Treatment effects on neurometabolite levels in schizophrenia: A meta-analysis dataset of proton magnetic resonance spectroscopy

This article describes a dataset for a meta-analysis that aimed to investigate the effects of treatment on the neurometabolite status in patients with schizophrenia (DOI of original article: https://doi.org/10.1016/j.schres.2020.03.069 [1]). The data search was performed with MEDLINE, Embase, and PsycINFO. The neurometabolites investigated include glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, and myo-inositol, and the regions of interest (ROIs) include the frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, and hippocampus. The meta-analysis was conducted with a random-effects model, and the use of the standardized mean difference method between pre- and post-treatment of subjects for neurometabolites in each ROI of three patient groups or more. The dataset covers raw data of 39 patient groups (773 patients with schizophrenia at follow-up) with neurometabolite levels measured by magnetic resonance spectroscopy both before and after treatment. Furthermore, it contains details of clinical characteristics and treatment types for each group. Therefore, the data would be useful for a reinvestigation of treatment effects on the neurometabolite status from diverse points of view, as well as for the development of future treatment strategies for psychiatric diseases

Precise and Efficient Nucleotide Substitution Near Genomic Nick via Noncanonical Homology-Directed Repair

CRISPR/Cas9, which generates DNA double-strand breaks (DSBs) at target loci, is a powerful tool for editing genomes when codelivered with a donor DNA template. However, DSBs, which are the most deleterious type of DNA damage, often result in unintended nucleotide insertions/deletions (indels) via mutagenic nonhomologous end joining. We developed a strategy for precise gene editing that does not generate DSBs. We show that a combination of single nicks in the target gene and donor plasmid (SNGD) using Cas9D10A nickase promotes efficient nucleotide substitution by gene editing. Nicking the target gene alone did not facilitate efficient gene editing. However, an additional nick in the donor plasmid backbone markedly improved the gene-editing efficiency. SNGD-mediated gene editing led to a markedly lower indel frequency than that by the DSB-mediated approach. We also show that SNGD promotes gene editing at endogenous loci in human cells. Mechanistically, SNGD-mediated gene editing requires long-sequence homology between the target gene and repair template, but does not require CtIP, RAD51, or RAD52. Thus, it is considered that noncanonical homology-directed repair regulates the SNGD-mediated gene editing. In summary, SNGD promotes precise and efficient gene editing and may be a promising strategy for the development of a novel gene therapy approach

A new inelastic neutron spectrometer HODACA

A new multiplex-type inelastic neutron scattering spectrometer, HOrizontally Defocusing Analyzer Concurrent data Acquisition spectrometer (HODACA), was recently developed and built at the C1-1 cold neutron beam port in JRR-3. The spectrometer is suitable for dynamics measurements in the energy range of $-1$ meV $\lesssim \hbar \omega \lesssim$ 7 meV, catering to a broad array of research fields in physics and material science. HODACA combines 24 detectors and 132 pieces of analyzer crystals and has an estimated measurement efficiency that is 70 times greater than the existing conventional triple-axis spectrometer at the C1-1 beam port. The concept, design, specification, and results of commissioning experiments are described.Comment: 11 pages, 16 figure

Functional role and tobacco smoking effects on methylation of CYP1A1 gene in prostate cancer.

Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2'-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment

Glutamatergic neurometabolite levels in the caudate are associated with the ability of rhythm production

IntroductionGlutamatergic neurometabolites play important roles in the basal ganglia, a hub of the brain networks involved in musical rhythm processing. We aimed to investigate the relationship between rhythm processing abilities and glutamatergic neurometabolites in the caudate.MethodsWe aquired Glutamatergic function in healthy individuals employing proton magnetic resonance spectroscopy. We targeted the right caudate and the dorsal anterior cingulate cortex (dACC) as a control region. Rhythm processing ability was assessed by the Harvard Beat Assessment Test (H-BAT).ResultsWe found negative correlations between the production part of the Beat Saliency Test in the H-BAT and glutamate and glutamine levels in the caudate (r = −0.693, p = 0.002) whereas there was no such association in the dACC.ConclusionThese results suggest that higher glutamatergic neurometabolite levels in the caudate may contribute to rhythm processing, especially the ability to produce meter in music precisely

Wavelet analysis of transonic buffet on a two-dimensional airfoil with vortex generators

We visualized the shock buffets on a two-dimensional transonic airfoil with and without vortex generators (VGs) by using a fast-framing focusing schlieren imaging. The focusing schlieren visualization showed that the flow three-dimensionality around the airfoil became remarkable with installing the VGs. This implies that narrow depth of focus of imaging systems was a key to accurately capture the characteristics of the shock oscillation due to the buffet for the cases with VGs. The time-resolved imaging also revealed that non-periodic components were included in the shock oscillation due to the buffet for the cases with VGs. This prevented Fourier analysis from being applied. We used wavelet analysis to extract the characteristic of the shock oscillation for the cases with VGs. The wavelet spectrograms revealed that the low-frequency oscillation having the buffet frequency was still included intermittently in the shock oscillation even when VG controlled the buffet. The rate of appearing the low-frequency oscillation increased with increasing both the interval between VGs and the angle of attack

Zoledronate/Anti-VEGF Neutralizing Antibody Combination Administration Increases Osteal Macrophages in a Murine Model of MRONJ Stage 0-like Lesions

The pathophysiology, pathogenesis, histopathology, and immunopathology of medicationrelated osteonecrosis of the jaw (MRONJ) Stage 0 remain unclear, although 50% of MRONJ Stage 0 cases could progress to higher stages. The aim of this study was to investigate the effects of zoledronate (Zol) and anti-vascular endothelial cell growth factor A (VEGFA) neutralizing antibody (Vab) administration on polarization shifting of macrophage subsets in tooth extraction sockets by creating a murine model of MRONJ Stage 0-like lesions. Eight-week-old, female C57BL/6J mice were randomly divided into 4 groups: Zol, Vab, Zol/Vab combination, and vehicle control (VC). Subcutaneous Zol and intraperitoneal Vab administration were performed for 5 weeks with extraction of both maxillary first molars 3 weeks after drug administration. Euthanasia was conducted 2 weeks after tooth extraction. Maxillae, tibiae, femora, tongues, and sera were collected. Structural, histological, immunohistochemical, and biochemical analyses were comprehensively performed. Tooth extraction sites appeared to be completely healed in all groups. However, osseous healing and soft tissue healing of tooth extraction sites were quite different. The Zol/Vab combination significantly induced abnormal epithelial healing, and delayed connective tissue healing due to decreased rete ridge length and thickness of the stratum granulosum and due to decreased collagen production, respectively. Moreover, Zol/Vab significantly increased necrotic bone area with increased numbers of empty lacunae compared with Vab and VC. Most interestingly, Zol/Vab significantly increased the number of CD169+ osteal macrophages (osteomacs) in the bone marrow and decreased F4/80+ macrophages, with a slightly increased ratio of F4/80+CD38+ M1 macrophages compared to VC. These findings are the first to provide new evidence of the involvement of osteal macrophages in the immunopathology of MRONJ Stage 0-like lesions

Versatile Biaryls and Fused Aromatics through Oxidative Coupling of Hydroquinones with (Hetero)Arenes

Aijima T., Ueda R., Nakane T., et al. Versatile Biaryls and Fused Aromatics through Oxidative Coupling of Hydroquinones with (Hetero)Arenes. ChemistrySelect 9, e202400647 (2024); https://doi.org/10.1002/slct.202400647.Hydroquinones bearing an electron-withdrawing group at the C2-position can effectively underwent oxidative coupling with (hetero)arenes (e. g., indoles, electron-rich benzene derivatives) in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and FeCl3 to produce the corresponding biaryl products. In the present reactions, the DDQ-mediated oxidation of hydroquinone derivatives produce benzoquinone intermediate, which subsequently underwent FeCl3-catalyzed nucleophilic addition of (hetero)arenes to the α,β-unsaturated carbonyl moiety to give the biaryl product in a one-pot manner. Especially, the indole-based biaryl products were further converted into tetracyclic aromatics through DDQ-mediated oxidation followed by FeCl3-catalyzed intramolecular cyclization. Thiophene derivatives were also applicable to give the tetracyclic aromatics. Moreover, the photophysical properties of the indole- and thiophene-based tetracyclic aromatics in the solution and the solid states were investigated

Positron emission tomography assessments of phosphodiesterase 10A in patients with schizophrenia

[Background and hypothesis] Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels. [Study design] This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy. [Study results] Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group. [Conclusions] The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia