• Title/Summary/Keyword: Rate Limiting

Search Result 752, Processing Time 0.037 seconds

Selective cytotoxicity of a novel mitochondrial complex I inhibitor, YK-135, against EMT-subtype gastric cancer cell lines due to impaired glycolytic capacity

  • Yeojin, Sung;Seungbin, Cha;Sang Bum, Kim;Hakhyun, Kim;Seonghwi, Choi;Sejin, Oh;Minseo, Kim;Yunji, Lee;Gino, Kwon;Jooyoung, Lee;Joo-Youn, Lee;Gyoonhee, Han;Hyun Seok, Kim
    • BMB Reports
    • /
    • v.55 no.12
    • /
    • pp.645-650
    • /
    • 2022
  • Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

Open BIS Platform and Business Model Development for Providing Bus Information in the Area (지역의 버스정보 제공을 위한 Open BIS 플랫폼 및 비즈니스 모델 개발)

  • Won pyoung Kang;Yung sung Cho;Seung neo Son;Hyo kyung Eo;Kyung suk Kim
    • The Journal of The Korea Institute of Intelligent Transport Systems
    • /
    • v.23 no.1
    • /
    • pp.97-111
    • /
    • 2024
  • Developing countries and small local governments face financial constraints, limiting the adoption of their own bus information systems. However, despite poor social infrastructure and low income levels, developing countries have a high smartphone penetration rate, and the distribution and usage of online content and social media are widespread. Smartphones, equipped with GPS sensors, cameras, and other location-based information collection capabilities, can replace expensive on-site terminals. This study aims to replace expensive on-site terminals with smartphones, develop a center system based on cloud servers, and establish an extensible Open BIS (Bus Information System) service and platform that can be applied anywhere. The goal is to formulate a business model in the process.

Effects of Running Speed on Body Impact Acceleration and Biomechanical Variables (달리기 속도의 변화가 인체 충격 가속도와 생체역학적 변인에 미치는 영향)

  • Young-Seong Lee;Jae-Won Kang;Sang-Kyoon Park
    • Korean Journal of Applied Biomechanics
    • /
    • v.34 no.2
    • /
    • pp.81-92
    • /
    • 2024
  • Objective: The purpose of this study was to analyze the impact acceleration, shock attenuation and biomechanical variables at various running speed. Method: 20 subjects (height: 176.15 ± 0.63 cm, weight: 70.95 ± 9.77 kg, age: 27.00 ± 4.65 yrs.) participated in this study. The subjects ran at four different speeds (2.5 m/s, 3.0 m/s, 3.5 m/s, 4.0 m/s). Three-dimensional accelerometers were attached to the distal tibia, sternum and head. Gait parameters, biomechanical variables (lower extremity joint angle, moment, power and ground reaction force) and acceleration variables (impact acceleration, shock attenuation) were calculated during the stance phase of the running. Repeated measures ANOVA was used with an alpha level of .05. Results: In gait parameters, decreased stance time, increasing stride length and stride frequency with increasing running speed. And at swing time 2.5 m/s and 4.0 m/s was decreased compared to 3.0 m/s and 3.5 m/s. Biomechanical variables statistically increased with increasing running speed except knee joint ROM, maximum ankle dorsiflexion moment, and maximum hip flexion moment. In acceleration variables as the running speed increased (2.5 m/s to 4.0 m/s), the impact acceleration on the distal tibia increased by more than twice, while the sternum and head increased by approximately 1.1 and 1.2 times, respectively. And shock attenuation (tibia to head) increased as the running speed increased. Conclusion: When running speed increases, the magnitude and increasing rate of sternum and head acceleration are lower compared to the proximal tibia, while shock attenuation increases. This suggests that limiting trunk movement and increasing lower limb movement effectively reduce impact from increased shock. However, to fully understand the body's mechanism for reducing shock, further studies are needed with accelerometers attached to more segments to examine their relationship with kinematic variables.

Effects of Amomum Villosum Extracts on Cholesterol Synthesis in HepG2 Cells (양춘사 추출물이 HepG2 세포에서 콜레스테롤 합성에 미치는 효과)

  • Ha Rim Kim;Ye Seul Kim;Han Byeol Choi;Su Hyeon Woo;Kang Beom Kwon
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.38 no.1
    • /
    • pp.27-31
    • /
    • 2024
  • Dried fruits of Amomum villosum Lour. have been used an korean medicine to treat digestive diseases for a long time. It has been reported that Amomum villosum extracts(AVE) have effects for diabetes and steatosis in experimental models. But we did not find the report about the cholesterol synthesis inhibition effects of AVE. The objective of this study is to clarify the inhibitory effect of AVE against oleic acid and glucose-induced hypercholesterolemia in HepG2 cells. The results show that AVE had a significant inhibitory effect against oleic acid and glucose-induced cholesterol accumulation. Those effects seem to be caused by inhibition of AVE on oleic acid and glucose-induced decrease of HMG CoA reductase, which is the rate-limiting enzyme for cholesterol biosynthesis in liver. It is believed that the results of this study can provide basic data for the drug and functional food development of hypercholesterolemia treatments.

Seroprevalence and risk factors of sheep and goat pox virus in selected districts of Wolaita Zone, Southern Ethiopia

  • Fentaye Kassa;Haben Fesseha;Mesfin Mathewos;Selenat Getachew;Nato Hundessa;Saliman Aliye;Isayas Asefa Kebede
    • Journal of Veterinary Science
    • /
    • v.25 no.4
    • /
    • pp.57.1-57.12
    • /
    • 2024
  • Importance: Sheep and goat pox (SGP) virus infection is a highly fatal viral infection of small ruminants that causes major production losses in sheep and goats in Ethiopia while also limiting international trade. Objective: This study aimed to estimate the seroprevalence of SGP infection and assess related risk variables. Methods: A cross-sectional study was conducted from February to August 2023 on 384 serum samples taken from sheep and goats. A serum neutralization test was conducted to detect the presence of antibodies against the SGP virus in Wolaita Sodo Regional Laboratory. Results: The overall seroprevalence rate of SGP was 4.95%. Factors such as sheep (8.26%), female sheep and goats (7.45%), older sheep and goats (8.33%), larger flock size of sheep and goats (10.47%), poorly conditioned sheep and goats (31.58%), sheep and goats with a tick on their skin (10.38%), and animals that had not been vaccinated (5.17%) were found to have higher seroprevalence. Furthermore, the seropositivity in sheep was five times greater than in goats (adjusted odds ratio [AOR], 4.73; 95% confidence interval [CI], 1.39-15.99). Additionally, large-sized flocks of sheep and goats were more likely to be seropositive to pox disease than small-sized flocks (AOR, 6.73; 95% CI, 1.58-28.67). Conclusions and Relevance: Thus, the study revealed the prevalence of SGP in the Wolaita zone. Additional research should be conducted to estimate the extent of the disease at the regional level, and management measures should be implemented to reduce the economic losses associated with this condition.

A study of an oyster monthly forecasting model using the structural equation model approach based on a panel analysis

  • Sukho Han;Seonghwan Song;Sujin Heo;Namsu Lee
    • Korean Journal of Agricultural Science
    • /
    • v.49 no.4
    • /
    • pp.1001-1013
    • /
    • 2022
  • The purpose of this study is to build an oyster outlook model. In particular, by limiting oyster items, it was designed as a partial equilibrium model based on a panel analysis of a fixed effect model on aquaculture facilities. The model was built with a dynamic ecological equation (DEEM) system that considers aquaculture and harvesting processes. As a result of the estimation of the initial aquaculture facilities based on the panel analysis, the elasticity of the remaining facility volume in the previous month was estimated to be 0.63. According to Nerlove's model, the adjustment coefficient was interpreted as 0.31 and the adjustment speed was analyzed to be very slow. Also, the relative income coefficient was estimated to be 2.41. In terms of elasticity, it was estimated as 0.08% in Gyeongnam, 0.32% in Jeonnam, and 1.98% in other regions. It was analyzed that the elasticity of relative income was accordingly higher in non-main production area. In case of the estimation of the monthly harvest facility volume, the elasticity of the remaining facility volume in the previous month was estimated as 0.53, and the elasticity of the farm-gate price was estimated as 0.23. Both fresh and chilled and frozen oysters' exports were estimated to be sensitive to fluctuations in domestic prices and exchange rates, while Japanese wholesale prices were estimated to be relatively low in sensitivity, especially to the exchange rate with Japan. In estimating the farm-gate price, the price elasticity coefficient of monthly production was estimated to be inelastic at 0.25.

Review of the study on the surfactant-induced foliar uptake of pesticide (계면활성제에 의해 유도되는 농약의 엽면 침투성 연구 현황)

  • Yu, Ju-Hyun;Cho, Kwang-Yun;Kim, Jeong-Han
    • The Korean Journal of Pesticide Science
    • /
    • v.6 no.1
    • /
    • pp.16-24
    • /
    • 2002
  • Research trends in the measurement of foliar uptake of pesticides and the recently proposed action mechanism of the surfactant-induced uptake of pesticides were reviewed with the related reports and studies. Major techniques used in those fields are bioassay, radiotracer techniques with leaves or cuticular membrane. Recently, a new method using Congo Red as a tracer was proposed. The limiting factor in the pesticides uptake into leaves is the waxy layer which consists of the epicuticular and cuticular wax. Physico-chemical parameters such as molar volume, water solubility and partition coefficient of pesticides have limited influences on the pesticide uptake into leaves. Polydisperse ethoxylated fatty alcohol surfactants are well known as the good activator for many pesticides. It is now generally agreed that uptake activation is not related to the intrinsic surface active properties of surfactants such as surface activity, solvent property, humectancy and critical micelle concentration. Recent studies using ESR-spectroscopy revealed that the surfactants have an unspecific plasticising effect on the molecular structure of the wax and cuticular matrix, leading to increased mobilities of pesticides. Penetration of surfactants into waxy layer altered the pesticide mobility in wax and the partition coefficient of pesticide, and then the pesticides penetration into leaves was enhanced temporally. The enhancing effect of surfactant could be significantly different depending on the carbon number of aliphatic moiety and the number of ethoxy group in polyoxyethylene chain of surfactants. It is suggested that the rate of penetration of surfactants should have a significant relationship with the rate of penetration of pesticides.

ALL-SKY OBSERVATION OF THE 2001 LEONID METEOR STORM: 1. METEOR MAGNITUDE DISTRIBUTION (전천 카메라를 이용한 2001 사자자리 유성우 관측: 1. 유성 등급 분포)

  • 김정한;정종균;김용하;원영인;천무영;임홍서
    • Journal of Astronomy and Space Sciences
    • /
    • v.20 no.4
    • /
    • pp.283-298
    • /
    • 2003
  • The 2001 Leonid meteor storm has been observed all over the world, and its most intense flux since the last few decades has caused great interest among both laymen and experts. Especially, its maximum hours occurred at dawn hours of Nov. 19 in the east Asia, during which moonless clear night at the Mt. Bohyun allowed us near perfect condition of observation. Observation was carried out in the period of 01:00∼05:40(KST), which include the predicted maximum hours, with all-sky camera installed for upper atmospheric airglow research. Tn this paper we analyze 68 all-sky images obtained in this period, which contain records of 172 meteors. Utilizing the zenith hourly rate(ZHR) of 3000 and magnitude distribution index of 2, which were reported to International Meteor Organization by visible observers in the east Asia, we estimate the limiting magnitude of about 3 for meteors detected in our all-sky images. We then derive magnitudes of 83 meteors with clear pixel brightness outlines among the initially detected 172 meteors by comparing with neighbor standard stars. Angular velocities of meteors needed for computing their passing times over an all-sky image are expressed with a simple formula of an angle between a meteor head and the Leonid radiant point. The derived magnitudes of 83 meteors are in the range of -6∼-1 magnitude, and its distribution shows a maximum new -3mag. The derived magnitudes are much smaller than the limiting magnitude inferred from the comparison with the result of naked-eye observations. The difference may be due to the characteristic difference between nearly instantaneuous naked-eye observations and CCD observations with a long exposure. We redetermine magnitudes of the meteors by adjusting a meteor lasting time to be consistent with the naked-eye observations. The relative distribution of the redetermined magnitudes, which has a maximum at 0 mag., resembles that of the magnitudes determined with the in-principle method. The relative distribution is quite different from ones that decrease monotonically with decreasing magnitudes for meteors(1∼6) sensitive to naked-eye observations. We conclude from the magnitude distribution of our all-sky observation that meteors brighter than about 0 mag., appeared more frequently during the 2001 Leonid maximum hours. The frequent appearance of bright meteors has significantly important implication for meteor research. We noted, however, considerably large uncertainties in magnitudes determined only by comparing standard stars due to the unknown lasting time of meteors and the non-linear sensitivity of all-sky camera.

Effect of Exogenous Hormones on Anthocyanin Accumulation and Phenylalaine Ammonia-lyase and Chalcone-synthase Activity in the Hairy Root Cultures of Raphanus sativus cv. Chungpihongsim (청피홍심무우의 모상근 배양에서 안토시아닌의 생성 및 PAL, CHS의 활성에 미치는 호르몬의 영향)

  • 안준철;백윤웅조혜선황백
    • KSBB Journal
    • /
    • v.9 no.1
    • /
    • pp.26-34
    • /
    • 1994
  • When effects of exogenous hormone on hairy root cultures of Raphanus sativs cv. Chungpihongsim examined, the highest anthocyanin synthesis and disorganization were observed when 2, 4-D was supplemented to the culture medium Cytokinins showed early weak induction after transfer and ABA showed inhibitory effect and GA3 showed no effects in anthocyanin synthesis. Hormones except for 2, 4-D in 1 mg/$\ell$ concentration did not induce disorganization of hairy root and retarded growth of hairy root. Time-course changes in anthocyanin synthesis, phenylalanine ammonia-lyase activity and chalcone synthase activity were examined in culture condition contalning 2, 4-D and kinetin. In a medium containing 2, 4-D, anthocyanin synthesis began to increase on the 9th day and reaching maxima on the 18th day after transfer. Maximum peak of PAL activity appeared on the 3-9th day and another minor peak appeared on the 18th day. CHS activity increased from 9th day, reaching maximum on the 18th day and remained at a relatively high level for culture period. In a medium containing kinetin, anthocyanin synthesis increased temporarily on the 6-9th days, early days after transfer and maintained at a low level for remaining culture period. Peak of PAL activity appeared on the 6th day and CHS activity increased from the 6th days, reaching maxima about 18th day and remained at a relatively high level. In particular, addition of kinetin after preculture in hormone free medium for 2 weeks which was thought of wound healing period showed no effects in anthocyanin synthesis. This results showed that stimulation of anthocyanin synthesis by 2, 4-D and kinetin was meaningfully connected with changes of PAL, CHS activity, and then suggested rate-limiting role of CHS on anthocyanin synthesis in that there is close correlation between anthocyanin synthesis and changes of CHS activity in time-course. Besides, it is considered that cytoklnins involving kinetin stimulated anthocyanin synthesis be due to "wound response" by cutting of young roots, and that difference in time-course peak and PAL, CHS activities expressed by 2, 4-D and kinetin result from occurrence of isozyme which have different regulatory mechanism.mechanism.

  • PDF

Enhanced production of monacolin-K through supplement of monacolin-K precursors into production medium and cloning of SAM synthetase gene (metK) (Precursor제공 및 생합성 관련 유전자의 cloning을 통한 Monacolin-K 생산성 향상)

  • Lee, Mi-Jin;Jeong, Yong-Seob;Chun, Gie-Taek
    • KSBB Journal
    • /
    • v.23 no.6
    • /
    • pp.519-524
    • /
    • 2008
  • Monacolin-K is a strong anti-hypercholesterolemic agent produced by Monascus sp. via polyketide pathway. High-yielding mutants of monacolin-K were developed through rational screening strategies adopted based on understanding of monacolin-K biosynthetic pathway. Through the experiments for investigating various amino acids as putative precursors for the monacolin-K biosynthesis, it was found that production level of monacolin-K was remarkably increased when optimum amount of cysteine was supplemented into the production medium. We suggested that these phenomena might be related to the special roles of SAM (S-adenosyl methionine), a putative methyl group donor in the biosynthetic pathway of monacolin-K, demonstrating close interrelationship between SAM-synthesizing primary metabolism and monacolin-K synthesizing secondary metabolism. Namely, increase in the intracellular amount of SAM derived from the putative precursor, cysteine which was extracellularly supplemented into the production medium might contribute to the significant enhancement in the monacolin-K biosynthetic capability of the highly mutated producers. On the basis of these assumptions derived from the above fermentation results, we decided to construct efficient expression vectors harboring SAM synthetase gene (metK) cloned from A. nidulans, with the hope that increased intracellular level of SAM could lead to further enhancement in the monacolin-K production through overcoming a rate-limiting step associated with monacolin-K biosynthesis. Hence, in order to overcome the plausible rate-limiting step associated with monacolin-K biosynthesis by increasing intracellular level of SAM, we transformed the producer mutants with an efficient expression vector harboring gpdA promoter of the producer microorganism, and metK gene. Notably, from the resulting various transformants, we were able to screen a very high-yielding transformant which showed approximately 3.3 fold higher monacolin-K productivity than the parallel nontransformed mutants in shake flask cultures performed under the identical fermentation conditions.