• Tuberculosis and Respiratory Diseases
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• 제80권2호
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• pp.159-168
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• 2017

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

• 한국수산과학회지
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• 제48권1호
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• pp.71-75
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• 2015

Nicotinic acetylcholine receptors (nAChRs) are essential for neurotransmission and important therapeutic targets of diseases related to neurotransmission. A recent experimental study identified three residues (Lys185, Asp187, and Ile188) of the ${\alpha}6$ nAChR subunit as determinants of ${\alpha}$-conotoxin BuIA selectivity, yet how these residues confer toxin selectivity remains unclear. In this study, we performed all-atom molecular dynamics simulations with two toxin-bound ${\alpha}4{\beta}2$ nAChR systems: the wild-type ${\alpha}4{\beta}2$ and one in which we replaced the three ${\alpha}4$ subunit residues with three ${\alpha}6$ subunit residues identified in an experimental study (Tyr185Lys, Thr187Asp, and Arg188Ile). After mutation, Asp199 lost the salt bridge formed with Arg188 in the wild type located around loop C. Then, the loop C conformation changed and became more flexible than that of the wild type. We also detected reduced space between the toxin and the binding site in the mutant simulation, resulting in increased binding affinity to the toxin. Therefore, we propose a new Asp199 mutation that breaks the salt bridge and may produce similar selectivity to that of the Arg188 mutation.

• 종양간호연구
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• 제11권3호
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• pp.200-209
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• 2011

Purpose: The purpose of this micro-ethnography is to examine whether science and societal changes impact family communication patterns among a convenience sample of 16 Korean women. Methods: The authors observed family communication in the context of a new breast cancer genetic screening and diagnostic testing program to detect BRCA gene mutations in Korean women at highest risk. Results: Analysis of in-depth interviews and field notes taken during participant observation illustrated that communication patterns in families vary according to a woman's position in the family. If a grandmother tests positive for a gene mutation, her daughters make decisions on her behalf; they open and maintain the communication channel among family members. If a housewife is diagnosed with cancer and a genetic mutation, she immediately consults her husband and her sisters. The husband creates an open communication channel between his wife, his parents and his siblings. As a result, a woman's cancer is a concern for the whole family not merely a woman's secret or crisis. Conclusion: Cultural differences are important to consider when designing new genetic service programs in different countries.

• 한국지능시스템학회논문지
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• 제8권3호
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• pp.1-8
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• 1998

본 논문에서는 유전자 프로그래밍의 성능을 향상시키기 위하여 강화학습법에 기반한 강화 유전자 프로그래밍을 제안한다. 트리구조와 프로그램을 염색체로 가지는 유전자 프로그래밍(GP)은 다른 진화 알고리즘에 비해 염색체의 크기에 제한이 없기 때문에 표현력에 융통성이 많다는 장점이 있다. 그러나 이러한 특징은 반대고 교차 및 돌연변이 연산에 있어서 수렴성을 떨어뜨리는 단점을 나타낸다. 따라서 유전자 프로그래밍은 다른 진화알고리즘에 비해 개체군의 크기 및 진화 세대수를 크게 잡는 것이 일반적이다. 본 논문에서는 유전자 프로그래밍의 이러한 성질을 개선하기 위해서 프로그램에 강화신호를 주어 이것의 보답/벌칙의 정도에 기반한 교차 및 돌연번이 연산을 실행하는 방법을 제안한다. 제안된 방법은 인공개미(Artificial Ant)문제에 적용하여 그 유효성을 입증한다.

• 한국공간구조학회논문집
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• 제1권1호
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• pp.125-134
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• 2001

The objective of this study is the development of size discrete optimum design algorithm which is based on the GAs(genetic algorithms). The algorithm can perform size discrete optimum designs of space trusses. The developed algorithm was implemented in a computer program. For the optimum design, the objective function is the weight of space trusses and the constraints are limite state design codes(1998) and displacements. The basic search method for the optimum design is the GAs. The algorithm is known to be very efficient for the discrete optimization. This study solves the problem by introducing the GAs. The GAs consists of genetic process and evolutionary process. The genetic process selects the next design points based on the survivability of the current design points. The evolutionary process evaluates the survivability of the design points selected from the genetic process. In the genetic process of the simple GAs, there are three basic operators: reproduction, cross-over, and mutation operators. The efficiency and validity of the developed discrete optimum design algorithm was verified by applying GAs to optimum design examples.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.542-546
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• 2009

Leaves are the major biomass-producing organs in herbaceous plants and mainly develop during vegetative stage by activities of shoot apical meristem. There is a strong correlation between leaf number and bolting, a characteristic phenotype during the transition to reproductive phase in Arabidopsis thaliana. In order to study interactions between leaf number and bolting, we isolated a Landsberg erecta-derived mutant named multifolial (mfo1) that produces increased number of leaves and bolts at the same time as the wild type. Through positional cloning and allelism test, mfo1 was found to be an allele of a previously reported mutant, altered meristem program1-1 (amp1-1) that is defective in a glutamate carboxypeptidase and bolts earlier than its wild type, Columbia ecotype, with the increased number of leaves. The bolting time differences between mfo1 and amp1, despite the same phenotype of many leaves, suggest the existence of genetic factor(s) differently function in each ecotype in the presence of mfo1/amp1 mutation.

• BMB Reports
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• 제47권1호
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• pp.15-20
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• 2014

Intracellular lipid-binding proteins (LBPs) impact fatty acid homeostasis in various ways, including fatty acid transport into mitochondria. However, the physiological consequences caused by mutations in genes encoding LBPs remain largely uncharacterized. Here, we explore the metabolic consequences of lbp-5 gene deficiency in terms of energy homeostasis in Caenorhabditis elegans. In addition to increased fat storage, which has previously been reported, deletion of lbp-5 attenuated mitochondrial membrane potential and increased reactive oxygen species levels. Biochemical measurement coupled to proteomic analysis of the lbp-5(tm1618) mutant revealed highly increased rates of glycolysis in this mutant. These differential expression profile data support a novel metabolic adaptation of C. elegans, in which glycolysis is activated to compensate for the energy shortage due to the insufficient mitochondrial ${\beta}$-oxidation of fatty acids in lbp-5 mutant worms. This report marks the first demonstration of a unique metabolic adaptation that is a consequence of LBP-5 deficiency in C. elegans.

• BMB Reports
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• 제57권1호
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• pp.30-39
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• 2024

Directed evolution (DE) of desired locus by targeted random mutagenesis (TRM) tools is a powerful approach for generating genetic variations with novel or improved functions, particularly in complex genomes. TRM-based DE involves developing a mutant library of targeted DNA sequences and screening the variants for the desired properties. However, DE methods have for a long time been confined to bacteria and yeasts. Lately, CRISPR/Cas and DNA deaminase-based tools that circumvent enduring barriers such as longer life cycle, small library sizes, and low mutation rates have been developed to facilitate DE in native genetic environments of multicellular organisms. Notably, deaminase-based base editing-TRM (BE-TRM) tools have greatly expanded the scope and efficiency of DE schemes by enabling base substitutions and randomization of targeted DNA sequences. BE-TRM tools provide a robust platform for the continuous molecular evolution of desired proteins, metabolic pathway engineering, creation of a mutant library of desired locus to evolve novel functions, and other applications, such as predicting mutants conferring antibiotic resistance. This review provides timely updates on the recent advances in BE-TRM tools for DE, their applications in biology, and future directions for further improvements.

• Genomics & Informatics
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• 제20권2호
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• pp.21.1-21.14
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• 2022

The influenza A viruses have high mutation rates and cause a serious health problem worldwide. Therefore, this study focused on genome characterization of the viruses isolated from Thai patients based on the next-generation sequencing technology. The nasal swabs were collected from patients with influenza-like illness in Thailand during 2017-2018. Then, the influenza A viruses were detected by reverse transcription-quantitative polymerase chain reaction and isolated by MDCK cells. The viral genomes were amplified and sequenced by Illumina MiSeq platform. Whole genome sequences were used for characterization, phylogenetic construction, mutation analysis and nucleotide diversity of the viruses. The result revealed that 90 samples were positive for the viruses including 44 of A/H1N1 and 46 of A/H3N2. Among these, 43 samples were successfully isolated and then the viral genomes of 25 samples were completely amplified. Finally, 17 whole genomes of the viruses (A/H1N1, n=12 and A/H3N2, n=5) were successfully sequenced with an average of 232,578 mapped reads and 1,720 genome coverage per sample. Phylogenetic analysis demonstrated that the A/H1N1 viruses were distinguishable from the recommended vaccine strains. However, the A/H3N2 viruses from this study were closely related to the recommended vaccine strains. The nonsynonymous mutations were found in all genes of both viruses, especially in hemagglutinin (HA) and neuraminidase (NA) genes. The nucleotide diversity analysis revealed negative selection in the PB1, PA, HA, and NA genes of the A/H1N1 viruses. High-throughput data in this study allow for genetic characterization of circulating influenza viruses which would be crucial for preparation against pandemic and epidemic outbreaks in the future.

• IMMUNE NETWORK
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• 제21권6호
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• pp.38.1-38.8
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• 2021

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.