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Applicability of KEAP1 E3 Ligase to the PROTAC Platform
Raju Gurung(Raju Gurung),Jae Rim Lee(Jae Rim Lee),Min Ju Cho(Min Ju Cho),Jin Ah Jeong(Jin Ah Jeong),Sung Jean Park(Sung Jean Park),Kwang Won Jeong(Kwang Won Jeong),Dongyun Shin(Dongyun Shin) 대한약학회 2024 약학회지 Vol.68 No.4
Proteolysis-targeting chimeras (PROTACs) represent an innovative approach for drug design involving the creation of a heterobifunctional molecule. This molecule uses an E3 ligase to target and degrade specific proteins via the ubiquitin-proteasome system (UPS). The three essential components of PROTAC are a ligand for the protein of interest (POI), a binder to recruit an E3 ligase, and a linker connecting these two elements. Given the relatively large number of E3 ligases in the human body (>600), only a few such as VHL, CRBN, MDM2, cIAP1, DCAF15, RNF4, and RNF114 have been used in existing PROTACs. PROTACs facilitate degradation of pathological proteins through the UPS pathway. Consequently, the identification of a broad range of E3 ligase recruiters is crucial for advancing targeted protein degradation (TPD) strategies. In this study, we focused on designing KEAP1 binder PROTACs, using a selective, potent small-molecule inhibitor of KEAP1 as an E3 ligase recruiter. It was linked to JQ1 (a POI ligand) via a flexible aliphatic linker. Our compound SD-2406, with KEAP1 E3 ligase recruiter, effectively degraded BRD4 target proteins in LNCaP cells. This demonstrates the potential of expanding the E3 ligase toolbox for the development of PROTAC technology.
Anup Gurung,Om Prakash Gurung,Sang-Eun Oh 강원대학교 환경연구소 2010 Journal of the Environment Vol.7 No.-
Agriculture and animal husbandry are important livelihood strategies for a large proportion of the poor rural households in developing countries. However, in recent years, the process of migration has become a major feature of diversification for many rural societies. This paper explores the triangular relationship among agricultural productivity, pastoralism, and rural out-migration by presenting a case study from the trans-Himalayan regions in Nepal. The general findings of the study revealed that rural out-migration affects the responsibilities and tasks among the rural households significantly. The majority of the households diversify their income sources by involving in labor migration both internally and internationally. However, the massive exodus of people has left its toll on the villages. Substantial proportions of agricultural land were abandoned in Sikles and Tangting that ultimately reduced agricultural output significantly in the villages. In addition, animal husbandry, one of the important livelihood strategies in the village is also on the verge of declining. In Sikles, the numbers of livestock including sheep, goats, buffaloes, and cows/oxen decreased by 81.66%, 77.77%, 88.88%, and 88%, respectively. Similarly, in Tangting also, the numbers of sheep, goats, buffaloes, and cows/oxen decreased by 90%, 96.66%, 91.66%, and 95%, respectively. Nevertheless, from the socio-economic point of view, migration is becoming integral part of life for the villagers yet since remittances usually exceed the expenses for hiring additional workforce for agriculture and pastoralism; most people consider migration is profitable and complementary livelihood strategies in the villages.
지역 생계에 미치는 외주이동 노동의 영향: 네팔을 중심으로
구룽아누프 ( A. Gurung ),구룽옴프라카스 ( O. P. Gurung ),오상은 ( S. E. Oh ) 강원대학교 농업생명과학연구원(구 농업과학연구소) 2011 강원 농업생명환경연구 Vol.23 No.1
Migration is one of the historically existing phenomena in Nepal. Over the past two decades, labor migration and remittances are major economic mainstays for Nepal`s economy. In 2009, approximately 2.98 billion USD was remitted to Nepal from international migrants, which accounted for 21.8% of national gross domestic product. This study empirically evaluates a conceptual framework incorporating rural household livelihoods as an integrative mediating factor between rural migration and the rural economic development in the context of labor out-migration in Namarjung Village Development Committee, one of the underprivileged rural communities in Nepal. The analysis draws on data collected through in-depth household questionnaire survey, key informant interviews, and focus group discussion to estimate the hypothesized effects. Results confirm the hypothesis that migrant and non-migrant households differ significantly in livelihood activities including agricultural production, income and consumption behaviors, and resource use and land management. It was found that households annual income increased significantly (24%, 50,000 NPR/year) after involvement in the abroad employment. In very recent years, higher percentage of female (25.56%) was also found involving in international migration. Nevertheless, it was found that the process of migration affected the human capital negatively and has created shortage of manpower which corresponds to 51%. Additionally, the livestock, mainly goat and sheep also reduced by 50%. However, it was found that with increasing return inflows of remittances, the social and physical facilities and services near to the surveyed area also improved substantially including access to electricity, transportation, schools, health clinics, and communicating media. This study reveals that the often countervailing nature of out-migration affects the short and long terms rural community revitalization processes.
Gurung, Mamata,Tamang, Migma Dorji,Moon, Dong Chan,Kim, Su-Ran,Jeong, Jin-Ha,Jang, Geum-Chan,Jung, Suk-Chan,Park, Yong-Ho,Lim, Suk-Kyung American Society for Microbiology 2015 Journal of clinical microbiology Vol.53 No.7
<P>Characterization of 227 <I>Streptococcus suis</I> strains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to the <I>tet</I> gene, <I>erm</I>(B), <I>erm</I>(C), <I>mph</I>(C), and <I>mef</I>(A) and/or <I>mef</I>(E) genes, <I>aph(3′)-IIIa</I> and <I>aac(6′)-Ie-aph(2″)-Ia</I> genes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively.</P>
Gurung, Anup,Kim, Jungrae,Jung, Sokhee,Jeon, Byong-Hun,Yang, Jae E,Oh, Sang-Eun Kluwer Academic Publishers 2012 Biotechnology letters Vol.34 No.10
<P>Stacking of microbial fuel cells (MFC) by connecting multiple small-sized units in a series is used for generating higher power from the MFCs. However, voltage reversal is a critical problem in a serially connected MFC unit. The voltage reversal often occurs when substrate concentration is relatively low in the anodic compartment. Two rectangular individual cells were stacked together in series: MFC1 was fed with 1 g glucose L(-1) throughout the experiment while MFC2 was fed with various concentrations of glucose (0.1, 0.2, 0.3, 0.5 and 0.8 g L(-1)). Voltage reversal occurred when the stack configuration was performed using (1 + 0.1) g glucose L(-1). The stacked configurations with (1 + 0.2, 1 + 0.3, 1 + 0.5 and 1 + 0.8) g glucose L(-1) were operated successfully without the voltage reversal. The maximum powers of 1.88, 2.04, 3.6, 2.5 and 2.18 mW were obtained with the stacked configurations of (1 + 0.2), (1 + 0.3), (1 + 0.5), (1 + 0.8) and (1 + 1) g glucose L(-1), respectively. Except in the stacked configuration with (1 + 0.1) g glucose L(-1), the stacked voltages obtained were similar.</P>
Gurung, D. B.,Saxena, V. P.,Adhikary, P. R. The Korean Society for Computational and Applied M 2009 Journal of applied mathematics & informatics Vol.27 No.1
This paper presents a Finite Element Method (FEM) application to thermal study of natural three layers of human dermal parts of varying properties. This paper carries out investigation of temperature distributions in these layers namely epidermis, dermis and under lying tissue layer. It is assumed that the outer skin is exposed to atmosphere and the loss of heat due to convection, radiation and evaporation of water have also been taken into account. The computations are carried out for one dimensional unsteady state case and the shape functions in dermal parts have been considered to be quadratic. A Finite Element scheme that uses the Crank-Nicolson method is used to solve the problem and the results computed have been exhibited graphically.
Prevalence and antimicrobial susceptibility of Acinetobacter from raw bulk tank milk in Korea
Gurung, M.,Nam, H.M.,Tamang, M.D.,Chae, M.H.,Jang, G.C.,Jung, S.C.,Lim, S.K. American Dairy Science Association 2013 Journal of dairy science Vol.96 No.4
The objective of this study was to determine the prevalence of Acinetobacter spp. in bulk tank milk (BTM) samples from different provinces of Korea and to analyze their antimicrobial susceptibility. Altogether, 2,287 BTM samples were investigated. Among them, Acinetobacter spp. were isolated from 176 BTM samples. Out of 176 Acinetobacter spp., 57 isolates were identified as Acinetobacter baumannii. None of the isolates were resistant to cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, or colistin. Resistance to amikacin, gentamicin, piperacillin, and cefotaxime was 2.3, 7.4, 2.3, and 4.0%, respectively. Acinetobacter spp. were least susceptible to tetracycline (17.6%), followed by trimethoprim-sulfamethoxazole (15.9%), ceftazidime (10.8%), and ampicillin-sulbactam (10.2%). Overall, A. baumannii strains were susceptible to most of the antimicrobial agents tested compared with other Acinetobacter spp. The Acinetobacter isolates showed 17 different patterns of antimicrobial resistance. The most frequent resistance profile observed was ampicillin-sulbactam (n=13), followed by tetracycline (n=9), ceftazidime-tetracycline (n=8), and trimethoprim-sulfamethoxazole-tetracycline (n=8). The results of this study confirmed that Acinetobacter, including A. baumannii strains, are present in BTM, which clearly showed the importance of examining BTM not only for foodborne pathogens but also for Acinetobacter spp., which could be of public health concern. To the best of our knowledge, this is the first report of Acinetobacter spp. in BTM samples from Korea.