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Time-resolved multicolor multimodal laser illumination. 561nm, 488nm, and 637nm lasers sequentially illuminate on wall in wide-field mode, holographic optical tweezers mode (i.e. local-field mode), and combined mode. Multiple lasers are controlled independently with only a single SLM in a time-resolved fashion

Effects of VRK2 (rs2312147) on White Matter Connectivity in Patients with Schizophrenia

<div><p>Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.</p></div

Tract-Based Spatial Statistics (TBSS) analysis showing significant differences in fractional anisotropy (FA) values between the rs2312147 CC genotype group and the CT/TT genotype group in patients with schizophrenia.

<p>Voxels demonstrating significant increases in FA values for the CC genotype group compared with the CT/TT genotype group are shown in red-yellow (TFCE-corrected p<0.05). Results are overlaid on the Montreal Neurologic Institute 1 mm template (Z = −20 to Z = 46) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000. Left-right orientation is according to radiological convention.</p

Regions showing significant increases of fractional anisotropy (FA) value in rs2312147 CC genotype group compared to CT/TT genotype group in patients with schizophrenia.

<p>Note: Permutation-based inference tool for nonparametric statistics, threshold-free cluster enhancement (TFCE) method was used. Number of permutation was 10,000. To further reduce the possibility of false-positive results, only clusters with more than 100 contiguous voxels were considered in the analysis.</p><p>CC/CT/TT, The genotypes of rs2312147.</p>a<p>Foci for significant differences are listed (TFCE-corrected p<0.05).</p>b<p>TFCE-corrected p value.</p

Characteristics of study subjects.

<p>CSF, Cerebrospinal Fluid; GM, gray matter; ICV, intracranial volume; SD, standard deviation; WM, white matter.</p>a<p>Pearson Chi-square test.</p

Comparison of the sociodemographic and clinical characteristics between rs2312147 genotype groups in patients with schizophrenia.

<p>CC/CT/TT, The genotypes of rs2312147; CSF, Cerebrospinal Fluid; DST, Digit Symbol Test; GM, gray matter; ICV, intracranial volume; IQ, intelligence quotient; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation.</p>a<p>Fisher’s exact test.</p>b<p>Antipsychotic medication dose of all patients equivalent to chlorpromazine at the time of scan.</p>c<p>Pearson Chi-square test.</p

Biosynthesis of (−)-5-Hydroxy-equol and 5‑Hydroxy-dehydroequol from Soy Isoflavone, Genistein Using Microbial Whole Cell Bioconversion

Equols are isoflavandiols formed by reduction of soy isoflavones such as daidzein and genistein by gut microorganisms. These phytoestrogens are of interest for their various biological effects. We report biosynthesis from genistein to (−)-5-hydroxy-equol in recombinant <i>E. coli</i> expressing three reductases (daidzein reductase DZNR, dihidrodaidzein reductase DHDR, tetrahydrodaidzein reductase THDR) and a racemase (dihydrodaidzein racemase, DDRC) originating from the gut bacterium, <i>Slackia isoflavoniconvertens</i>. The biosynthesized 5-hydroxy-equol proved as an optically negative enantiomer, nonetheless it displayed an inverse circular dichroism spectrum to (<i>S</i>)-equol. Compartmentalized expression of DZNR and DDRC in one <i>E. coli</i> strain and DHDR and THDR in another increased the yield to 230 mg/L and the productivity to 38 mg/L/h. If the last reductase was missing, the intermediate spontaneously dehydrated to 5-hydroxy-dehydroequol in up to 99 mg/L yield. This novel isoflavene, previously not known to be synthesized in nature, was also detected in this biotransformation system. Although (<i>S</i>)-equol favors binding to human estrogen receptor (hER) β over hERα, (−)-5-hydroxy-equol showed the opposite preference. This study provides elucidation of the biosynthetic route of (−)-5-hydroxy-equol and measurement of its potent antagonistic character as a phytoestrogen for the first time

Regions of significant fractional anisotropy (FA) reduction in patients with panic disorder (PD) without comorbidity (N = 36) compared to healthy control (HC) subjects (N = 27).

<p>Voxels demonstrating significantly (threshold-free cluster enhancement, p<0.05 family-wise error corrected) decreased FA values for the PD group than for the HC group are shown in red-yellow (Z = −5 to Z = 25). Further cluster details are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095279#pone-0095279-t002" target="_blank">Table 2</a>. Number of permutations was 5000. Left–right orientation is according to the radiological convention.</p

Regions of positive correlation between Beck Anxiety Inventory (BAI) scores and fractional anisotropy (FA) in patients with panic disorder (PD).

<p>Voxels demonstrating a significant positive correlation (threshold-free cluster enhancement, p<0.05 family-wise error corrected) between the BAI scores and FA values of the white matter clusters where a significant group difference was found are shown in blue-light blue (Z = −5 to Z = 25). Further cluster details are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095279#pone-0095279-t003" target="_blank">Table 3</a>. Number of permutations was 5000. Left–right orientation is according to the radiological convention.</p