• Genomics & Informatics
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• v.21 no.1
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• pp.7.1-7.11
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• 2023

The gram-positive bacterium Listeria monocytogenes is an important foodborne intracellular pathogen that is widespread in the environment. The functions of hypothetical proteins (HP) from various pathogenic bacteria have been successfully annotated using a variety of bioinformatics strategies. In this study, a HP Imo0888 (NP_464414.1) from the Listeria monocytogenes EGD-e strain was annotated using several bioinformatics tools. Various techniques, including CELLO, PSORTb, and SOSUIGramN, identified the candidate protein as cytoplasmic. Domain and motif analysis revealed that the target protein is a PemK/MazF-like toxin protein of the type II toxin-antitoxin system (TAS) which was consistent with BLASTp analysis. Through secondary structure analysis, we found the random coil to be the most frequent. The Alpha Fold 2 Protein Structure Prediction Database was used to determine the three-dimensional (3D) structure of the HP using the template structure of a type II TAS PemK/MazF family toxin protein (DB ID_AFDB: A0A4B9HQB9) with 99.1% sequence identity. Various quality evaluation tools, such as PROCHECK, ERRAT, Verify 3D, and QMEAN were used to validate the 3D structure. Following the YASARA energy minimization method, the target protein's 3D structure became more stable. The active site of the developed 3D structure was determined by the CASTp server. Most pathogens that harbor TAS create a crucial risk to human health. Our aim to annotate the HP Imo088 found in Listeria could offer a chance to understand bacterial pathogenicity and identify a number of potential targets for drug development.

• Genomics & Informatics
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• v.19 no.1
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• pp.3.1-3.12
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• 2021

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer-associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type-specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer-associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

• Genomics & Informatics
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• v.21 no.1
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• pp.3.1-3.10
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• 2023

Characterization as well as prediction of the secondary and tertiary structure of hypothetical proteins from their amino acid sequences uploaded in databases by in silico approach are the critical issues in computational biology. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), which is responsible for pneumonia alike diseases, possesses a wide range of proteins of which many are still uncharacterized. The current study was conducted to reveal the physicochemical characteristics and structures of an uncharacterized protein Q6S8D9_SARS of SARS-CoV. Following the common flowchart of characterizing a hypothetical protein, several sophisticated computerized tools e.g., ExPASy Protparam, CD Search, SOPMA, PSIPRED, HHpred, etc. were employed to discover the functions and structures of Q6S8D9_SARS. After delineating the secondary and tertiary structures of the protein, some quality evaluating tools e.g., PROCHECK, ProSA-web etc. were performed to assess the structures and later the active site was identified also by CASTp v.3.0. The protein contains more negatively charged residues than positively charged residues and a high aliphatic index value which make the protein more stable. The 2D and 3D structures modeled by several bioinformatics tools ensured that the proteins had domain in it which indicated it was functional protein having the ability to trouble host antiviral inflammatory cytokine and interferon production pathways. Moreover, active site was found in the protein where ligand could bind. The study was aimed to unveil the features and structures of an uncharacterized protein of SARS-CoV which can be a therapeutic target for development of vaccines against the virus. Further research are needed to accomplish the task.

• Journal of Microbiology and Biotechnology
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• v.19 no.3
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• pp.271-276
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• 2009

Functional gene studies in the cultivated white button mushroom Agaricus bisporus have been constrained by the absence of effective gene-silencing tools. Using two endogenous genes from A. bisporus, we have tested the utility of dsRNA hairpin constructs to mediate downregulation of specific genes. Hairpin constructs for genes encoding orotidine 5'-monophosphate decarboxylase (URA3) and carboxin resistance (CBX) were introduced into A. bisporus using Agrobacteriummediated transfection. Although predicted changes in phenotype were not observed in vitro, quantitative-PCR analyses indicated unambiguously that transcripts in several transformants were substantially reduced compared with the non-transformed controls. Interestingly, some hairpin transformants exhibited increased transcription of target genes. Our observations show that hairpin transgenic sequences can mediate downregulation of A. bisporus endogenous genes and that the technology has the potential to expedite functional genomics of the mushroom.

• Genomics & Informatics
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• v.18 no.3
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• pp.27.1-27.12
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• 2020

The prevalence of early-onset type 2 diabetes (EOT2D) is increasing in Asian countries. Genome-wide association studies performed in European and various other populations have identified associations of numerous variants with type 2 diabetes in adults. However, the genetic component of EOT2D which is still unexplored could have similarities with late-onset type 2 diabetes. Here in the present study we aim to identify the association of variants with EOT2D in South Indian population. Twenty-five variants from 18 gene loci were genotyped in 1,188 EOT2D and 1,183 normal glucose tolerant subjects using the MassARRAY technology. We confirm the association of the HHEX variant rs1111875 with EOT2D in this South Indian population and also the association of CDKN2A/2B (rs7020996) and TCF7L2 (rs4506565) with EOT2D. Logistic regression analyses of the TCF7L2 variant rs4506565(A/T), showed that the heterozygous and homozygous carriers for allele 'T' have odds ratios of 1.47 (95% confidence interval [CI], 1.17 to 1.83; p = 0.001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele 'C' have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele 'C' were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.334-339
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• 2007

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

• Genomics & Informatics
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• v.6 no.1
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• pp.50-53
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• 2008

We have released five Java Application Programming Interface (API) packages for viewing three-dimensional structures of proteins from the Protein Data Bank. To this end, the user interface of an earlier version has been refactored in an object-oriented fashion, in which refactoring is the process of changing a software system to improve its internal structure, without altering the external behavior. Various GUI design and features have been provided conveniently thanks to the Model-View-Control (MVC) model, which is an architectural pattern used in software engineering. Availability: The source code and API specification can be downloaded from https://sourceforge.net/projects/j3dpsv/.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.55-59
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• 2021

West syndrome (WS) presenting with infantile spasms, developmental delay, and hypsarrhythmia has genetic etiology in some patients. Movement disorders or visual impairment that share genetic underpinnings with infantile spasms can provide diagnostic clues for specific genetic mutations. Mutations of the GRIN1 gene encoding the glutamate receptor inotropic N-methyl-D-aspartate subunit can result in WS with hyperkinetic movements, cortical visual impairment, autistic features, and bilateral polymicrogyria. An 11-month-old boy with WS showed hyperkinetic movements and visual impairment. Brain magnetic resonance imaging and metabolic investigations revealed no abnormalities. Whole-exome sequencing revealed a novel likely pathogenic variant (c.1561_1563del; p.Asn521del) of GRIN1 (NM_007327.3). The proband was treated with vigabatrin and became seizure-free within one week. Notably, the cortical blindness improved within 3 months and the hyperkinetic movements resolved one year after the proband became seizure-free. To the best of our knowledge, this is the first report of GRIN1 encephalopathy in Koreans.

• Genomics & Informatics
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• v.18 no.3
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• pp.32.1-32.7
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• 2020

The mitochondrial genome of a species is an essential resource for its effective conservation and phylogenetic studies. In this article, we present sequencing and characterization of the complete mitochondrial genome of a threatened labeonine fish, Cirrhinus reba collected from Khulna region of Bangladesh. The complete mitochondrial genome was 16,597 bp in size, which formed a circular double-stranded DNA molecule containing a total of 37 mitochondrial genes (13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes) with two non-coding regions, an origin of light strand replication (OL) and a displacement loop (D-loop), similar structure with other fishes of Teleostei. The phylogenetic tree demonstrated its close relationship with labeonine fishes. The complete mitogenome of Cirrhinus reba (GenBank no. MN862482) showed 99.96% identity to another haplotype of Cirrhinus reba (AP013325), followed by 90.18% identity with Labeo bata (AP011198).

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.7
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• pp.1029-1036
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• 2017

Objective: In the livestock industry, the regulatory mechanisms of muscle proliferation and differentiation can be applied to improve traits such as growth and meat production. We investigated the regulatory pathway of MyoD and its role in muscle differentiation in quail myoblast cells. Methods: The MyoD gene was mutated by the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology and single cell-derived MyoD mutant sublines were identified to investigate the global regulatory mechanism responsible for muscle differentiation. Results: The mutation efficiency was 73.3% in the mixed population, and from this population we were able to establish two QM7 MyoD knockout subline (MyoD KO QM7#4) through single cell pick-up and expansion. In the undifferentiated condition, paired box 7 expression in MyoD KO QM7#4 cells was not significantly different from regular QM7 (rQM7) cells. During differentiation, however, myotube formation was dramatically repressed in MyoD KO QM7#4 cells. Moreover, myogenic differentiation-specific transcripts and proteins were not expressed in MyoD KO QM7#4 cells even after an extended differentiation period. These results indicate that MyoD is critical for muscle differentiation. Furthermore, we analyzed the global regulatory interactions by RNA sequencing during muscle differentiation. Conclusion: With CRISPR/Cas9-mediated genomic editing, single cell-derived sublines with a specific knockout gene can be adapted to various aspects of basic research as well as in functional genomics studies.