• Bulletin of the Korean Chemical Society
• /
• v.30 no.5
• /
• pp.1152-1156
• /
• 2009

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

• Molecules and Cells
• /
• v.43 no.7
• /
• pp.645-661
• /
• 2020

Leaf senescence is a developmental process by which a plant actively remobilizes nutrients from aged and photosynthetically inefficient leaves to young growing ones by disassembling organelles and degrading macromolecules. Senescence is accelerated by age and environmental stresses such as prolonged darkness. Phytochrome B (phyB) inhibits leaf senescence by inhibiting phytochrome-interacting factor 4 (PIF4) and PIF5 in prolonged darkness. However, it remains unknown whether phyB mediates the temperature signal that regulates leaf senescence. We found the light-activated form of phyB (Pfr) remains active at least four days after a transfer to darkness at 20℃ but is inactivated more rapidly at 28℃. This faster inactivation of Pfr further increases PIF4 protein levels at the higher ambient temperature. In addition, PIF4 mRNA levels rise faster after the transfer to darkness at high ambient temperature via a mechanism that depends on ELF3 but not phyB. Increased PIF4 protein then binds to the ORE1 promoter and activates its expression together with ABA and ethylene signaling, accelerating leaf senescence at high ambient temperature. Our results support a role for the phy-PIF signaling module in integrating not only light signaling but also temperature signaling in the regulation of leaf senescence.

• Journal of Life Science
• /
• v.16 no.3 s.76
• /
• pp.454-458
• /
• 2006

HSF1 is the heat shock transcription factor in Saccharomyces cerevisiae. S. cerevisiae KNU5377 can ferment at high temperature such as $40^{\b{o}}C$. We have been the subjects of intense study because Hsf1p mediates gene expression not only to heat shock, but to a variety of cellular and environmental stress challenges. Basing these facts, we firstly tried to construct the hsf1 gene-deleted mutant. PCR-method for fast production of gene disruption cassette was introduced in a thermotolerant yeast S. cerevisiae KNU5377, which allowed the addition of short flanking homology region as short as 45 bp suffice to mediate homologous recombination to kanMX module. Such a cassette is composed of linking genomic DNA of target gene to the selectable marker kanMX4 that confers geneticin (G418) resistance in yeast. That module is extensively used for PCR-based gene replacement of target gene in the laboratory strains. We describe here the generation of hsf1 gene disruption construction using PCR product of selectable marker with primers that provide homology to the hsf1 gene following separation of haploid strain in wild type yeast S. cerevisiae KNU5377. Yeast deletion overview containing replace cassette module, deletion mutant construction and strain confirmation in this study used Saccharomyces Genome Deletion Project (http:://www-sequence.standard.edu/group/yeast_deletion_project). This mutant by genetic manipulation of wild type yeast KNU5377 strain will provide a good system for analyzing the research of the molecular biology underlying their physiology and metabolic process under fermentation and improvement of their fermentative properties.

• Proceedings of the Korea Information Processing Society Conference
• /
• 2013.11a
• /
• pp.1117-1120
• /
• 2013

사람의 질병은 여러 요인의 복합적인 작용으로 발생하는데 이 중 유전적인 요인에는 유전자 간의 상호작용을 들 수 있다. 마이크로어레이(Microarray) 데이터로부터 유전자의 활성화 및 억제 관계를 밝히려는 다양한 시도는 계속되어왔다. 그러나 마이크로어레이 자체가 갖는 불안정성과 실험조건 수의 제약이 커다란 장애가 되어 왔다. 이에 생물학적 사전 지식을 포함하는 방법들이 제안되었다. 본 논문에서는 질병과 관련된 유전자 간의 상호작용의 집합을 질병 모듈이라 정의하고 이를 유전자 알고리즘으로 학습한 베이지안 네트워크(Bayesian network)로 추론하는 방법을 제안한다.

• Journal of KIISE:Software and Applications
• /
• v.35 no.6
• /
• pp.347-356
• /
• 2008

High-throughput microarray is one of the most popular tools in molecular biology, and various computational methods have been developed for the microarray data analysis. While the computational methods easily extract significant features, it suffers from inferring modules of multiple co-regulated genes. Hypernetworhs are motivated by biological networks, which handle all elements based on their combinatorial processes. Hence, the hypernetworks can naturally analyze the biological effects of gene combinations. In this paper, we introduce a hypernetwork classifier for microRNA (miRNA) profile analysis based on microarray data. The hypernetwork classifier uses miRNA pairs as elements, and an evolutionary learning is performed to model the microarray profiles. miTNA modules are easily extracted from the hypernetworks, and users can directly evaluate if the miRNA modules are significant. For experimental results, the hypernetwork classifier showed 91.46% accuracy for miRNA expression profiles on multiple human canters, which outperformed other machine learning methods. The hypernetwork-based analysis showed that our approach could find biologically significant miRNA modules.

• Proceedings of the Korean Vacuum Society Conference
• /
• 2016.02a
• /
• pp.195.1-195.1
• /
• 2016

Currently, as Plasma application is expanded to the industrial and medical industrial, low temperature plasma applications became important. Especially in medical and biology, many researchers have studied about generated radical species in atmospheric pressure low temperature plasma directly adapted to human body. Therefore, so measurement their plasma parameter is very important work and is widely studied all around world. One of the plasma parameters is electron density and it is closely relative to radical production through the plasma source. some kinds of method to measuring the electron density are Thomson scattering spectroscopy and Millimeter-wave transmission measurement. But most methods have very expensive cost and complex configuration to composed of experiment system. We selected Michelson interferometer system which is very cheap and simple to setting up, so we tried to measuring electron density by laser interferometer with laser beam chopping module for measurement of temporal phase difference in plasma jet. To measuring electron density at atmospheric pressure Ar plasma jet, we obtained the temporal phase shift signal of interferometer. Phase difference of interferometer can occur because of change by refractive index of electron density in plasma jet. The electron density was able to estimate with this phase difference values by using physical formula about refractive index change of external electromagnetic wave in plasma. Our guiding laser used Helium-Neon laser of the centered wavelength of 632 nm. We installed chopper module which can make a 4kHz pulse laser signal at the laser front side. In this experiment, we obtained more exact synchronized phase difference between with and without plasma jet than reported data at last year. Especially, we found the phase difference between time range of discharge current. Electron density is changed from Townsend discharge's electron bombardment, so we observed the phase difference phenomenon and calculated the temporal electron density by using phase shift. In our result, we suggest that the electron density have approximately range between 1014~ 1015 cm-3 in atmospheric pressure Ar plasma jet.

• Smart Structures and Systems
• /
• v.8 no.1
• /
• pp.119-137
• /
• 2011

A bio-inspired two-mode structural health monitoring (SHM) system based on the Na$\ddot{i}$ve Bayes (NB) classification method is discussed in this paper. To implement the molecular biology based Deoxyribonucleic acid (DNA) array concept in structural health monitoring, which has been demonstrated to be superior in disease detection, two types of array expression data have been proposed for the development of the SHM algorithm. For the micro-vibration mode, a two-tier auto-regression with exogenous (AR-ARX) process is used to extract the expression array from the recorded structural time history while an ARX process is applied for the analysis of the earthquake mode. The health condition of the structure is then determined using the NB classification method. In addition, the union concept in probability is used to improve the accuracy of the system. To verify the performance and reliability of the SHM algorithm, a downscaled eight-storey steel building located at the shaking table of the National Center for Research on Earthquake Engineering (NCREE) was used as the benchmark structure. The structural response from different damage levels and locations was collected and incorporated in the database to aid the structural health monitoring process. Preliminary verification has demonstrated that the structure health condition can be precisely detected by the proposed algorithm. To implement the developed SHM system in a practical application, a SHM prototype consisting of the input sensing module, the transmission module, and the SHM platform was developed. The vibration data were first measured by the deployed sensor, and subsequently the SHM mode corresponding to the desired excitation is chosen automatically to quickly evaluate the health condition of the structure. Test results from the ambient vibration and shaking table test showed that the condition and location of the benchmark structure damage can be successfully detected by the proposed SHM prototype system, and the information is instantaneously transmitted to a remote server to facilitate real-time monitoring. Implementing the bio-inspired two-mode SHM practically has been successfully demonstrated.

• Molecules and Cells
• /
• v.40 no.1
• /
• pp.17-23
• /
• 2017

Mitogen-activated protein kinase (MAPK) signaling cascades play critical roles in various cellular events in plants, including stress responses, innate immunity, hormone signaling, and cell specificity. MAPK-mediated stress signaling is also known to negatively regulate nitrogen-fixing symbiotic interactions, but the molecular mechanism of the MAPK signaling cascades underlying the symbiotic nodule development remains largely unknown. We show that the MtMKK5-MtMPK3/6 signaling module negatively regulates the early symbiotic nodule formation, probably upstream of ERN1 (ERF Required for Nodulation 1) and NSP1 (Nod factor Signaling Pathway 1) in Medicago truncatula. The overexpression of MtMKK5 stimulated stress and defense signaling pathways but also reduced nodule formation in M. truncatula roots. Conversely, a MAPK specific inhibitor, U0126, enhanced nodule formation and the expression of an early nodulation marker gene, MtNIN. We found that MtMKK5 directly activates MtMPK3/6 by phosphorylating the TEY motif within the activation loop and that the MtMPK3/6 proteins physically interact with the early nodulation-related transcription factors ERN1 and NSP1. These data suggest that the stress signaling-mediated MtMKK5/MtMPK3/6 module suppresses symbiotic nodule development via the action of early nodulation transcription factors.

• Journal of Korean Neurosurgical Society
• /
• v.65 no.1
• /
• pp.4-12
• /
• 2022

Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2003.10a
• /
• pp.98-98
• /
• 2003

Recently, human embryonic stem (hES) cells have become very important resources for ES cell basic research, cell replacement therapy, and other medical applications; thus, efficient cryopreservation methods for these cells are needed. This study examined whether a newly developed minimum volume cooling (MVC) vitrification method, which was tested through cryopreservation of sensitive bovine oocytes, can be used for freezing hES cells. Feeder-free cultured hES cell (MB03) colonies were mechanically dissected into several small clumps following enzymatic treatment. We compared the freezing efficiency of a slow-cooling method using a cryo-module (0.4-0.6C/min, 20-30 clumps/vial) and MVC vitrification using a modified 0.5-ml French mini-straw designated as a MVC straw (>$20,000{\circ}C$/min, 10 clumps/straw) After thawing, in vitro survival of hES cell clumps was higher for MVC-vitrified cells (80.8%, 97/120) than for slow-cooled cells (38.2%, 39/102). Further, the proliferation rate of surviving MVC-vitrified cells was similar to that of control hES cells from 2 weeks after thawing. In addition, vitrified-thawed hES cells demonstrated a normal karyotype, were positively immunostained for surface marker antibodies (AP, SSEA-4 and TRA-1-60) and the Oct-4 antibody, and could differentiate into all three embryonic germ layer cells in vitro. This result demonstrates that hES cell clumps can be successfully cryopreserved by a newly developed MVC vitrification method without loss of human cell characteristics.