One-Enzyme Triple Catalysis: Employing the Promiscuity of Horseradish Peroxidase for Synthesis and Functionalization of Well-Defined Polymers

We demonstrate a new concept in polymer chemistry that the promiscuity of enzymes, as represented by horseradish peroxidase, can be employed for RAFT polymerization and thiol–ene and Diels–Alder reactions to synthesize well-defined functional polymers, via three different catalytic reactions mediated by one single enzyme

Microarray Profiling and Co-Expression Network Analysis of Circulating lncRNAs and mRNAs Associated with Major Depressive Disorder

<div><p>LncRNAs, which represent one of the most highly expressed classes of ncRNAs in the brain, are becoming increasingly interesting with regard to brain functions and disorders. However, changes in the expression of regulatory lncRNAs in Major Depressive Disorder (MDD) have not yet been reported. Using microarrays, we profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood sampled from MDD patients as well as demographically-matched controls. Among these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed, 17 of which were documented as depression-related gene in previous studies. Gene Ontology (GO) and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to fundamental metabolic processes and neurodevelopment diseases. To investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we also constructed co-expression networks composed of the lncRNAs and mRNAs, which shows significant correlated patterns of expression. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of mRNAs as they have previously been reported associations with MDD. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in MDD using microarray technology. We identified circulating lncRNAs that are aberrantly expressed in MDD and the results suggest that lncRNAs may contribute to the molecular pathogenesis of MDD.</p></div

The top 15 lncRNAs with largest degree differences in MDD co-expression network compared with controls.

<p>ND: MDD group; NC: Control group; dir: direction of differential regulation in MDD compared to control; k: normalized degree; DiffK: difference between MDD and controls; |DiffK|: absolute value of DiffK.</p

Regions showing significant differences in fALFF between each of the two groups.

<p><b>(A)</b> demonstrates regions showing group difference between the BD and CON groups, with the fALFF value increased in BD relative to the controls. <b>(B</b>) demonstrates the region exhibiting group difference between the MDD and CON group, with the fALFF value increased in the CON group relative to MDD.<b>(C</b>) demonstrates regions showing group difference between the BD and MDD groups, with the fALFF value increased in BD relative to MDD. The color bar means the intensity of Z-value, yellow/red in the color bar denotes relatively higher fALFF values, and cyan /blue in the color bar denotes relatively higher fALFF values. Locations of the clusters showing group differences were indicated by Arabic numbers labeled in each image. The number in the lower right corner of each image refers to the z MNI coordinates. Brain region labels: 1. left putamen; 2. right putamen; 3. left superior frontal gyrus/medial frontal gyrus; 4. right putamen; 5. left putamen; 6. left superior frontal gyrus. Left in the figure indicates the right side of the brain. BD: bipolar disorder. MDD: major depression. CON: control.</p

Comparisons of mean fALFF value in each ROI across groups generated from post hoc analysis using Bonferroni correction.

<p>Distinct ROIs were presented in the X-axis. The Y-axis represented mean fALFF value of each ROI. A single asterisks means a significance level of p < 0.05, and double asterisks indicate a significance level of <i>p</i> <0.01. BD: bipolar disorder. MDD:. CON: control. L PUT BD-CON: left putamen resulted from BD vs. CON comparison; R PUT BD-CON: right putamen resulted from BD vs. CON comparison; L SFG MDD-CON: left SFG/medial frontal gyrus resulted from MDD vs. CON comparison; R PUT BD-MDD: right putamen resulted from BD vs. MDD comparison; L PUT BD-MDD: left putamen resulted from BD vs. MDD comparison; L SFG BD-MDD: left SFG resulted from BD vs. MDD comparison.</p

Comparison between microarray and quantitative real-time PCR results.

<p>Four differentially expressed lncRNAs were validated by qPCR. The heights of the columns in the chart represent the log-transformed median fold changes (MD/Control) in expression across ten samples (p<0.05).</p

Demographics and clinical characters for controls and patients with MDD.

<p>MDD: major depressive disorder. HAMD₁₇: 17 item Hamilton Depression rating scale.</p

Genes with previous associations to MDD represented among the differentially expressed genes identified in this study.

<p>MDD-associated genes are derived from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Lohoff1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Shyn1" target="_blank">[34]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Lewis1" target="_blank">[35]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Shi1" target="_blank">[36]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Lee1" target="_blank">[37]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Henningsen1" target="_blank">[38]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Teyssier1" target="_blank">[39]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Tordera1" target="_blank">[40]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Wong1" target="_blank">[41]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Yamada1" target="_blank">[42]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Seifuddin1" target="_blank">[43]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Consortium1" target="_blank">[44]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093388#pone.0093388-Tiwary1" target="_blank">[45]</a></p

Profiles of differentially expressed genes in MDD compared to controls.

<p>(A) Differentially expressed lncRNAs and (B) differentially expressed mRNAs were subjected to hierarchical clustering. Red color indicates high relative expression and green color indicates low relative expression.</p

Demographic and clinical characters for the BD, MDD and the Control group.

<p>Demographic and clinical characters for the BD, MDD and the Control group.</p