https://scholarworks.unist.ac.kr/handle/201301/1 2026-05-13T09:01:53Z https://scholarworks.unist.ac.kr/handle/201301/91694 Title: Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy Author(s): Jang, Hyun-Jun; Lee, Yo Han; Tam, Dao; Jo, Yunju; Khim, Keon Woo; Eom, Hye-jin; Lee, Ju Eun; Song, Yi Jin; Choi, Sun Sil; Park, Kieun; Ji, Haneul; Chae, Young Chan; Myung, Kyungjae; Kim, Hongtae; Ryu, Dongryeol; Park, Neung Hwa; Park, Sung Ho; Choi, Jang Hyun Abstract: Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment. 2023-07-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91693 Title: PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III Author(s): Kim, Hye Yun; Lee, Jieun; Kim, Hyun-Jin; Lee, Byeong Eun; Jeong, Jaewook; Cho, Eun Jeong; Jang, Hyun-Jun; Shin, Kyeong Jin; Kim, Min Ji; Chae, Young Chan; Lee, Seung Eun; Myung, Kyungjae; Baik, Ja-Hyun; Suh, Pann-Ghill; Kim, Jae-Ick Abstract: Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III. 2023-10-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91648 Title: Heteroresistance to amikacin in Klebsiella aerogenes isolates from patients in an intensive care unit in Brazil Author(s): Crispim, Natalia Ribeiro; Nunes, Gustavo Dantas; Soares, Gabriela Guerrera; Shilling, Rebecca Elizabeth; Ferreira, Roumayne Lopes; Campos, Leslie Camelo; Alcobaca, Olinda Soares Athaide; da Silva, Joao Pedro Maia de Oliveira; Rodrigues, Saulo Henrique; Pitondo-Silva, Andre; Fuentes, Andrea Soares da Costa; da Cunha, Anderson Ferreira; Mitchell, Robert J.; Pranchevicius, Maria-Cristina da Silva Abstract: Heteroresistance is defined by the presence of subpopulations within a bacterial isolate that exhibit greater antibiotic resistance than the dominant population. In this study, we investigated amikacin heteroresistance in the opportunistic, nosocomial pathogen Klebsiella aerogenes (AHR-KA). Eight carbapenemase-resistant, but amikacin-susceptible, isolates from intensive care units of a Brazilian hospital were analyzed. Population analysis profiling identified five amikacin heteroresistant isolates (AHR-KA-1 to 5), with subpopulation frequencies ranging from 1.83 & times; 10-7 to 6.01 & times; 10-6. Among these, only AHR-KA-1 exhibited stable heteroresistance following serial passaging in antibiotic-free media. AHR-KA-1 demonstrated only slightly reduced growth rates when compared with those of the unstable AHR-KAs, parental, and control strains, suggesting no significant fitness cost associated with drug resistance. Time-kill assays for AHR-KA-1 showed an initial decline in cell viability, followed by regrowth at both 4 & times; and 8 & times; MIC. The draft genome of the stable isolate had a total length and G+C content similar to most of the sequenced genomes from K. aerogenes. Notably, AHR-KA-1 ' s aac(6 ')-Ib-cr variant contained D179Y and R102W mutations, conferring amikacin resistance. Moreover, quantitative reverse transcription PCR revealed significantly elevated expression of the aac(6 ')-Ib-cr gene in AHR-KA-1 before amikacin-free passage, compared to both the parental strain and the AHR-KA-1 strain after drug-free passage. Therefore, this study identified amikacin heteroresistance in carbapenemase-producing K. aerogenes, including a stable, mutation-driven phenotype with low fitness cost and rapid regrowth under high amikacin concentrations, underscoring its clinical relevance. These findings reinforce the importance of detecting heteroresistant subpopulations and strengthening surveillance to prevent treatment failure and the spread of undetected resistance.IMPORTANCEKlebsiella aerogenes, an opportunistic human pathogen, is frequently implicated in severe and invasive infections, particularly in immunocompromised individuals. The growing prevalence of antibiotic resistance among these strains poses a significant therapeutic challenge. The phenomenon of heteroresistance further complicates management, potentially leading to diagnostic difficulties due to the lack of standardized detection methods and subsequent treatment failures. Our studies identified and characterized K. aerogenes strains heteroresistant to amikacin, isolated from patients in an intensive care unit. Such data can serve as a foundational reference for understanding the clinical relevance, genomic variability, and pathogenic potential of K. aerogenes heteroresistance to antibiotics used in clinical settings. 2026-03-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91646 Title: Redefining nucleotide-binding oligomerization domain-like receptors: from immune sentinels to multifunctional regulators Author(s): Kim, Suhyun; Park, Sehee; Lee, SangJoon Abstract: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a large family of intracellular pattern recognition receptors primarily involved in innate immunity. Although canonical inflammasome-forming NLRs, such as NLRP3 and NLRC4, and microbial sensors, including NOD1 and NOD2, are well characterized, the functions of many other NLRs remain poorly understood. This review addresses this gap by highlighting the critical, context-dependent roles of these less-characterized NLRs beyond pathogen sensing. Here, we classify these NLRs as immune modulators, regulators of autophagy and mitophagy, tissue-specific effectors, and reproductive mediators, expanding the traditional view of NLR functions. Understanding the diverse, context-dependent roles of NLRs across biological systems is essential to fully understand their complex regulatory networks and therapeutic potential, which extends beyond classical inflammasome functions. 2026-02-28T15:00:00Z