copper iodide thin films by a synergistic approach employing a combination of analytical techniques. Steady-state photoluminescence spectra reveal that the emission at ~420 nm arises from the recombination of electrons with neutral copper vacancies. The photogenerated carrier density dependent ultrafast physical processes are elucidated with using the femtosecond transient absorption spectroscopy. Both the effects of hot-phonon bottleneck and the Auger heating significantly slow down the cooling rate of hot-carriers in the case of high excitation density. The effect of defects on the carrier recombination and the two-photon induced ultrafast carrier dynamics are also investigated. These findings are crucial to the optoelectronic applications of copper iodide