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Background Identification of molecular signatures from omics studies is widely applied in toxicological studies, and the evaluation of potential toxic effects provides novel insights into molecular resolution. Objective The prediction of toxic effects and drug tolerance provides important clues regarding the mode of action of target compounds. However, heterogeneity within samples makes toxicology studies challenging because the purity of the target cell in the samples remains unknown until their actual utilization. Result Single-cell resolution studies have been suggested in toxicogenomics, and several studies have explained toxic effects and drug tolerance using heterogeneous cells in both in vivo and in vitro conditions. In this review, we presented an understanding of single-cell transcriptomes and their applications in toxicogenomics. Conclusion The most toxicological mechanism in organisms occurs through intramolecular combinations, and heterogeneity issues have reached a surmountable level. We hope this review provides insights to successfully conduct future studies on toxicology. Purpose of the review Toxicogenomics is an interdisciplinary field between toxicology and genomics that was successfully applied to construct molecular profiles in a broad spectrum of toxicology. However, heterogeneity within samples makes toxicology studies challenging because the purity of target cell in the samples remains unknown until their actual utilisation. In this review, we presented an understanding of single-cell transcriptomes and their applications in toxicogenomics. Recent findings A high-throughput techniques have been used to understand cellular heterogeneity and molecular mechanisms at toxicogenomics. Single-cell resolution analysis is required to identify biomarkers of explain toxic effect and in order to understand drug tolerance.

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

BACKGROUND Varicella zoster virus (VZV) is a human neurotropic and double-stranded DNA alpha-herpes virus. Primary infection with VZV usually occurs during childhood, manifesting as chickenpox. Reactivation of latent VZV can lead to various neurological complications, including transverse myelitis (TM); although cases of the latter are very rare, particularly in newly active VZV infection. CASE SUMMARY We report here an unusual case of TM in a middle-aged adult immunocompetent patient that developed concomitant to an active VZV infection. The 46-year-old male presented with painful vesicular eruption on his left chest that had steadily progressed to involvement of his back over a 3-d period. Cerebrospinal fluid testing was denied, but findings from magnetic resonance imaging and collective symptomology indicated TM. He was administered antiviral drugs and corticosteroids immediately but his symptom improvement waxed and waned, necessitating multiple hospital admissions. After about a month of repeated treatments, he was deemed sufficiently improved for hospital discharge to home. CONCLUSION VZV myelitis should be suspected when a patient visits the outpatient pain clinic with herpes zoster showing neurological symptoms.

The AHNAK nucleoprotein has been determined to exert an anti-obesity effect in adipose tissue and further inhibit adipogenic differentiation. In this study, we examined the role of AHNAK in regulating hepatic lipid metabolism to prevent diet-induced fatty liver. Ahnak KO mice have reportedly exhibited reduced fat accumulation in the liver and decreased serum triglyceride (TG) levels when provided with either a normal chow diet or a high-fat diet (HFD). Gene expression profiling was used to identify novel factors that could be modulated by genetic manipulation of the Ahnak gene. The results revealed that fibroblast growth factor 21 (FGF21) was markedly increased in the livers of Ahnak KO mice compared with WT mice fed a HFD. Ahnak knockdown in hepatocytes reportedly prevented excessive lipid accumulation induced by palmitate treatment and was associated with increased secretion of FGF21 and the expression of genes involved in fatty acid oxidation, which are primarily downstream of PPARα. These results indicate that pronounced obesity and hepatic steatosis are attenuated in HFD-fed Ahnak KO mice. This may be attributed, in part, to the induction of FGF21 and regulation of lipid metabolism, which are considered to be involved in increased fatty acid oxidation and reduced lipogenesis in the liver. These findings suggest that targeting AHNAK may have beneficial implications in preventing or treating hepatic steatosis., Liver disease: A potential treatment for nonalcoholic fatty liver A protein that modulates lipid accumulation could be a target for controlling nonalcoholic fatty liver disease (NAFLD). The AHNAK protein regulates fat cell development, and mice lacking AHNAK are less susceptible to obesity after being fed a HFD. South Korean researchers led by Je Kyung Seong of Seoul National University and Yun Soo Bae of Ewha Womans University, Seoul, have identified a mechanism by which AHNAK inhibition prevents lipid accumulation in NAFLD. The authors profiled gene expression in AHNAK-deficient mice, and noted a striking increase in levels of a signaling protein called FGF21 in the liver. This elevated FGF21 was in turn linked to increased breakdown and reduced production of fatty acids. Therapeutic interventions that inhibit AHNAK could help control NAFLD, a hard-to-treat condition that can ultimately lead to cirrhosis and liver failure.

Graphical abstract, Researchers have gained new therapeutic insights using multi-omics platform approaches to study DNA, RNA, and proteins of comprehensively characterized human cancer cell lines. To improve our understanding of the molecular features associated with oncogenic modulation in cancer, we proposed a proteogenomic database for human cancer cell lines, called Protein-gene Expression Nexus (PEN). We have expanded the characterization of cancer cell lines to include genetic, mRNA, and protein data of 145 cancer cell lines from various public studies. PEN contains proteomic and phosphoproteomic data on 4,129,728 peptides, 13,862 proteins, 7,138 phosphorylation site-associated genomic variations, 117 studies, and 12 cancer. We analyzed functional characterizations along with the integrated datasets, such as cis/trans association for copy number alteration (CNA), single amino acid variation for coding genes, post-translation modification site variation for Single Amino Acid Variation, and novel peptide expression for noncoding regions and fusion genes. PEN provides a user-friendly interface for searching, browsing, and downloading data and also supports the visualization of genome-wide association between CNA and expression, novel peptide landscape, mRNA-protein abundance, and functional annotation. Together, this dataset and PEN data portal provide a resource to accelerate cancer research using model cancer cell lines. PEN is freely accessible at http://combio.snu.ac.kr/pen.

Tight junction protein 1 (TJP1) is a membrane-associated cytosolic protein important for cell-cell communication in intercellular barriers in epithelial and non-epithelial cells. Here, we explored the functional involvement of TJP1 in non-epithelial tumors such as soft tissue sarcoma, especially in leiomyosarcoma (LMS). TJP1 expression in soft tissue sarcoma was analyzed in normal and tumor tissues as well as from public datasets such as the TCGA provisional dataset, in which TJP1 expression was compared with other subtypes such as undifferentiated sarcomas, and myxofibrosarcomas. SK-LMS-1 cell lines with reduced TJP1 expression showed attenuated anchorage-independent colony formation as well as reduced intercellular aggregation on non-coated culture plates compared with control as well as parental SK-LMS-1 cells. Transcriptome profiling following TJP1 knockdown in SK-LMS-1 cells suggested the involvement of several signaling pathways, including NF-κB pathway and growth factor receptor signaling. In addition, TJP1 downregulation induced enhanced response against anti-cancer agents, doxorubicin and gefitinib. Taken together, these results suggest that TJP1 contributes to sarcoma genesis and might be useful therapeutic target. KEY MESSAGES: • TJP1 expression at RNA level higher in tumor than in normal tissues of sarcoma. • Targeting TJP1 attenuates cell-cell aggregation and anchorage-independent growth. • Targeting TJP1 is beneficial in anti-cancer therapy in LMS.

Existing CNN-based super resolution methods have low emphasis on high-frequency features, resulting in poor performance for contours and textures. To solve this problem, this paper proposes single image super resolution using an attention mechanism that emphasizes high-frequency features and a feature extraction process with different depths. In order to emphasize the high-frequency features of the channel and space, it is composed of CSBlock that combines channel attention and spatial attention. Attention block using 10 CSBlocks was used for high-frequency feature extraction. In order to extract various features with different degrees of feature emphasis from insufficient low-resolution features, features were extracted from structures connected with different numbers of attention blocks. The extracted features were expanded through sub-pixel convolution to create super resolution images, and learning was performed through L1 loss. Compared to the existing deep learning method, it showed improved results in several high-frequency features such as small object outlines and line patterns. In PSNR and SSIM, it showed about 11% to 26% improvement over the existing Bicubic interpolation and about 1 to 2% improvement over VDSR and EDSR.

Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models.To recapitulate human CRCs, we generated Villin-Cre;Smad4Twenty-week-old Villin-Cre;Smad4Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/β-catenin pathway.

Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor (ER)-positive breast cancer by analyzing mutations and copy number variants (CNV), and by applying expression profiling. The whole exome and transcriptome of 47 Korean young breast cancer (KYBR) patients (age

본 연구의 목적은 노인성 우울, 노인성 스트레스와 인지기능과의 연관성을 확인하는 것이다. 구체적으로 치매를 유발 원인에 따라 알츠하이머성 치매와 혈관성 치매의 두 그룹으로 분류하고 각 그룹의 인지장애 및 노인성 우울, 노인성 스트레스의 정도와 특성의 차이를 확인하고 상호간의 연관성을 비교하고자 한다. 인지기능의 변수는 한국형 간이정신상태검사, 치매임상평가척도, 이마엽 기능검사, 한국형 도구적 일상생활능력 평가를 사용하였고, 노인성 우울변수는 노인우울척도(GDS), 노인성 스트레스변수는 노인스트레스척도(GSS)를 사용하였다. 통계적 방법은 알츠하이머성 치매환자 80명, 혈관성 치매환자 80명, 통제를 위한 정상군 80명을 설정하여 기술 통계량, Kruskall-Wallis, 상관분석, 다중회귀분석으로 통계적으로 유의한 차이 및 연관성을 확인하였다. 알츠하이머성 치매군에서는 GDS, GSS와 대체적으로 인지기능 변수들과의 상관관계는 확인하였다. 특히 GDS는 남성에서만 인지기능 변수들과 상관관계가 있고, 인지기능 변수들과의 인과관계도 확인되었다. 또한 GSS와 GDS와의 인과관계를 확인하여 GSS가 GDS의 원인이 된다는 유의성을 확인하였다. 결론적으로 GDS는 알츠하이머성 치매군에서 인지기능 변수와의 상관관계와 직접적인 인과관계를 확인하였고, GSS는 직접적인 상관관계보다 GDS를 유발하여 인지기능 장애와의 간접적인 인과관계를 확인할 수 있었다.

Recent advances in metal additive manufacturing (AM) have provided new opportunities for the design of prototypes of metal-based products and personalization of products for the fourth industrial revolution. Although metal AM, which enables fabrication of varied and sophisticated objects, is in the spotlight as a next-generation printing method, environmental issues arising during the printing process need to be addressed before it can be commercialized. Here, we demonstrate a novel mechanism for binder jetting three-dimensional (3D) printing of metals that is based on chelation triggered by an eco-friendly binding agent. Sodium salts of fruit acid chelators are used to form stable metal-chelate bridges between metal particles, which enable elaborate metal 3D printing. The strength of the 3D-printed object is improved by post-treatment, through a reduction in the porosity between the metal particles. Finally, the compatibility of the novel printing mechanism with a variety of metals is demonstrated via successful 3D printing of objects of various shapes using various metal powders. The proposed mechanism for metal 3D printing is expected to open up new avenues for the development of domestic-scale desktop 3D printing of metals.

Hydraulic structures have a significant impact on riverine environment, leading to changes in stream&ndash, aquifer interactions. In South Korea, 16 weirs were constructed in four major rivers, in 2012, to secure sufficient water resources, and some weirs operated periodically for natural ecosystem recovery from 2017. The changed groundwater flow system due to weir operation affected the groundwater level and quality, which also affected groundwater use. In this study, we analyzed the changes in the groundwater flow system near the Geum River during the Baekje weir operation using Visual MODFLOW Classic. Groundwater data from 34 observational wells were evaluated to analyze the impact of weir operation on stream&ndash, aquifer interactions. Accordingly, the groundwater discharge rates increased from 0.23 to 0.45 cm/day following the decrease in river levels owing to weir opening, while the hydrological condition changed from gaining to losing streams following weir closure. The variation in groundwater flow affected the groundwater quality during weir operation, changing the groundwater temperature and electrical conductivity (EC). Our results suggest that stream&ndash, aquifer interactions are significantly affected by weir operation, consequently, these repeated phenomena could influence the groundwater quality and groundwater use.

Alternative splicing (AS) regulates biological processes governing phenotypes and diseases. Differential AS (DAS) gene test methods have been developed to investigate important exonic expression from high-throughput datasets. However, the DAS events extracted using statistical tests are insufficient to delineate relevant biological processes. In this study, we developed a novel application, Alternative Splicing Encyclopedia: Functional Interaction (ASpediaFI), to systemically identify DAS events and co-regulated genes and pathways. ASpediaFI establishes a heterogeneous interaction network of genes and their feature nodes (i.e., AS events and pathways) connected by co-expression or pathway gene set knowledge. Next, ASpediaFI explores the interaction network using the random walk with restart algorithm and interrogates the proximity from a query gene set. Finally, ASpediaFI extracts significant AS events, genes, and pathways. To evaluate the performance of our method, we simulated RNA sequencing (RNA-seq) datasets to consider various conditions of sequencing depth and sample size. The performance was compared with that of other methods. Additionally, we analyzed three public datasets of cancer patients or cell lines to evaluate how well ASpediaFI detects biologically relevant candidates. ASpediaFI exhibits strong performance in both simulated and public datasets. Our integrative approach reveals that DAS events that recognize a global co-expression network and relevant pathways determine the functional importance of spliced genes in the subnetwork. ASpediaFI is publicly available at https://bioconductor.org/packages/ASpediaFI.

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein’s biological functions in dopamine-based neurogenesis.

Motivation High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. Results Here we introduce ‘soft windowing’, a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype–phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. Availability and implementation The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. Supplementary information Supplementary data are available at Bioinformatics online.

Background Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. Results The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. Conclusions This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy. Electronic supplementary material The online version of this article (10.1186/s12881-018-0722-6) contains supplementary material, which is available to authorized users.

We conducted an RNA sequencing study to identify novel gene fusions in 80 discovery dataset tumors collected from young patients with diffuse gastric cancer (DGC). Twenty-five in-frame fusions are associated with DGC, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) are recurrent in 384 DGCs based on RT-PCR. All three fusions contain a RhoGAP domain in their 3’ partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without. Ectopic expression of CLDN18-ARHGAP26 promotes the migration and invasion capacities of DGC cells. Parallel targeted RNA sequencing analysis additionally identifies TACC2-PPAPDC1A as a recurrent and poor prognostic in-frame fusion. Overall, PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly define the aggressive subset (7.5%) of DGCs, and their prognostic impact is greater than, and independent of, chromosomal instability and CDH1 mutations. Our study may provide novel genomic insights guiding future strategies for managing DGCs., Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

Background & Aims WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. Methods Three spasmolytic polypeptide–expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777–treated gastric corpus specimens. Results Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. Conclusions WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Alternative splicing confers the human genome complexity by increasing the diversity of expressed mRNAs. Hundreds or thousands of splicing regions have been identified through differential alternative splicing analysis of high-throughput datasets. However, it is hard to explain the functional impact of each splicing event. Protein domain formation and nonsense-mediated decay are considered the main functional features of splicing. However, other functional features such as miRNA target sites, phosphorylation sites and single-nucleotide variations are directly affected by alternative splicing and affect downstream function. Hence, we established ASpedia: a comprehensive database for human alternative splicing annotation, which encompasses a range of functions, from genomic annotation to isoform-specific function (ASpedia, http://combio.snu.ac.kr/aspedia). The database provides three features: (i) genomic annotation extracted from DNA, RNA and proteins; (ii) transcription and regulation elements analyzed from next-generation sequencing datasets; and (iii) isoform-specific functions collected from known and published datasets. The ASpedia web application includes three components: an annotation database, a retrieval system and a browser specialized in the identification of human alternative splicing events. The retrieval system supports multiple AS event searches resulting from high-throughput analysis and the AS browser comprises genome tracks. Thus, ASpedia facilitates the systemic annotation of the functional impacts of multiple AS events.

The development and application of all-solid-state batteries with a fast lithium-ionic conductor are hampered by structural instability and rigid stoichiometry restrictions. Here, we present a family of lithium thiophosphate prototypes with a novel principle, controlling sulfur deficiencies with the addition of nickel sulfide-based additives, for fast lithium-ion conduction and distinct electrochemical stability under the extended material constituent. Well-controlled sulfur deficiency of the Li3PS4 framework accompanied by nickel sulfide additive offers the notable increase of lithium-ion conductivity (2 × 10–3 S cm–1 at 25 °C) and high electrochemical stability (up to 10 V vs Li/Li+) in a wide composition range. We further confirm the potential application of our fast composite lithium-ion conductor as an electrolyte for the all-solid-state battery with 117 mAh g–1 capacity delivery and stable cycle life.

21세기 인재상의 변화가 교육의 변화를 요구하면서 세계적으로 역량 중심 교육 개혁이 진행되고 있다. 우리나라도 2015 개정 교육과정에 핵심 역량을 제시하고 이를 토대로 교육과정을 재구성하고 학생 중심으로 수업을 진행하며, 수업과 연계된 과정 중심 평가가 일관되게 이루어질 것을 요구하고 있다. 그러나 조사 결과, 현장에서는 교육과정, 수업, 평가의 연계에 대한 인식과 실행이 적극적으로 이루어지지 못하고 있으며, 특히 대학 입시 부담이 큰 고등학교로 갈수록 이러한 현상은 심화되고 있는 것으로 나타났다. 이에 본 연구는 고등학교 현장에서 역량기반 교육과정-수업-평가의 연계를 통한 역량 중심 교육의 성공적 실현을 위하여 고등학교 현장의 교사들의 의견을 토대로 교육과정과 수업, 평가의 연계가 실현되지 못하는 원인을 파악하고 이를 해결할 수 있는 방안을 제시하고자 하였다. 이를 위하여 서울, 경기도 소재 고등학교 교사들을 대상으로 심층면담을 진행하여 면담 결과를 근거이론을 활용하여 분석한 결과, 고등학교 현장에서의 역량기반 교육과정-수업-평가의 연계를 현실화 할 수 있는 방안은 역량을 중심으로 하는 대학입시제도와 사회구조로의 전환, 교육 주체 간 소통과 공유를 통한 공감대 형성, 교육과정 문해력 신장 노력을 독려하고, 교사들의 실천 의지 형성과 교사의 자발적 참여를 유도하는 행정적 지원, 민주적 리더십을 토대로 한 학교장의 지원, 교육철학에 대한 성찰을 토대로 한 교육 본질의 회복을 위한 노력이었다.

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.

Groundwater samples were collected from 3818 wells used for the community groundwater system (CGS) in the remote rural areas of South Korea and analyzed to determine radon concentrations. Radon concentrations varied with rock type, ranging from 0.1 to 2393.5 Bq/L with an average of 86.6 Bq/L and a median of 46.4 Bq/L. Among 10 geological units, the median CGS radon concentration was highest (59.6-103.0 Bq/L) in granite, and lower in sedimentary rocks (16.9-21.1 Bq/L) and porous volcanic rocks (17.6 Bq/L), respectively. Of the 3818 samples, 26.1% exceeded the World Health Organization (WHO) radon level limit of 100 Bq/L. The application of the natural radon reduction rate (26.5%) recently suggested by Yun et al. Applied Radiation and Isotopes, 126(1), 23-25 (2017) to the CGS water tank appeared to decrease exceedance of the WHO radon level limit to 20.2%. Because of the high radon concentrations in CGS groundwater in South Korea, the establishment of a radon level limit for drinking water is strongly recommended to ensure the health and safety of the people using CGS water.

Prior studies have demonstrated the utility of microRNA assays for predicting some cancer tissue origins, but these assays need to be further optimized for predicting the tissue origins of adenocarcinomas of the liver. We performed microRNA profiling on 195 frozen primary tumor samples using 14 types of tumors that were either adenocarcinomas or differentiated from adenocarcinomas. The 1-nearest neighbor method predicted tissue-of-origin in 33 samples of a test set, with an accuracy of 93.9% at feature selection p values ranging from 10−4 to 10−10. According to binary decision tree analyses, the overexpression of miR-30a and the underexpression of miR-200 family members (miR-200c and miR-141) differentiated intrahepatic cholangiocarcinomas from extrahepatic adenocarcinomas. When binary decision tree analyses were performed using the test set, the prediction accuracy was 84.8%. The overexpression of miR-30a and the reduced expressions of miR-200c, miR-141, and miR-425 could distinguish intrahepatic cholangiocarcinomas from liver metastases from the gastrointestinal tract.

The recharge fractions of injection water in combined abstraction-injection wells (AIW) were determined using continuous radon monitoring and radon mass balance model. The recharge system consists of three combined abstraction-injection wells, an observation well, a collection tank, an injection tank, and tubing for heating and transferring used groundwater. Groundwater was abstracted from an AIW and sprayed on the water-curtain heating facility and then the used groundwater was injected into the same AIW well by the recharge system. Radon concentrations of fresh groundwater in the AIWs and of used groundwater in the injection tank were measured continuously using a continuous radon monitoring system. Radon concentrations of fresh groundwater in the AIWs and used groundwater in the injection tank were in the ranges of 10,830–13,530 Bq/m3 and 1500–5600 Bq/m3, respectively. A simple radon mass balance model was developed to estimate the recharge fraction of used groundwater in the AIWs. The recharge fraction in the 3 AIWs was in the range of 0.595–0.798. The time series recharge fraction could be obtained using the continuous radon monitoring system with a simple radon mass balance model. The results revealed that the radon mass balance model using continuous radon monitoring was effective for determining the time series recharge fractions in AIWs as well as for characterizing the recharge system.

Lipids are important signaling molecules regulating biological processes under normal and diseased conditions. Although p53 mutation is well-known for causing cancer, the relationship between p53-related tumorigenesis and altered lipid profile is unclear. We profiled differences in lipid expressions in liver, lung, and kidney in p53 knockout (KO) mice by high-speed quantitative analysis of 320 lipids (399 species identified) using nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUPLC-MS/MS). Lung tissues were most severely affected by the lack of p53 gene, as shown by significant reduction (24-44%, P0.05) in total phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG), and significant increases (30-50%) in phosphatidylserine (PS), phosphatidylinositol (PI), and monohexosylceramide (MHC). MHC levels increased in all tissues. Dihexosylceramide (DHC) level decreased only in kidney tissue. Most PI, PS, and phosphatidic acid (PA) species showing significant increases contained a saturated acyl chain (18:0) in lung and liver tissues. Neutral glycerolipids (16:0/22:0-DG and most TGs with saturated and monounsaturated acyl chains) decreased 2-4-fold in the liver tissue. Our results suggest that the lack of p53 and altered lipid profiles are closely related, but as their changes vary from one tissue to another, the lipid alterations are tissue-specific.

The genetic algorithm (GA), one of the artificial intelligence (AI), is developed based on Darwin"s theory of evolution, i.e., the mating of randomly selected objects. If more optimal solution is generated, then it is better to repeat the process of setting the optimum value. In this paper, the method of background music using the genetic algorithm is exploited when the computer game is executed each time. As a result, it has created several music that can be used in the actual game, and it could be confirmed that the other music that is created is different music when performed each time.

We use first-principles calculation to investigate the influence of lattice strain on the oxygen vacancy and the migration energies in La 1- x SrCoO 3- δ via a realistic approach using the Poisson's ratio. In the calculation of the vacancy formation energy, it was found that the oxygen sites in the major axis are favorable for achieving vacancy under tensile conditions, while those in the minor axis are in favor of vacancy formation under compressive conditions. The migration energy calculations for oxygen vacancy are also carried out and this reveals interesting strain dependence, higher activation energy when compressive strain is applied in the lateral direction.

Objective : This study performed to evaluate that duration of acne scars effects on Qualitative Global Acne Scarring Grading System(QGASC) grade changing and treatment dur ation. Also this study performed to evaluate the relationship between dysmenorrhea and acne scars, and the effec ts of each treatment on treatment duration and Korean Acne Grading System(KAGS) and QGASC grade. Methods : 95 patients with acne scars were understood by medical reco rds and case photos, and we evaluated pre and post acne scar grade based on KAGS and QGASC. We analyzed data by SPSS 22 for windows program, and figured out the relation between duration of acne and QGASC grade and treatment duration by Spearman correlation analysis, and performed Mann-Whitney U-test to figu re out the relation between dysmenorrhea and QGASC grade. We performed Wilcoxon test to evaluate that treatm ent of acne scars effects on KAGS grade and QGASC grade, and performed Kruskal-Wallis test to figure out th e difference of each treatment which effects on KAGS grade and QGASC grade, and performed Post-hoc analysis to figure out the group comparison. Results & Conclusions : QGASC grade depending on duration of acne was statistically s ignificance. Subcision and Microneedle Therapy System(MTS) and pharmacopuncture were signi ficantly improved acne scars. Other treatments were significantly more effective than subcision and pharmacopu ncture combined treatment. Treatment duration of Subcision and MTS combined treatment was significantly most sho rtest than other treatment.Key words : Acne scars; Subcision; MTS; Pharmacopuncture

Studying groundwater inflow and quantifying its flux into aquatic systems remain challenging because of geological and topographical heterogeneities. In this study, we measured the 222Rn activities in the surface water and porewater of a shallow wetland, the Baekseok Reservoir Wetland, to investigate the groundwater flow system and quantify the groundwater inflow rate. Three field campaigns were carried out in April 2018, September 2018, and February 2019 to determine the spatial and temporal variations in the 222Rn activity. The 222Rn activities were significantly higher along the western boundary of the wetland than the eastern boundary, suggesting a significant difference in the groundwater inflow rate, which reflects different hydrological characteristics on the two boundaries of the wetland. The results of hydrogeological investigations (electrical resistivity survey and monitoring of groundwater and surface water levels) and microbiological analyses were consistent with the 222Rn distribution results, supporting our hypothesis that the groundwater inflow qualitatively and quantitatively exhibits a spatial difference. Based on the mass balances of water and 222Rn under a steady-state condition, the groundwater inflow rates were estimated to be 3.2 × 102, 1.7 × 103, and 7.6 × 102 m3 day−1 in April, September, and February, respectively. The highest groundwater inflow rate in September may be due to the relatively high hydraulic gradient resulting from intense rainfall events. The water residence time of the wetland estimated from the 222Rn mass balance results was approximately one month regardless of the seasons. In addition, the groundwater-derived dissolved silica flux accounted for ~60% of the total dissolved silica input flux of the wetland, highlighting the importance of groundwater-derived dissolved silica. Our multidisciplinary approach to identify and quantify groundwater inflow has important implications in determining groundwater sources in aquatic systems and the behaviors of other substances, such as dissolved nutrients.

The role of Ahnak in obesity has been reported previously. Loss of Ahnak leads to decreased Bmp4/Smad1 signaling, resulting in the downregulation of adipocyte differentiation. However, the biological significance of Ahnak remains largely unknown. In this study, we demonstrate that Ahnak-mediated impaired adipogenesis results in decreased Bmpr1α transcriptional expression. To confirm this, Ahnak siRNA was used to knock-down Ahnak in C3H10T1/2 and primary stromal vascular fraction cells. Ahnak siRNA transfected cells showed suppression of Bmpr1α expression and decreased BMP4/ Bmpr1α signaling. The differential adipogenesis was further confirmed by knock-down of Bmpr1α in C3H10T1/2 cells, which resulted in reduced adipogenesis. Moreover, stable Ahnak knock-out C3H10T1/2 cells stably transfected with Ahnak CRISPR/Cas9 plasmid suppressed expression of Bmpr1α and prevented differentiation into adipocytes. Furthermore, we developed immortalized pre-adipocytes from wild-type or Ahnak Knock-out mice’s stromal vascular fraction (SVF) to confirm the function of Ahnak in pre-adipocyte transition. Immortalized Ahnak knock-out SVF cells showed lower level of Bmpr1α expression, evidence by their impaired BMP4/Bmpr1α signaling. Upon adipogenic induction, immortalized Ahnak knock-out SVF cells exhibited a marked decrease in adipocyte differentiation compared with immortalized wild-type pre-adipocytes. Furthermore, over-expression of Bmpr1α restored the adipogenic activity of Ahnak knock-out C3H10T1/2 cells and immortalized Ahnak knock-out SVF cells. Our data reveal the missing link in Ahnak-mediated adipose tissue remodeling and suggest that precise regulation of Ahnak in adipose tissue might have a therapeutic advantage for metabolic disease treatment.

The seasonal variation of the 7Be activities in air was monitored by a continuous sampling with a high volume air dust sampler. And also, 7Be and 3H activities in precipitation were determined. The activity level of 7Be in air was ranged from 1.94 to 47.2 Bq/m3. And 7Be in the precipitation was separated using cation exchange resin and the monthly average activity level was ranged from 0.29 to 4.77 Bq/L. 3H was analyzed using electrolytic enrichment method and activity ranged from 0.27 to 2.22 Bq/L.

Radon and stable nuclides were used as a tracer of groundwater/surface water interaction study in a artificial groundwater recharge system near Nakdong river in Korea. The 222Rn concentration at the observation well groundwater was decreased. The activity variation of each monitoring wells during short and long term experiment were 6.5–12.4 Bq/L at OBS-1, 3.8–6.8 Bq/L at OBS-2, 30.9–55.9 Bq/L at OBS-3, 5.9–25.5 Bq/L at OBS-4, 22.1–34.6 Bq/L at OBS-5 and 7.1–28.3 Bq/L at OBS-6. The 222Rn concentration of OBS-1 and 5 were decrease about 35 % but OBS-6 was increased.

Background The beach chair position (BCP) is associated with hypotension that may lead to cerebral ischemia. Arginine vasopressin (AVP), a potent vasoconstrictor, has been shown to prevent hypotension in BCP. It also improves cerebral oxygenation in different animal models. The present study examined the effect of escalating doses of AVP on systemic hemodynamics and cerebral oxygenation during surgery in BCP under general anesthesia. Methods Sixty patients undergoing arthroscopic shoulder surgery in BCP under general anesthesia were randomly allocated to receive either saline (control, n = 15) or three different doses of AVP (0.025, 0.05, or 0.075 U/kg; n = 15 each) 2 minutes before BCP. Mean arterial pressure (MAP), heart rate (HR), regional cerebral oxygen saturation (SctO2), and jugular venous oxygen saturation (SjvO2) were measured after induction of anesthesia and before (presitting in supine position) and after BCP. Results AVP per se given before BCP increased MAP, and decreased SjvO2, SctO2, and HR in all patients (P < 0.05 for all). BCP decreased MAP, the magnitude of which and hence the incidence of hypotension was decreased by AVP in a dose-dependent manner. While in BCP, every dose of AVP reduced the HR and SctO2. Accordingly, it increased the incidence of cerebral desaturation (> 20% SctO2 decrease from the baseline value) with no differences in SjvO2 and the incidence of SjvO2 < 50% or SjvO2 < 40% among the groups. Conclusions AVP ameliorates hypotension associated with BCP in a dose-dependent manner in patients undergoing shoulder surgery under general anesthesia. However, AVP may have negative effects on SctO2 before and after BCP and on SjvO2 before BCP.

Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported. Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured. Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats. Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.