• BMB Reports
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• 제41권6호
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• pp.415-434
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• 2008

Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-$\beta$, -$\gamma$, -$\delta$, -$\varepsilon$, -$\zeta$ and -$\eta$. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.

• 한국지진공학회논문집
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• 제26권5호
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• pp.191-202
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• 2022

Markov envelope as a theoretical solution of the parabolic wave equation with Markov approximation for the von Kármán type random medium is studied and approximated with the convolution of two probability density functions (pdf) of normal and gamma distributions considering the previous studies on the applications of Radiative Transfer Theory (RTT) and the analysis results of earthquake records. Through the approximation with gamma pdf, the constant shape parameter of 2 was determined regardless of the source distance r_o. This finding means that the scattering process has the property of an inhomogeneous single-scattering Poisson process, unlike the previous studies, which resulted in a homogeneous multiple-scattering Poisson process. Approximated Markov envelope can be treated as the normalized mean square (MS) envelope for ground acceleration because of the flat source Fourier spectrum. Based on such characteristics, the path duration is estimated from the approximated MS envelope and compared to the empirical formula derived by Boore and Thompson. The results clearly show that the path duration increases proportionately to r_o^1/2-r_o², and the peak value of the RMS envelope is attenuated by exp (-0.0033r_o), excluding the geometrical attenuation. The attenuation slope for r_o≤100 km is quite similar to that of effective attenuation for shallow crustal earthquakes, and it may be difficult to distinguish the contribution of intrinsic attenuation from effective attenuation. Slowly varying dispersive delay, also called the medium effect, represented by regular pdf, governs the path duration for the source distance shorter than 100 km. Moreover, the diffraction term, also called the distance effect because of scattering, fully controls the path duration beyond the source distance of 300 km and has a steep gradient compared to the medium effect. Source distance 100-300 km is a transition range of the path duration governing effect from random medium to distance. This means that the scattering may not be the prime cause of peak attenuation and envelope broadening for the source distance of less than 200 km. Furthermore, it is also shown that normal distribution is appropriate for the probability distribution of phase difference, as asserted in the previous studies.

• 한국ITS학회 논문지
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• 제20권5호
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• pp.35-44
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• 2021

최근 고속도로 본선구간에서 발생한 교통사고에 대한 연구가 다수 수행되고 있으나, 램프와 같이 본선 외 구간에 대한 교통안전을 다루는 연구는 미미한 실정이다. 최근 5년(2015년~2019년)동안 램프에서 발생한 사고는 총 6,717건으로 이는 전체 고속도로 사고의 약 15%를 차지한다. 본 연구에서는 고속도로 램프구간에 대해 보다 정확한 사고 예측 모형을 제공하기 위해 포아송 감마(PG)와 포아송 역가우스(PIG)와 같은 다양한 통계 분포를 비롯하여 랜덤효과와 같은 기법을 적용하여 Simple 및 Full SPF를 구축하고 비교하였다. 교통 및 도로 기하구조 데이터는 로드뷰와 같은 다양한 시스템에서 수집되었다. 분석 결과, PIG 모형은 일반적으로 더 정확한 사고 예측을 제시하며, Simpe SPF와 Full SPF 모두에서 임의효과 모형이 더욱 우수한 성능을 나타내었다. 본 연구결과는 교통실무자들에게 정확한 사고 예측 모형을 기반으로 램프구간 교통안전을 증대시키고 이해할 수 있는 참고자료로써 활용될 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.695-702
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• 2017

The sustained tonic currents ($I_{tonic}$) generated by ${\gamma}$-aminobutyric acid A receptors ($GABA_{A}Rs$) are implicated in diverse age-dependent brain functions. While various mechanisms regulating $I_{tonic}$ in the hippocampus are known, their combined role in $I_{tonic}$ regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in $GABA_AR{\alpha}_5$ subunit, resulted in various $I_{tonic}$ in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile ($P_{6-8}$ and $P_{13-15}$) and juvenile ($P_{20-22}$ and $P_{27-29}$) stages, with stabilization observed thereafter in adolescents ($P_{34-36}$) and young adults ($P_{41-43}$). $I_{tonic}$ facilitation of a selective GAT-1 blocker (NO-711) was significantly less at $P_{6-8}$ than after $P_{13-15}$. The facilitation of $I_{tonic}$ by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, $I_{tonic}$ in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by $I_{tonic}$ changes in the presence of exogenous GABA. $I_{tonic}$ sensitivity to L-655,708, a $GABA_AR{\alpha}_5$ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the $GABA_AR{\alpha}_5$ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the $I_{tonic}$ regulation of altered GATs is under the final tune of $GABA_AR{\alpha}_5$ subunit activation in DGGCs at different ages.

• Journal of Ginseng Research
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• 제42권4호
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• pp.401-411
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• 2018

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

• Journal of Ginseng Research
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• 제46권6호
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• pp.759-770
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• 2022

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD⁺-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.