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The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on human DNMT1. Functional studies in human and mouse cells further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that preferentially occurs at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.

Abstract A numerical analysis is conducted for assessing the feasibility on the use of Global Navigation Satellite System (GNSS) receivers for Korea Positioning System (KPS) satellites in space service volume (SSV). KPS is planned to provide a navigation and timing service by constructing seven satellites over the Korean Peninsula, which will orbit above the GNSS constellation in SSV. The major problems caused by such orbital characteristics include reduced satellite visibility due to poor geometric diversity and weak signals, causing an increase in the user range error (URE). To address these constraints, this study considers multi‐GNSS and 1‐st side‐lobe signal utilization scenarios. More specifically, the GNSS satellite visibility, geometric dilution of precision, carrier‐to‐noise ratio, URE, and navigation error for KPS satellites in SSV are analysed through a numerical simulation. A trade‐off between visibility and received signal power as well as their effects on positioning accuracy is analysed to describe the utility of side‐lobe signals. Finally, based on numerical analysis of the simulation results, this verifies the applicability of GNSS SSV for KPS satellites through multi‐GNSS and side‐lobe utilization scenarios.

Abstract Recent advancements in next-generation sequencing (NGS) technologies have created new opportunities for comprehensive screening of multiple parasite species. In this study, we cloned the 18 S rDNA V9 region of 11 species of intestinal parasites into plasmids. Equal amounts and concentrations of these 11 plasmids were pooled, and amplicon NGS targeting the 18 S rDNA V9 region was performed using the Illumina iSeq 100 platform. A total of 434,849 reads were identified, and all 11 parasite species were detected, although the number of output reads for each parasite varied. The read count ratio, in descending order, was as follows: Clonorchis sinensis, 17.2%; Entamoeba histolytica, 16.7%; Dibothriocephalus latus, 14.4%; Trichuris trichiura, 10.8%; Fasciola hepatica, 8.7%; Necator americanus, 8.5%; Paragonimus westermani, 8.5%; Taenia saginata, 7.1%; Giardia intestinalis, 5.0%; Ascaris lumbricoides, 1.7%; and Enterobius vermicularis, 0.9%. We found that the DNA secondary structures showed a negative association with the number of output reads. Additionally, variations in the amplicon PCR annealing temperature affected the relative abundance of output reads for each parasite. These findings can be applied to improve parasite detection methodologies and ultimately enhance efforts to control and prevent intestinal parasitic infections.

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Abstract Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, “CNV neurons”), but previous analyses of CNV neurons are limited by relatively small sample sizes. Here, we develop an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We apply this approach to 2,125 frontal cortical neurons from a neurotypical human brain. SCOVAL identifies 226 CNV neurons, which include a subclass of 65 CNV neurons with highly aberrant karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we find that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contain fewer, but longer, genes.

Abstract We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Abstract The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.

Abstract Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGFβ), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)—a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.

Abstract The lateral septum (LS), a GABAergic structure located in the basal forebrain, is implicated in social behavior, learning, and memory. We previously demonstrated that expression of tropomyosin kinase receptor B (TrkB) in LS neurons is required for social novelty recognition. To better understand molecular mechanisms by which TrkB signaling controls behavior, we locally knocked down TrkB in LS and used bulk RNA-sequencing to identify changes in gene expression downstream of TrkB. TrkB knockdown induces upregulation of genes associated with inflammation and immune responses, and downregulation of genes associated with synaptic signaling and plasticity. Next, we generated one of the first atlases of molecular profiles for LS cell types using single nucleus RNA-sequencing (snRNA-seq). We identified markers for the septum broadly, and the LS specifically, as well as for all neuronal cell types. We then investigated whether the differentially expressed genes (DEGs) induced by TrkB knockdown map to specific LS cell types. Enrichment testing identified that downregulated DEGs are broadly expressed across neuronal clusters. Enrichment analyses of these DEGs demonstrated that downregulated genes are uniquely expressed in the LS, and associated with either synaptic plasticity or neurodevelopmental disorders. Upregulated genes are enriched in LS microglia, associated with immune response and inflammation, and linked to both neurodegenerative disease and neuropsychiatric disorders. In addition, many of these genes are implicated in regulating social behaviors. In summary, the findings implicate TrkB signaling in the LS as a critical regulator of gene networks associated with psychiatric disorders that display social deficits, including schizophrenia and autism, and with neurodegenerative diseases, including Alzheimer’s.

Abstract Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here.

We present microscopic cluster model calculations for the 1p and 2p decays of the 02+ and 22+ states of 10C. With the R-matrix method, we have estimated the decay widths. The obtained 1p and 2p decay widths are in good agreement with the recent experimental data and support the validity of the di-proton approximation for the 2p decay of 10C(02+). We also show the suppression of the 1p decay of the 10C(02+) state due to the structure mismatch with the decay channel.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid–Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

The effect of schizophrenia (SCZ) genetic risk on gene expression in brain remains elusive. A popular approach to this problem has been the application of gene co-expression network algorithms (e.g., WGCNA). To improve reliability with this method it is critical to remove unwanted sources of variance while also preserving biological signals of interest. In this WCGNA study of RNA-Seq data from postmortem prefrontal cortex (78 neurotypical donors, EUR ancestry), we tested the effects of SCZ genetic risk on co-expression networks. Specifically, we implemented a novel design in which gene expression was adjusted by linear regression models to preserve or remove variance explained by biological signal of interest (GWAS genomic scores for SCZ risk-(GS-SCZ), and genomic scores- GS of height (GS-Ht) as a negative control), while removing variance explained by covariates of non-interest. We calculated co-expression networks from adjusted expression (GS-SCZ and GS-Ht preserved or removed), and consensus between them (representative of a "background" network free of genomic scores effects). We then tested the overlap between GS-SCZ preserved modules and background networks reasoning that modules with reduced overlap would be most affected by GS-SCZ biology. Additionally, we tested these modules for convergence of SCZ risk (i.e., enrichment in PGC3 SCZ GWAS priority genes, enrichment in SCZ risk heritability and relevant biological ontologies. Our results highlight key aspects of GS-SCZ effects on brain co-expression networks, specifically: 1) preserving/removing SCZ genetic risk alters the co-expression modules; 2) biological pathways enriched in modules affected by GS-SCZ implicate processes of transcription, translation and metabolism that converge to influence synaptic transmission; 3) priority PGC3 SCZ GWAS genes and SCZ risk heritability are enriched in modules associated with GS-SCZ effects. Overall, our results indicate that gene co-expression networks that selectively integrate information about genetic risk can reveal novel combinations of biological pathways involved in schizophrenia.

Taeyoung Hwang et al. evaluate the relevance of Alu repeat elements to gliomagenesis using transcriptomic data from 41 pairs of neurotypical and diverse glioma brain tissues. Their results reveal that grade 2 oligodendroglioma differs from other gliomas with a higher proportion of perturbed Alu subfamilies and the minimally-affected overall A-to-I editing and circular RNA levels, providing further insight into gliomagenesis.

The present study aims to improve the mean extracted power of a Wave Energy Converter (WEC) by mapping the parameters of its ballast weight and position, wave frequency, viscosity, and Power Take-Off (PTO) damping using an Artificial Neural Network (ANN) model. A total of 25 types of WEC rotors are designed with varying ballast weights and positions. The hydrodynamic coefficient and response of each rotor are determined using linear potential theory and viscous damping is estimated using computational fluid dynamics. The optimal design parameters are obtained by applying the trained model to a large randomly generated input dataset and the prediction output is evaluated to determine the best design parameters. According to the findings of the study, a well-trained model can predict and adopt to the nonlinear behavior of the given dataset as well as provide the optimal design parameters for the selected pitch-type WEC rotor.

Well-characterized in chronic rhinosinusitis, type 2 inflammation is frequently associated with nasal polyps, comorbid asthma, and nonsteroidal anti-inflammatory drug hypersensitivity. Despite medical and surgical treatment, it recurs in a significant proportion of patients. Thus, severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps is the most difficult-to-treat phenotype of chronic rhinosinusitis. Recently, dupilumab, a monoclonal antibody against IL-4 receptor α, and omalizumab, a monoclonal antibody against immunoglobulin E, were approved for patients with chronic rhinosinusitis with nasal polyps in the United States, Europe, and Korea. Therefore, rhinologists should understand novel biologics and their use. Here, we provide a literature review of several biologics with their indications, effectiveness, and safety.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.

Abstract Background Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Results Here, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Conclusions This study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.

para-Phenylediamine (PPD), a major component of hair dyeing ingredients, can induce allergenic sensitization and exert mutagenic, tumorigenic and cytotoxic effect. In this study, we determined the cytotoxic effect of PPD on human keratinocytes and evaluated the protective effect of Rhus semialata M. extracts (RSE) on PPD induced cytotoxicity for the first time. We observed that RSE is a strong inhibitory agent against PPD-induced toxicity in human keratinocytes. The results indicated that RSE pretreatment significantly could suppress PPD induced cytotoxic effects, including decrease of cell viability, accumulation in subG1 phase of cells, and relocation of phosphatidylserine on keratinocytes. Also, we found that PPD caused cytotoxicity was associated with mitochondrial membrane potential loss and subsequent activation of caspase and PARP degradation. However, pretreatment of RSE showed preventive activities against PPD induced mitochondrial membrane potential loss and ROS production in keratinocytes. In conclusion, the results of present study suggest that RSE was able to protect the skin from several cytotoxic effects of PPD and could be a meaningful material in many industries using PPD.

Abstract Background While ETV6- NTRK3 fusion is common in infantile fibrosarcoma, NTRK1/3 fusion in pediatric tumors is scarce and, consequently, not well known. Herein, we evaluated for the presence of NTRK1/3 fusion in pediatric mesenchymal tumors, clinicopathologically and immunophenotypically. Methods We reviewed nine NTRK fusion-positive pediatric sarcomas confirmed by fluorescence in situ hybridization and/or next-generation sequencing from Seoul National University Hospital between 2002 and 2020. Results One case of TPR-NTRK1 fusion-positive intracranial, extra-axial, high-grade undifferentiated sarcoma (12-year-old boy), one case of LMNA-NTRK1 fusion-positive low-grade infantile fibrosarcoma of the forehead (3-year-old boy), one case of ETV6-NTRK3 fusion-positive inflammatory myofibroblastic tumor (IMT) (3-months-old girl), and six cases of ETV6-NTRK3 fusion-positive infantile fibrosarcoma (median age: 2.6 months, range: 1.6–5.6 months, M: F = 5:1) were reviewed. The Trk immunopositivity patterns were distinct, depending on what fusion genes were present. We observed nuclear positivity in TPR-NTRK1 fusion-positive sarcoma, nuclear membrane positivity in LMNA-NTRK1 fusion-positive sarcoma, and both cytoplasmic and nuclear positivity in ETV6-NTRK3 fusion-positive IMT and infantile fibrosarcomas. Also, the TPR-NTRK1 fusion-positive sarcoma showed robust positivity for CD34/nestin, and also showed high mitotic rate. The LMNA-NTRK1 fusion-positive sarcoma revealed CD34/S100 protein/nestin/CD10 coexpression, and a low mitotic rate. The IMT with ETV6-NTRK3 fusion expressed SMA. Six infantile fibrosarcomas with ETV6-NTRK3 fusion showed variable coexpression of nestin (6/6)/CD10 (4/5)/ S100 protein (3/6). Conclusions All cases of NTRK1 and NTRK3 fusion-positive pediatric tumors robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10/SMA immunohistochemical expression may suggest the presence of NTRK fusion partner genes. LMNA-NTRK1 fusion sarcoma might be a low-grade subtype of infantile fibrosarcoma. Interestingly, more than half of the infantile fibrosarcoma cases were positive for S100 protein and CD10. The follow-up period of TPR-NTRK1 and LMNA-NTRK1 fusion-positive tumors are not enough to predict prognosis. However, ETV6-NTRK3 fusion-positive infantile fibrosarcomas showed an excellent prognosis with no evidence of disease for an average of 11.7 years, after gross total resection of the tumor.

In this work, we successfully demonstrated In0.53Ga0.47As/InAs/In0.53Ga0.47As composite channel metamorphic high electron mobility transistors (mHEMTs) on a GaAs substrate. The fabricated mHEMTs with a 100 nm gate length exhibited excellent DC and logic characteristics such as VT = −0.13 V, gm,max = 949 mS/mm, subthreshold swing (SS) = 84 mV/dec, drain-induced barrier lowering (DIBL) = 89 mV/V, and Ion/Ioff ratio = 9.8 × 103 at a drain-source voltage (VDS) = 0.5 V. In addition, the device exhibited excellent high-frequency characteristics, such as fT/fmax = 261/304 GHz for the measured result and well-matched modeled fT/fmax = 258/309 GHz at VDS = 0.5 V, which is less power consumption compared to other material systems. These high-frequency characteristics are a well-balanced demonstration of fT and fmax in the mHEMT structure on a GaAs substrate.

Here, authors present results of a hiPSC transcriptomics study on corticogenesis from multiple donors across four transitions in differentiation. They present a bulk data deconvolution method and show that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation.

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial–mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-β1 (TGF-β1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-β1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-β1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract Recycled aggregates (RAs) production techniques are essential for the material circulation society because RAs from demolished concrete waste can sustainably be reused as a concrete material. However, RAs can bring about several performance decreases when they are used for recycled aggregate concrete (RAC) because of the low qualities (i.e., high water-absorption rate and low density) caused by the attached hydrated cement paste on the RA surface. Therefore, both the production of high-quality RAs and the surface modification of RAs are significantly important for the extension of RAC utilization. This paper focuses on the surface modification of RFA to reduce the water absorption rate and increase density. Hydrofluorosilicic acid (H2SiF6), which is one of the by-products in phosphoric acid manufacture, is used herein for the surface modification of the RFA. The physical properties and mechanical performance of mortar using RFA were evaluated after RFA modification. Consequently, the proposed method is effective in reducing water absorption rate and increasing density of RFA. The density of RFAs was slightly increased by 0.5–2.6% after modification. On the other hand, the water absorption rate decreased by 4–18% after modification. The compressive strengths of mortar at 28 days ages showed 18.1 MPa with modified RFA and 16.2 MPa with RFA.

Abstract Calcium acetate, which can be used in concrete to shorten the construction period and to improve productivity, was manufactured using limestone sludge and acetic acid. Calcium acetate contains a carboxyl group, and it can provide anticorrosive properties by forming a complex with the steel surface. We evaluated the basic performance of a carboxylic early-strength agent produced from industrial by-products (limestone sludge and acetic acid) as a corrosion inhibitor. A comparative evaluation was performed using calcium nitrate, which is a conventional early-strength agent; the corrosion area ratio, corrosion state, and electrochemical performance of a steel plate immersed in aqueous solutions were evaluated. A steel plate immersed in calcium acetate was not substantially corroded. The electrochemical investigations showed a high corrosion potential based on the impedance characteristics. The corrosion current showed anodic values, and no corrosion occurred on the surface of the steel plate because of the adsorption of carboxyl groups. Scanning electron microscopy indicated that the steel plate was covered by a crystalline coating, which suppressed corrosion. We show that it is possible to develop an environmentally friendly recycling method as an early-strength agent and corrosion inhibitor when manufacturing calcium acetate using limestone sludge.

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.

The present study aims to investigate the immunomodulatory effects of essential oil from Chamaecyparis obtusa (EOCO) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. BALB/c mice were intraperitoneally sensitized and stimulated with OVA. From day 22 to 35, 0.01% and 0.1% ECOC was intranasally administered 1 h before OVA stimulation. Nasal symptoms, as well as serum total and OVA-specific immunoglobulin (Ig) E levels, were measured. Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and their production by activated splenocytes were measured. Histological changes in the sinonasal mucosa were evaluated through hematoxylin and eosin and periodic acid-Schiff staining procedure. Th cytokines and their transcription factor mRNA expressions were determined using reverse-transcription polymerase chain reaction. Intranasal EOCO administration significantly suppressed allergic symptoms, OVA-specific IgE level, sinonasal mucosal inflammatory cell infiltration, and mucus-producing periodic acid-Schiff (PAS) positive cell count. EOCO also significantly inhibited IL-4, IL-10, and TNF-α levels in NLF and activated splenocytes. Th2 and Treg related cytokines and their transcription factors in sinonasal mucosa were significantly suppressed through intransal EOCO instillation. In conclusion, repetitive EOCO intranasal instillation showed anti-inflammatory and anti-allergic effects by suppressing nasal symptoms and inhibiting the production and expression of inflammatory mediators in the OVA-induced AR mouse model.

BackgroundOf the 108 Schizophrenia (SZ) risk-loci discovered through genome-wide association studies (GWAS), 96 are not altering the sequence of any protein. Evidence linking non-coding risk-SNPs and genes may be established using expression quantitative trait loci (eQTL). However, other approaches such allelic expression quantitative trait loci (aeQTL) also may be of use.MethodsWe applied both the eQTL and aeQTL analysis to a biobank of deeply sequenced RNA from 680 dorso-lateral pre-frontal cortex (DLPFC) samples. For each of 340 genes proximal to the SZ risk-SNPs, we asked how much SNP-genotype affected total expression (eQTL), as well as how much the expression ratio between the two alleles differed from 1:1 as a consequence of the risk-SNP genotype (aeQTL).ResultsWe analyzed overlap with comparable eQTL-findings: 16 of the 30 risk-SNPs known to have gene-level eQTL also had gene-level aeQTL effects. 6 of 21 risk-SNPs with known splice-eQTL had exon-aeQTL effects. 12 novel potential risk genes were identified with the aeQTL approach, while 55 tested SNP-pairs were found as eQTL but not aeQTL. Of the tested 108 loci we could find at least one gene to be associated with 21 of the risk-SNPs using gene-level aeQTL, and with an additional 18 risk-SNPs using exon-level aeQTL.ConclusionOur results suggest that the aeQTL strategy complements the eQTL approach to susceptibility gene identification.

Reinforcing steel maintains passivity in an alkaline concrete environment. However, the passive film on the steel can be destroyed as the concrete becomes acidic, which could induce the corrosion of reinforcing steel. Carbonates and sulfates destroy the concrete matrix and accelerate the penetration of hazardous ions, thereby deteriorating the structure. To alleviate the corrosion of internal reinforcing steel within concrete, corrosion inhibitors are most widely used. In this study, the effects of inorganic nitrite (lithium nitrite) and amino acid corrosion inhibitors (diethanolamine, methyl diethanolamine, and 4-aminobutyric) on corrosion resistance and the pH of the solution with various concentrations of Na2SO4 (0.89, 1.77 g/L) in saturated Ca(OH)2 that contained NaCl (0.98 g/L), which simulated the concrete environment, were investigated. The corrosion resistance of inhibitors was evaluated by corrosion potential, electrochemical impedance spectroscopy, and potentiodynamic techniques. The results indicated improvement of corrosion resistance by the addition of amino acid corrosion inhibitors. It was confirmed that the inhibitor adsorbed on the surface of the specimen and passivated to reduce the corrosion reaction. In addition, the 4-aminobutyric acid corrosion inhibitors had the corrosion protection efficiency of 67.87–77.80%, which is a higher value than that of the inorganic nitrite corrosion inhibitor (lithium nitrite: 69.36–75.93%) and other amino acid corrosion inhibitors (diethanolamine: 35.69–39.91%; methyl diethanolamine: 66.07–69.09%).