• Asian-Australasian Journal of Animal Sciences
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• v.32 no.2
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• pp.290-296
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• 2019

Objective: Pigs share many physiological, anatomical and genomic similarities with humans, which make them suitable models for biomedical researches. Understanding the genetic status of Yucatan miniature pigs (YMPs) and their association with human diseases will help to assess their potential as biomedical model animals. This study was performed to identify non-synonymous single nucleotide polymorphisms (nsSNPs) in selective sweep regions of the genome of YMPs and present the genetic nsSNP distributions that are potentially associated with disease occurrence in humans. Methods: nsSNPs in whole genome resequencing data from 12 YMPs were identified and annotated to predict their possible effects on protein function. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping v2 analyses were used, and gene ontology (GO) network and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Results: The results showed that 8,462 genes, encompassing 72,067 nsSNPs were identified, and 118 nsSNPs in 46 genes were predicted as deleterious. GO network analysis classified 13 genes into 5 GO terms (p<0.05) that were associated with kidney development and metabolic processes. Seven genes encompassing nsSNPs were classified into the term associated with Alzheimer's disease by referencing the genetic association database. The KEGG pathway analysis identified only one significantly enriched pathway (p<0.05), hsa04080: Neuroactive ligand-receptor interaction, among the transcripts. Conclusion: The number of deleterious nsSNPs in YMPs was identified and then these variants-containing genes in YMPs data were adopted as the putative human diseases-related genes. The results revealed that many genes encompassing nsSNPs in YMPs were related to the various human genes which are potentially associated with kidney development and metabolic processes as well as human disease occurrence.

• Journal of Korean Society of Industrial and Systems Engineering
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• v.44 no.4
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• pp.32-42
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• 2021

The printing process can have to print various colors with a limited capacity of printing facility such as ink containers that are needed cleaning to change color. In each container, cleaning time exists to assign corresponding inks, and it is considered as the setup cost required to reduce the increasing productivity. The existing manual method, which is based on the worker's experience or intuition, is difficult to respond to the diversification of color requirements, mathematical modeling and algorithms are suggested for efficient scheduling. In this study, we propose a new type of scheduling problem for the printing process. First, we suggest a mathematical model that optimizes the color assignment and scheduling. Although the suggested model guarantees global optimality, it needs a lot of computational time to solve. Thus, we decompose the original problem into sequencing orders and allocating ink problems. An approximate function is used to compute the job scheduling, and local search heuristic based on 2-opt algorithm is suggested for reducing computational time. In order to verify the effectiveness of our method, we compared the algorithms' performance. The results show that the suggested decomposition structure can find acceptable solutions within a reasonable time. Also, we present schematized results for field application.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.464-472
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• 2022

Background: Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain. Methods: Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aβ) accumulation demonstrated through Aβ 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test. Results: KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aβ 42/40 ratio (p < 0.01) indicating reduced Aβ accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%). Conclusions: KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.75-84
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• 2023

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, βmyosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 ㎍/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A₂ (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy. Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ

• Development and Reproduction
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• v.27 no.4
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• pp.205-211
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• 2023

INTS14/VWA9, a component of the integrator complex subunits, plays a pivotal role in regulating the fate of numerous nascent RNAs transcribed by RNA polymerase II, particularly in the biogenesis of small nuclear RNAs and enhancer RNAs. Despite its significance, a comprehensive mutation model for developmental research has been lacking. To address this gap, we aimed to investigate the expression patterns of INTS14 during zebrafish embryonic development. We generated ints14 mutant strains using the CRISPR/Cas9 system. We validated the gRNA activity by co-injecting Cas9 protein and a single guide RNA into fertilized zebrafish eggs, subsequently confirming the presence of a 6- or 9-bp deletion in the ints14 gene. In addition, we examined the two mutant alleles through PCR analysis, T7E1 assay, TA-cloning, and sequencing. For the first time, we used the CRISPR/Cas9 system to create a model in which some sequences of the ints14 gene were removed. This breakthrough opens new avenues for in-depth exploration of the role of ints14 in animal diseases. The mutant strains generated in this study can provide a valuable resource for further investigations into the specific consequences of ints14 gene deletion during zebrafish development. This research establishes a foundation for future studies exploring the molecular mechanisms underlying the functions of ints14, its interactions with other genes or proteins, and its broader implications for biological processes.

• The Korean Journal of Malacology
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• v.32 no.3
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• pp.185-188
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• 2016

PANM-DB (version 1.0) was constructed as a web-based interface for the analysis and annotation of Next-Generation Sequencing (NGS) data of Mollusca, Arthropoda, and Nematoda. The database collected the sequences of Protostomes (Mollusca, Arthropoda, and Nematoda) from the NCBI Taxonomy Browser, and the same were compiled in a multi-FASTA format and stored using the formatdb program. This improved the processing of the RNA-seq sequences in terms of speed and hit percentage. PANM-DB has been successfully used for the transcriptome annotation of butterfly, land snail, and other commercial mollusca. We have improved the database by updating the same with new sequences and version 2.0 contains a total of 7,571,246 protein sequences (two times more as compared to version 1.0). Furthermore, the updated version contains the Cephalopoda database. The constructed web interface is available that independently analyses following these updates that is an improvement of the mollusks BLAST server. The updated version of PANM-DB will be helpful for the analysis of the NGS based sequencing data of non-model species, especially Mollusca, Arthropoda, Nematoda.

• BMB Reports
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• v.51 no.11
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.73-73
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• 2018

Bacterial leaf blight(BLB), caused by X. oryzae pv. oryzae(Xoo), is one of the most destructive diseases of rice due to its high epidemic potential. Understanding BLB resistance at a genetic level is important to further improve the rice breeding that provides one of the best approaches to control BLB disease. In the present investigation, a collection of 192 accessions was used in the genome-wide association study (GWAS) for BLB resistance loci against four Korean races of Xoo that were represented by the prevailing BLB isolates under Xoo differential system. A total of 192 accessions of rice germplasm were selected on the basis of the bioassay using four isolated races of Xoo such as K1, K2, K3 and K3a. The selected accessions was used to prepare 384-plex genotyping by sequencing (GBS) libraries and Illumina HiSeq 2000 paired- end read was used for GBS sequencing. GWAS was conducted using T ASSEL 5.0. The T ASSEL program uses a mixed linear model (MLM). T he results of the bioassay using a selected set of 192 accessions showed that a large number of accessions (93.75%) were resistant to K1 race, while the least number of accessions (34.37%) resisted K3a race. For races K2 and K3, the resistant germplasm proportion remained between 66.67 to 70.83%. T he genotypic data produced SNP matrix for a total of 293,379 SNPs. After imputation the missing data was removed, which exhibited 34,724 SNPs for association analysis. GWAS results showed strong signals of association at a threshold of [-log10(P-value)] more than5 (K1 and K2) and more than4 (K3 and K3a) for nine of the 39 SNPs, which are plausible candidate loci of resistance genes. T hese SNP loci were positioned on rice chromosome 2, 9, and 11 for K1 and K2 races, whereas on chromosome 4, 6, 11, and 12 for K3 and K3a races. The significant loci detected have also been illustrated, NBS-LRR type disease resistance protein, SNARE domain containing protein, Histone deacetylase 19, NADP-dependent oxidoreductase, and other expressed and unknown proteins. Our results provide a better understanding of the distribution of genetic variation of BLB resistance to Korean pathogen races and breeding of resistant rice.

• Journal of Life Science
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• v.27 no.6
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• pp.617-622
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• 2017

In this study, we sought to develop an effective cloning system by which human cytochrome $b_5$ (cyt $b_5$) is introduced and expressed in zebrafish. First, the 414 bp human cyt $b_5$ gene was amplified from RNA extracts of HeLa cells using RT-PCR, and the amplicon was subsequently sequenced to confirm that it was intact. Next, cyt $b_5$ was cloned into the pEGFP-N3 vector, which also encodes a fluorescent gene. One-cell stage zebrafish embryos were microinjected with the recombinant vector containing the cyt $b_5$ gene. Fluorescence microscopy confirmed high expression of the fluorescent gene in the injected fry compared to the non-fluorescent control fry. Finally, we extracted RNA from the injected fry and performed RT-PCR to determine whether the human cyt $b_5$ gene is expressed in the transgenic zebrafish. Sequencing analysis further confirmed that the cloned human cyt $b_5$ gene was intact. The transgenic zebrafish model produced in this study will be a useful tool to study therapeutic approaches to cure various diseases related to the deficiency of functional human cyt $b_5$ as well as tools for cloning useful genes in fish.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.