Prescription patterns of benzodiazepine and benzodiazepine-related drugs in the peripartum period: A population-based study

Using prescription drugs during pregnancy is challenging and approached with caution. In this study, we present population-based information on prescription patterns of benzodiazepines and benzodiazepine-related drugs in the peripartum period. A population-based study of 1,154,817 pregnancies between 1997 and 2015 in Denmark, of which 205,406 (17.8%) pregnancies in women with a psychiatric history. Prescription drugs starting with Anatomical Therapeutic Chemical codes N05BA, N05CD, and N05CF from 12 months before pregnancy to 12 months following pregnancy were identified. We used generalised estimating equations to estimate the adjusted 5 year risk difference in the proportion of women redeeming benzodiazepines from 1 year to 5 years after. Logistic regression was used to analyze the association between characteristics and discontinuation of benzodiazepines during pregnancy. The prevalence of benzodiazepine prescriptions was 1.9% before pregnancy, 0.6% during pregnancy, and 1.3% after pregnancy. In women with a psychiatric history, the prevalence was 5–6 times higher. A significant decrease in prescriptions to women with a psychiatric history was observed, which was less profound among women with no psychiatric history. Approximately 90% of women discontinue benzodiazepines during pregnancy, with a higher percentage of women discontinuing from 1997 to 2015. The observed decrease is likely explained by changing treatment guidelines

CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse

Diversified histone modifications (HMs) are essential epigenetic features. They play important roles in fundamental biological processes including transcription, DNA repair and DNA replication. Chromatin regulators (CRs), which are indispensable in epigenetics, can mediate HMs to adjust chromatin structures and functions. With the development of ChIP-Seq technology, there is an opportunity to study CR and HM profiles at the whole-genome scale. However, no specific resource for the integration of CR ChIP-Seq data or CR-HM ChIP-Seq linkage pairs is currently available. Therefore, we constructed the CR Cistrome database, available online at http://compbio.tongji.edu.cn/cr and http://cistrome.org/cr/, to further elucidate CR functions and CR-HM linkages. Within this database, we collected all publicly available ChIP-Seq data on CRs in human and mouse and categorized the data into four cohorts: the reader, writer, eraser and remodeler cohorts, together with curated introductions and ChIP-Seq data analysis results. For the HM readers, writers and erasers, we provided further ChIP-Seq analysis data for the targeted HMs and schematized the relationships between them. We believe CR Cistrome is a valuable resource for the epigenetics community

Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes

<p>Abstract</p> <p>Background</p> <p>The orphan nuclear receptor TR4 (human testicular receptor 4 or NR2C2) plays a pivotal role in a variety of biological and metabolic processes. With no known ligand and few known target genes, the mode of TR4 function was unclear.</p> <p>Results</p> <p>We report the first genome-wide identification and characterization of TR4 <it>in vivo </it>binding. Using chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq), we identified TR4 binding sites in 4 different human cell types and found that the majority of target genes were shared among different cells. TR4 target genes are involved in fundamental biological processes such as RNA metabolism and protein translation. In addition, we found that a subset of TR4 target genes exerts cell-type specific functions. Analysis of the TR4 binding sites revealed that less than 30% of the peaks from any of the cell types contained the DR1 motif previously derived from <it>in vitro </it>studies, suggesting that TR4 may be recruited to the genome via interaction with other proteins. A bioinformatics analysis of the TR4 binding sites predicted a <it>cis </it>regulatory module involving TR4 and ETS transcription factors. To test this prediction, we performed ChIP-seq for the ETS factor ELK4 and found that 30% of TR4 binding sites were also bound by ELK4. Motif analysis of the sites bound by both factors revealed a lack of the DR1 element, suggesting that TR4 binding at a subset of sites is facilitated through the ETS transcription factor ELK4. Further studies will be required to investigate the functional interdependence of these two factors.</p> <p>Conclusions</p> <p>Our data suggest that TR4 plays a pivotal role in fundamental biological processes across different cell types. In addition, the identification of cell type specific TR4 binding sites enables future studies of the pathways underlying TR4 action and its possible role in metabolic diseases.</p

Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton

Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to regulate cell polarity and directional cell migration

Different ionization mechanisms in pulsed micro-DBD’s in argon at different pressures

In this research we analyse different plasma wave propagation mechanism of microcavity discharge in pure argon at two different pressures. Experimental results of a pulsed micro-DBD with 2 and 50 kPa argon, 180 μm gap, at room temperature, show that two distinct pressure-dependent propagation modes exist. In the low pressure regime, the discharge propagates perpendicular to the applied electric field forming distinct channels, but many vertically-oriented filaments distributed throughout the domain at high pressure discharge. And the discharge duration time in high pressure is around 5 times shorter than that in low pressure. A 2D particle-in-cell (PIC-MCC) model with chemical reactions, photoemission, and secondary electron generation, is established to investigate the formation mechanism of the two propagation modes. Models of the initial ionization processes show that there are two different breakdown mechanisms for these two pressures, where secondary emission of electrons from the dielectric is dominated either by ion impact or by photon impact. The investigation is of great significance for further reveal of the principle of microplasmas discharge

Optically manipulating spins in semiconductor quantum dots

Physics considered here is the active control of a quantum system and of its decoherence by its environment. The relevance is in the quantum nature of nanoscience and how coherent optics in semiconductor quantum dots can contribute to quantum control. This article reviews: (1) The more recent theory of control of a set of dot spins through cavity quantum electrodynamics and (2) the quantum basis for control of decoherence of the electron spin interacting with the nuclei in the quantum dot. © 2007 American Institute of Physics.link_to_subscribed_fulltex

Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β

Isoorientin has anti-inflammatory effects; however, the mechanism remains unclear. We previously found isoorientin is an inhibitor of glycogen synthase kinase 3β (GSK3β) in vitro. Overactivation of GSK3β is associated with inflammatory responses. GSK3β is inactivated by phosphorylation at Ser9 (i.e., p-GSK3β). Lithium chloride (LiCl) inhibits GSK3β and also increases p-GSK3β (Ser9). The present study investigated the anti-inflammatory effect and mechanism of isoorientin via GSK3β regulation in lipopolysaccharide- (LPS-) induced RAW264.7 murine macrophage-like cells and endotoxemia mice. LiCl was used as a control. While AKT phosphorylates GSK3β, MK-2206, a selective AKT inhibitor, was used to activate GSK3β via AKT inhibition (i.e., not phosphorylate GSK3β at Ser9). The proinflammatory cytokines TNF-α, IL-6, and IL-1β were detected by ELISA or quantitative real-time PCR, while COX-2 by Western blotting. The p-GSK3β and GSK3β downstream signal molecules, including NF-κB, ERK, Nrf2, and HO-1, as well as the tight junction proteins ZO-1 and occludin were measured by Western blotting. The results showed that isoorientin decreased the production of TNF-α, IL-6, and IL-1β and increased the expression of p-GSK3β in vitro and in vivo, similar to LiCl. Coadministration of isoorientin and LiCl showed antagonistic effects. Isoorientin decreased the expression of COX-2, inhibited the activation of ERK and NF-κB, and increased the activation of Nrf2/HO-1 in LPS-induced RAW264.7 cells. Isoorientin increased the expressions of occludin and ZO-1 in the brain of endotoxemia mice. In summary, isoorientin can inhibit GSK3β by increasing p-GSK3β and regulate the downstream signal molecules to inhibit inflammation and protect the integrity of the blood-brain barrier and the homeostasis in the brain