英語関係代名詞whichの機能と習得 : コーパスに基づく記述的研究

<div><p></p><p>An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing <i>in vivo</i> NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO₂) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO₂ from lungs.</p></div

Thyroid Hormone Response Element Half-Site Organization and Its Effect on Thyroid Hormone Mediated Transcription

<div><p>Thyroid hormone (TH) exerts its effects by binding to the thyroid hormone receptor (TR), which binds to TH response elements (TREs) to regulate target gene expression. We investigated the relative ability of liganded homodimers TR and retinoid X receptor (RXR), and the heterodimer TR/RXR, to regulate gene expression for the TRE half-site organizations: direct repeat 4 (DR4), inverted repeat 0 (IR0) and everted repeat 6 (ER6). Luciferase reporter assays using a DR4 TRE suggest that both the TR homodimer and TR/RXR heterodimer regulate luciferase expression in the presence of their respective ligands. However, in the presence of the IR0 TRE, transfection with TR/RXR and RXR alone increased luciferase activity and there was no effect of TR alone. The presence of 9-cis-retinoic acid was necessary for luciferase expression, whereas TH treatment alone was insufficient. For the ER6 TRE, transfection with TR/RXR, TR alone and RXR alone (in the presence of their respective ligands) all caused a significant increase in luciferase activity. When both ligands were present, transfection with both TR/RXR caused more activation. Finally, we investigated the efficacy of the TR-antagonist 1–850 in inhibiting transcription by TR or TR/RXR at DR4 and ER6 TREs. We found that 1–850 did not suppress luciferase activation in the presence of TR/RXR for the ER6 TRE, suggesting conformational changes of the ligand binding domain of the TR when bound to different TRE half-site organizations. Collectively, the findings indicate that there are fundamental differences between TRE configurations that affect nuclear receptor interactions with the response element and ability to bind ligands and antagonists.</p></div

Half-site organization for TRE constructs.

<p>Half-sites are in bold and the underlined sequences are the endonuclease sites (Xho I on left and Hind III on right) showing where the oligonucleotide was inserted into the plasmid.</p

Antagonistic effects of 1–850 determined by luciferase reporter assay for DR4 (A) and ER6 (B).

<p>COS-7 cells were co-transfected with a TRα or TRα+RXRα expression vectors. Cells were treated with or without 5 nM T3, or with T3 in the presence of 10 µM 1–850. Firefly luciferase expression was normalized to renilla luciferase expression. Experiments were run in triplicate and repeated at least 3 times. Data are presented as means ± standard error of the mean. Asterisks (*) denote a significant difference, p≤0.05, determined by one way ANOVA followed by Tukey's HSD test; (ns) denote no significant difference, p≥0.05.</p

BMDExpress Data Viewer A Visualization Tool to Analyze BMDExpress Datasets

BMDExpress Data Viewer A Visualization Tool to Analyze BMDExpress Dataset

Top Biological Functions and Diseases identified through IPA on day 2 and day 4 following treatment with BPA or BPS (p<0.05).

<p>Top Biological Functions and Diseases identified through IPA on day 2 and day 4 following treatment with BPA or BPS (p<0.05).</p

Top differentially expressed genes with the largest fold changes on day 2 and day 4 following treatment with BPA or BPS.

<p>False Discovery Rate (FDR)<0.05, -1.5 ≤ Fold-Change >1.5.</p

Regulatory network analysis using IPA.

<p>Regulatory network generated in IPA for genes that were differentially expressed following exposure to BPA (A, B) and BPS (C, D) on day 2 and day 4. Orange represents activated upstream regulator or biological process; Blue represents inhibited upstream regulator or biological process; Red indicates gene expression is up-regulated; Green indicates gene expression is down-regulated.</p

BPA, BPS and DEX treatments result in common and unique DEGs.

<p>The Venn diagram is showing overlap of significantly differentially expressed genes (-1.5 ≥fold change ≥ 1.5, FDR p ≤ 0.05) in human preadipocytes treated with BPA, BPS or DEX on Day 2 and Day 4. Venn diagrams were produced using the on-line tool Venny (<a href="http://bioinfogp.cnb.csic.es/tools/venny/" target="_blank">http://bioinfogp.cnb.csic.es/tools/venny/</a>).</p

Top Upstream Regulators identified through IPA on day 2 and day 4 following treatment with BPA or BPS (p<0.05).

<p>Top Upstream Regulators identified through IPA on day 2 and day 4 following treatment with BPA or BPS (p<0.05).</p