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Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes.
Kim, Jinyoung,Cheon, Hwanju,Jeong, Yeon Taek,Quan, Wenying,Kim, Kook Hwan,Cho, Jae Min,Lim, Yu-Mi,Oh, Seung Hoon,Jin, Sang-Man,Kim, Jae Hyeon,Lee, Moon-Kyu,Kim, Sunshin,Komatsu, Masaaki,Kang, Sang-Woo American Society for Clinical Investigation 2014 The Journal of clinical investigation Vol.124 No.8
<P>Islet amyloid accumulation is a hallmark of human type 2 diabetes (T2D). In contrast to human islet amyloid polypeptide (hIAPP), murine islet amyloid polypeptide (mIAPP) does not exhibit amyloidogenic propensity. Because autophagy is important in the clearance of amyloid-like proteins, we studied transgenic mice with β cell-specific expression of hIAPP to evaluate the contribution of autophagy in T2D-associated accumulation of hIAPP. In mice with β cell-specific expression of hIAPP, a deficiency in autophagy resulted in development of overt diabetes, which was not observed in mice expressing hIAPP alone or lacking autophagy alone. Furthermore, lack of autophagy in hIAPP-expressing animals resulted in hIAPP oligomer and amyloid accumulation in pancreatic islets, leading to increased death and decreased mass of β cells. Expression of hIAPP in purified monkey islet cells or a murine β cell line resulted in pro-hIAPP dimer formation, while dimer formation was absent or reduced dramatically in cells expressing either nonamyloidogenic mIAPP or nonfibrillar mutant hIAPP. In autophagy-deficient cells, accumulation of pro-hIAPP dimers increased markedly, and pro-hIAPP trimers were detected in the detergent-insoluble fraction. Enhancement of autophagy improved the metabolic profile of hIAPP-expressing mice fed a high-fat diet. These results suggest that autophagy promotes clearance of amyloidogenic hIAPP, autophagy deficiency exacerbates pathogenesis of human T2D, and autophagy enhancers have therapeutic potential for islet amyloid accumulation-associated human T2D.</P>
Converting a Host Receptor into Sustained Intranasal Virucides against SARS-CoV-2 Using Nanodiscs
Jaehyeon HWANG,Wonbeom PARK,Soomin KIM,SeungJoo KIM,Suhyun KIM,Nayoon CHOI,Eunkhang PARK,Hwanju KIM,Mina KIM,Hyunjoo CHOO,Soyun CHOI,MinKyeom KIM,YeonJin CHO,Dae-Hyuk KWEON 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10
Virtual Snooping Coherence for Multi-Core Virtualized Systems
Daehoon Kim,Chang Hyun Park,Hwanju Kim,Jaehyuk Huh IEEE 2016 IEEE transactions on parallel and distributed syst Vol.27 No.7
<P>Proliferation of virtualized systems opens a new opportunity to improve the scalability of multi-core architectures. Among the scalability bottlenecks in multi-cores, cache coherence has been one of the most critical problems. Although snoop-based protocols have been dominating commercial multi-core designs, it has been difficult to scale them for more cores, as snooping protocols require high network bandwidth and power consumption for snooping all the caches. In this paper, we propose a novel snoop-based cache coherence protocol, called virtual snooping, for virtualized multi-core architectures. Virtual snooping exploits memory isolation across virtual machines and prevents unnecessary snoop requests from crossing the virtual machine boundaries. Each virtual machine becomes a virtual snoop domain, consisting of a subset of the cores in a system. Although the majority of virtual machine memory is isolated, sharing of cachelines across VMs still occur. To address such data sharing, this paper investigates three factors, data sharing through the hypervisor, virtual machine relocation, and content-based sharing. In this paper, we explore the design space of virtual snooping with experiments on emulated and real virtualized systems including the mechanisms and overheads of the hypervisor. In addition, the paper discusses the scheduling impact on the effectiveness of virtual snooping.</P>