• Journal of Genetic Medicine
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• v.5 no.2
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• pp.89-93
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• 2008

"Personalized medicine," the goal of which is to provide better clinical care by applying patient's own genomic information to their health care is a global challenge for the $21^{st}$ century "genomic era." This is especially true in Korea, where provisions for clinical genetic services are inadequate for the existing demand, let alone future demands. Genomics-based knowledge and tools make it possible to approach each patient as a unique biological individual, which has led to a paradigm-shift in medical practice, giving it more of a predictive focus as compared with current treatment oriented approach. With recent advancements in genomics, many genetic tests, such as susceptibility genetic tests, have been developed for both rare single gene diseases and more common multifactorial diseases. Indeed, genetic tests for presymtomatic individuals and genetic tests for drug response have become widely available, and personalized medicine will face the challenge of assisting patients who use such tests to make appropriate and wise use of genetic risk assessment. A major challenge of genomic medicine lies in understanding and communicating disease risk in order to facilitate and support patients and their families in making informed decisions. Establishment of a health care system with provisions for genetic counseling as an integral part of health care service, in addition to genomic literacy of health care providers, is vital to meet this growing challenge. Realization of the promise of personalized medicine in the era of genomics for improvement of health care is dependent on further development of next generation sequencing technology and affordable sequencing test costs. Also necessary will be policy development concerning the ethical, legal and social issues of genomic medicine and an educated and ready medical community with clinical practice guidelines for genetic counseling and genetic testing.

• Journal of Genetic Medicine
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• v.11 no.1
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• pp.1-10
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• 2014

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic ${\beta}$-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against ${\beta}$-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.

• Archives of Pharmacal Research
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• v.17 no.2
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• pp.100-103
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• 1994

The limonoid compound (28-deacetyl sendanin0 isolated from the fruit of Melia toosendan SIEB. et ZUCC. was evaluated on anticancer activity. According to a standard in vitro cytotoxicity assy, eight human cancer cell lines and SRB assay were introduced for present evaluation. As a positive standard, adriamycin was tested in parallel. The cell lines were originated from six different organs. In view of dose-response profiles to 28-deacetyl sendanin, the most sensitive cells were SF-539 and PC-3 which were derived from CNS and prostate, respecitively. In contrast, all the cell lines responded similarly to adriamycin to give rise to nearly indentical six cell lines were more sensitive to 28-deacetyl sendanin and two were more resistant. As a result, 28-deacetyl sendanin had more senstive and selective inhibitory effects on in vitro growth of human cancer cell lines in a comparison with adriamycin.

• International Journal of Naval Architecture and Ocean Engineering
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• v.7 no.4
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• pp.750-769
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• 2015

The geometry of engineering systems affects their performances. For this reason, the shape of engineering systems needs to be optimized in the initial design stage. However, engineering system design problems consist of multi-objective optimization and the performance analysis using commercial code or numerical analysis is generally time-consuming. To solve these problems, many engineers perform the optimization using the approximation model (response surface). The Response Surface Method (RSM) is generally used to predict the system performance in engineering research field, but RSM presents some prediction errors for highly nonlinear systems. The major objective of this research is to establish an optimal design method for multi-objective problems and confirm its applicability. The proposed process is composed of three parts: definition of geometry, generation of response surface, and optimization process. To reduce the time for performance analysis and minimize the prediction errors, the approximation model is generated using the Backpropagation Artificial Neural Network (BPANN) which is considered as Neuro-Response Surface Method (NRSM). The optimization is done for the generated response surface by non-dominated sorting genetic algorithm-II (NSGA-II). Through case studies of marine system and ship structure (substructure of floating offshore wind turbine considering hydrodynamics performances and bulk carrier bottom stiffened panels considering structure performance), we have confirmed the applicability of the proposed method for multi-objective side constraint optimization problems.

• Animal cells and systems
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• v.16 no.4
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• pp.280-288
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• 2012

Targeted degradation of proteins through ubiquitin-mediated proteolysis is an important control mechanism in various cellular processes. The process of ubiquitin conjugation is achieved by three enzyme complexes, among which the ubiquitin ligase complex (E3) is in charge of substrate specificity. The SCF (SKP1-CUL1-F-box) family portrays the largest and the most characterized member of the E3 ligases. For each SCF complex, the ubiquitination target is recognized by the F-box protein subunit, which interacts with the substrate through a unique C-terminal domain. We have characterized a novel F-box protein CFL-1 that represents a single LRR-type F-box (FBXL) in the Caenorhabditis elegans genome. CFL-1 is highly homologous to FBXL20 and FBXL2 of mammals, which are known to regulate synaptic vesicle release and cell cycle, respectively. A green fluorescence protein (GFP)-reporter gene fused to the cfl-1 promoter showed restricted expression around the amphid and the anus. Modulation of CFL-1 activity by RNAi affected the time interval between defecations. RNAi-treated worms also exhibited reduced tendency to form dauer when exposed to daumone. The potential involvement of CFL-1 in the control of defecation and pheromone response adds to the ever expanding list of cellular processes controlled by ubiquitin-mediated proteolysis in C. elegans. We suggest that CFL-1, as a single LRR-type F-box protein in C. elegans, may portray a prototype gene exerting diverse functions that are allocated among multiple FBXLs in higher organisms.

• Animal Bioscience
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• v.34 no.4
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• pp.499-505
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• 2021

Objective: The objective of this study was to evaluate the genetic behavior of a population of Holstein cattle in response to the variation of environmental temperature by analyzing the effects of genotype by environment interaction (GEI) through reaction norms for the somatic cell score (SCS). Methods: Data was collected for 67,206 primiparous cows from the database of the Paraná Holstein Breeders Association in Brazil, with the aim of evaluating the temperature effect, considered as an environmental variable, distinguished under six gradients, with the variation range found being 17℃ to 19.5℃, over the region. A reaction norm model was adopted utilizing the fourth order under the Legendre polynomials, using the mixed models of analysis by the restricted maximum likelihood method by the WOMBAT software. Additionally, the genetic behavior of the 15 most representative bulls was assessed, in response to the changes in the temperature gradient. Results: A mean score of 2.66 and a heritability variation from 0.17 to 0.23 was found in the regional temperature increase. The correlation between the environmental gradients proved to be higher than 0.80. Distinctive genetic behaviors were observed according to the increase in regional temperature, with an observed increase of up to 0.258 in the breeding values of some animals, as well as a reduction in the breeding of up to 0.793, with occasional reclassifications being observed as the temperature increased. Conclusion: Non-relevant GEI for SCS were observed in Holstein cattle herds of southern Brazil. Thus, the inclusion of the temperature effect in the model of genetic evaluation of SCS for the southern Brazilian Holstein breed is not required.

• Animal Bioscience
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• v.37 no.1
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• pp.61-73
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• 2024

Objective: The main objective of this study was to define molecular mechanisms associated with thermal stress responses of chickens from commercial broilers (BR, Ross 308), Thai native chickens (NT) and crossbreeds between BR×NT (H75). Methods: Twenty days before reaching specific market age, chickens from each breed were divided into control and thermal-stressed groups. The stressed groups were exposed to a cyclic thermal challenge (35℃±1℃ for 6 h, followed by 26℃±1℃ for 18 h) for 20 days. Control group was raised under a constant temperature of 26℃±1℃. Pectoralis major (n = 4) from each group was collected for transcriptome analysis using HiSeq Illumina and analysis of glycogen and lactate. Gene expression patterns between control and thermal-stressed groups were compared within the same breeds. Results: Differentially expressed transcripts of 65, 59, and 246 transcripts for BR, NT, and H75, respectively, were revealed by RNA-Seq and recognized by Kyoto encyclopedia of genes and genomes database. Pathway analysis underlined altered glucose homeostasis and protein metabolisms in all breeds. The signals centered around phosphatidylinositol 3-kinase (PI3K)/Akt signaling, focal adhesion, and MAPK signaling in all breeds with slight differences in molecular signal transduction patterns among the breeds. An extensive apoptosis was underlined for BR. Roles of AMPK, MAPK signaling and regulation of actin cytoskeleton in adaptive response were suggested for H75 and NT chickens. Lower glycogen content was observed in the breast muscles of BR and NT (p<0.01) compared to their control counterparts. Only BR muscle exhibited increased lactate (p<0.01) upon exposure to the stress. Conclusion: The results provided a better comprehension regarding the associated biological pathways in response to the cyclic thermal stress in each breed and in chickens with different growth rates.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.40 no.3
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• pp.10-17
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• 2003

In this paper, genetic algorithm (GA)-based Thin Film Bulk Acoustic Resonator (FBAR) RF filter design technique is proposed. Since the BVD(Butterworth-Van Dyke) lumped element model is valid only around the resonance, FBAR filter design technique based on BVD circuit has an approximate error. Instead of using BVD model, optimizing filter design method utilizes an analytical electrical impedance equation of FBAR. The geometry of FBAR such as thickness of the piezoelectric layer and area which significantly affect the filter response is optimized by GA. US-PCS Rx Bandpass filter obtained by the proposed technique shows a better response comparing with the typical and BVD-based filter.

• Toxicological Research
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• v.34 no.4
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• pp.303-310
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• 2018

The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.

• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1852-1859
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• 2019

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN-β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.