Kim, Cheol-Jin;Park, Hyung-Yeon;Kim, Jae-Eun;Park, Hee-Jin;Lee, Bon-Su;Choi, Yu-Sang;Lee, Joon-Hee;Yoon, Je-Yong
Microbiology and Biotechnology Letters
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v.37
no.3
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pp.248-257
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2009
The inhibitors against Vibrio harveyi quorum sensing (QS) signaling were developed by modifying the molecular structure of the major signal, N-3-hydroxybutanoyl-L-homoserine lactone (3-OH-$C_4$-HSL). A series of structural derivatives, N-(3-hydroxysulfonyl)-L-homoserine lactones (HSHLs) were synthesized by the solid-phase organic synthesis method. The in vivo QS inhibition by these compounds was measured by a bioassay system using the V. harveyi bioluminescence, and all showed significant inhibitory effects. To analyze the interaction between these compounds and LuxN, a 3-OH-$C_4$-HSL receptor protein of V. harveyi, we tentatively determined the putative signal binding domain of LuxN based on the sequence homology with other acyl-HSL binding proteins, and predicted the partial 3-D structure of the putative signal binding domain of LuxN by using ORCHESTRA program, and further estimated the binding poses and energies (docking scores) of 3-OH-$C_4$-HSL and HSHLs within the domain. In comparison of the result from this modeling study with that of in vivo bioassay, we suggest that the in silica interpretation of the interaction between ligands and their receptor proteins can be a valuable way to develop better competitive inhibitors, especially in the case that the structural information of the protein is limited.
Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.
Jeong, Young Joo;Park, Sung Woo;Seo, Mi Kyoung;Kim, Sang-Jin;Lee, Won Hee;Kim, Mooseong;Urm, Sang-Hwa;Lee, Jung Goo;Seog, Dae-Hyun
Journal of Life Science
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v.31
no.3
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pp.257-265
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2021
Heterotrimeric kinesin-2 is a molecular motor protein of the kinesin superfamily (KIF) that moves along a microtubule plus-end directed motor protein. It consists of three different motor subunits (KIF3A, KIF3B, and KIF3C) and a kinesin-associated protein 3 (KAP3) that form a heterotrimeric complex. Heterotrimeric kinesin-2 interacts with many different binding proteins through the cargo-binding domain of the KIF3s. The activity of heterotrimeric kinesin-2 is regulated to ensure that the cargo is directed to the right place at the right time. How this regulation occurs, however, remains in question. To identify the regulatory proteins for heterotrimeric kinesin-2, we performed yeast two-hybrid screening and found a specific interaction with creatine kinase B (CKB), which is the brain isoform of cytosolic creatine kinase enzyme. CKB bound to the cargo-binding domain of KIF3A but did not interact with the KIF3B, KIF5B, or KAP3 in the yeast two-hybrid assay. The carboxyl (C)-terminal region of CKB is essential for the interaction with KIF3A. Another protein kinase, CaMKIIa, interacted with KIF3A, but GSK3a did not interact with KIF3A in the yeast two-hybrid assay. KIF3A interacted with GST-CKB-C but not with GSK-CKB-N or GST alone. When co-expressed in HEK-293T cells, CKB co-localized with KIF3A and co-immunoprecipitated with KIF3A and KIF3B but not KIF5B. These results suggest that the CKB-KIF3A interaction may regulate the cargo transport of heterotrimeric kinesin-2 under energy-compromised conditions in cells.
The purpose of this study was to develop a parenting intervention program and determine the efficacy of the program with low-birth weight infants and their mothers. Nine dyads for the experimental group and twelve dyads for the control group discharged from the Neonatal Intensive Care Unit of a University Hospital in Seoul were recruited for the study. For the intervention group, programmed education and support which focused on the maternal sensitivity of the infant's behavior. rearing environment. motherinfant interaction and infant care were given to each subject. Individual counseling and home visits were provided at discharge, one week after discharge. and one and three months of corrected age in every infant. Structured questionaires were administered and feeding interactions were videotaped and coded by a blinded certified observer. A Quasi-experimental design was conducted for this study. Postpartum depression, maternal self esteem. infant care burden, HOME. mother-infant interaction, and infant development were measured. Results were in favor of the intervention versus the control group. On the Beck depression inventory, intervention mothers showed decreasing trends in depressive symptom vs control mothers although, there were statistically no significant differences between the two groups at each time. The mean score of experimental group was 11.55(mild depression state) at discharge and became 8,6(normal state) at 1 month of corrected age. On the other hand, the mean score of the control group was 13.92(mild depression state) at discharge and became 14.0. Maternal self esteem in both groups improved over time. Infant care burden in both groups was also shown to increase over time. There was a significant difference between the two groups in HOME(p=.0340) at 3 months of corrected age. HOME scores of the experimental group and the control's were 31.10 and 25.58, respectively. Mothers' emotional and language responses were significantly high in the intervention group compared with the control group(p=.0155). Intervention group (53.33) showed a significantly high quality of motherinfant interaction compared with the in control group (42.80)(p =.0340). Intervention group mothers appeared have a better quality of mother-infant interaction behaviors. On the other hand, there was no statistical difference in the infant part between groups. Intervention group infants had higher trends in a general developmental quotient: although, there was no statistical difference between groups. The general developmental quotient of intervention infants was 102.56 and control's was 91.28. However, the developmental quotient of the domain of 'individuality-sociality' was higher in the intervention group infants compared with the control's(p=.0155). The concerns identified by parents revealed two domains of an infants' health management -knowledge and skills in caregiving of lowbirthweight-infants, characteristics of lowbirthweight infants, identifying a developmental milestone, coping with emergency situations and relaxation strategies of mothers from the infant care burden. Interview data with the mothers of low-birth weight infants can be used to develop intervention program contents. Limited intervention time and frequency due to time and cost limitations of this study should be modified. The intervention should be continuously implemented when low-birth weight infants become three years old. An NNNS demonstration appeared to be a very effective intervention for the mothers to improve the quality of mother-infant interactions. Therefore intervening in the mothers of low-birth weight infants as early after delivery as possible is desirable. This study has shown that home visit interventions are worthwhile for mothers only beyond the approach as an essential factor in ability of facilitating a growth fostering environment. In conclusion. the intervention program of this study was very effective in enhancing the parenting for the mothers of low-birth weight infants, resulting in health promotion of low-birth weight infants. The home-visit outreach intervention program of this study will contribute to the health delivery system in this country where there is a lack of continuous follow-up programs for low-birth weight infants after discharge from NICU, if it is activated as part of the home visit programs in community health systems.
A numerical procedure is described for estimating the effects of the multi-directional irregular waves on the structural responses of the Tension Leg Platform (TLP). The numerical approach is based on a three dimensional source distribution method for hydrodynamic forces, a three dimensional frame analysis method for structural responses, in which the superstructure of TLP is assumed to be flexible instead of rigid. Hydrodynamic and hydrostatic forces on the submerged surface of a TLP have been accurately calculated by excluding the assumption of the slender body theory. The hydrodynamic interactions among TLP members, such as columns and pontoons, and the structural damping are included in structural analysis. The spectral description used in spectral analysis of directional waves for the linear system of a TLP in the frequency domain is sufficient to completely define the structural responses. This is due to both the wave inputs and responses are stationary Gaussian random process of which the statistical properties in the amplitude domain are well known. The numerical results for the linear motion responses and tension variations in regular waves are compared with the experimental and numerical ones, which are obtained in Yoshida et al.(1983). The results of comparison confirmed the validity of the proposed approach.
Journal of the Korea Academia-Industrial cooperation Society
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v.19
no.5
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pp.418-425
/
2018
The purpose of this study was to investigate the effects of young children's empathic ability and interpersonal competence on caring behavior in forming relationships. Subjects included 152 4- and 5-year-old children attending a kindergarten located in a micropolitan city. Questionnaires required self-reporting by teachers, and were used to investigate young children's caring behavior, empathic ability and interpersonal competence in forming relationships. Data was analyzed using t-test, Pearson's correlation coefficient analysis and Stepwise-Regression analysis. Results were as follows: First, young children's caring behavior was negatively correlated with empathic ability and positively associated with interpersonal competence in forming relationships. Second, young children's emotional behavior as each domain of caring behavior were predictable variables for explaining the relative effect of the social reactivity and explaining the relative effect of relationship formation. Active behaviors were predictable variables for explaining the relative effect of follow-up instructions, but negatively affected mental burden. Normative behaviors were predictable variables for explaining the relative effect of social reactivity, but negatively predictable variables for explaining the relative effect of the relationship formation and mental burden. Value-contributing behavior in each domain of caring behavior were predictable variables for explaining the relative effect of the positive interaction.
The ubiquitin system uses ligases and deubiquitinases (DUBs) to regulate ubiquitin position on protein substrates and is involved in many biological processes which determine stability, activity, and interaction of the target substrate. DUBs are classified in six groups according to catalytic domain, namely ubiquitin-specific proteases (USPs); ubiquitin C-terminal hydrolases (UCHs); ovarian tumor proteases (OTUs); Machado Joseph Disease proteases (MJDs); motif interacting with Ub (MIU)-containing novel DUB family (MINDY); and Jab1/MPN/MOV34 metalloenzymes (JAMMs). Otubain 1 (OTUB1) is a DUB in the OTU family which possesses both canonical and non-canonical activity and can regulate multiple cellular signaling pathways. In this review, we describe the function of OTUB1 through regulation of its canonical and non-canonical activities in multiple specifically cancer-associated pathways. The canonical activity of OTUB1 inhibits protein ubiquitination by cleaving Lys48 linkages while its non-canonical activity prevents ubiquitin transfer onto target proteins through binding to E2-conjugating enzymes, resulting in the induction of protein deubiquitination. OTUB1 can therefore canonically and non-canonically promote tumor cell proliferation, invasion, and drug resistance through regulating FOXM1, ERα, KRAS, p53, and mTORC1. Moreover, clinical research has demonstrated that OTUB1 overexpresses with high metastasis in many tumor types including breast, ovarian, esophageal squamous, and glioma. Therefore, OTUB1 has been suggested as a diagnosis marker and potential therapeutic target for oncotherapy.
Kim, J.S.;Nam, B.W.;Park, S.;Kim, K.H.;Shin, S.H.;Hong, K.
Proceedings of the Korean Institute of Navigation and Port Research Conference
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2019.11a
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pp.150-152
/
2019
In this study, the effects of the wave field changes due to the coastal structure on the hydrodynamic performance of the OWC wave energy, converter are analyzed using a three-dimensional numerical wave tank technique (NWT). The OWC device is simulated numerically by introducing a linear pressure drop model, considering the coupling effect between the turbine and the OWC chamber in the time domain. The flow distribution around the chamber is different due to the change of reflection characteristics depending on the consideration of the breakwater model. The wave energy captured from the breakwater is spatially distributed on the plane of the front of the breakwater, and the converted pneumatic power increased when concentrated in front of the chamber. The change of the standing wave distribution is repeated according to the relationship between the incident wavelength and the length of the breakwater, and the difference in energy conversion performance of the OWC was confirmed.
Time expressions are a very important form of information in different types of data. Thus, the recognition of a time expression is an important factor in the field of information extraction. However, most previously designed systems consider only a specific domain, because time expressions do not have a regular form and frequently include different ellipsis phenomena. We present a two-level recognition method consisting of extraction and transformation phases to achieve generality and portability. In the extraction phase, time expressions are extracted by atomic time units for extensibility. Then, in the transformation phase, omitted information is restored using basis time and prior knowledge. Finally, every complete atomic time unit is transformed into a normalized form. The proposed system can be used as a general-purpose system, because it has a language- and domain-independent architecture. In addition, this system performs robustly in noisy data like SMS data, which include various errors. For SMS data, the accuracies of time-expression extraction and time-expression normalization by using the proposed system are 93.8% and 93.2%, respectively. On the basis of these experimental results, we conclude that the proposed system shows high performance in noisy data.
Magnetic properties of transition metal doped $La_{0.5}Ca_{0.5}(Mn_{0.98}TM_{0.02})O_3$(TM=Cr and Ti) are studied. The samples are synthesized by the conventional solid-state method. Using vibrating sample magnetometer magnetization-temperature measurement were carried out with zero field cooling and field cooling at 50 Oe. Cr-doped sample shows cluster or spin glass like behavior while Ti doped does not. Curie temperature obtained were decreased from that of LCMO(245.5 K). Curie temperatures of Cr-doped and Ti-doped samples are 235.5 K and 232.7 K, respectively. The temperature-dependent coercivity $H_c(T)$ was also measured. The coercive force continuously decreases with the substitution of Cr and Ti, The result can be understood in terms of the interaction between defect and domain wall.
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