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Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors
Lim, Sungsu,Haque, Md. Mamunul,Nam, Ghilsoo,Ryoo, Nayeon,Rhim, Hyewhon,Kim, Yun Kyung MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.9
<P>Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with <I>O</I>-linked β-<I>N</I>-acetylglucosamine (<I>O</I>-GlcNAc) in normal brain. In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. Despite the importance of <I>O</I>-GlcNAcylation in tau pathology, <I>O</I>-GlcNAc transferase (OGT), and an enzyme catalyzing <I>O</I>-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of <I>O</I>-GlcNAcase (OGA). Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology.</P>
Lim, Sungsu,Haque, Md. Mamunul,Su, Dongdong,Kim, Dohee,Lee, Jun-Seok,Chang, Young-Tae,Kim, Yun Kyung unknown 2017 Chemical communications Vol. No.
<▼1><P>As a cell-permeable imaging probe, BD-tau selectively labeled pathological tau aggregates in live neuronal cells.</P></▼1><▼2><P>Neuronal accumulation of tau aggregates is a pathological hallmark in multiple neurodegenerative disorders, collectively called tauopathies. A tau aggregation sensor that can monitor abnormal tau aggregation in neurons would facilitate the study of tau aggregation processes and the discovery of tau aggregation blockers. Here, we describe a BODIPY-fluorescence sensor (BD-tau) that selectively responds to pathological tau aggregates in live cells.</P></▼2>
Stability of the Max-Weight Protocol in Adversarial Wireless Networks
Sungsu Lim,Kyomin Jung,Andrews, Matthew IEEE 2014 IEEE/ACM transactions on networking Vol.22 No.6
<P>In this paper, we consider the Max-Weight protocol for routing and scheduling in wireless networks under an adversarial model. This protocol has received a significant amount of attention dating back to the papers of Tassiulas and Ephremides. In particular, this protocol is known to be throughput-optimal whenever the traffic patterns and propagation conditions are governed by a stationary stochastic process. However, the standard proof of throughput optimality (which is based on the negative drift of a quadratic potential function) does not hold when the traffic patterns and the edge capacity changes over time are governed by an arbitrary adversarial process. Such an environment appears frequently in many practical wireless scenarios when the assumption that channel conditions are governed by a stationary stochastic process does not readily apply. In this paper, we prove that even in the above adversarial setting, the Max-Weight protocol keeps the queues in the network stable (i.e., keeps the queue sizes bounded) whenever this is feasible by some routing and scheduling algorithm. However, the proof is somewhat more complex than the negative potential drift argument that applied in the stationary case. Our proof holds for any arbitrary interference relationships among edges. We also prove the same stability of ε-approximate Max-Weight under the adversarial model. We conclude the paper with a discussion of queue sizes in the adversarial model as well as a set of simulation results.</P>
Lim Sungsu,Shin Seulgi,Sung Yoonsik,Lee Ha Eun,Kim Kyu Hyeon,Song Ji Yeon,Lee Gwan-Ho,Aziz Hira,Lukianenko Nataliia,Kang Dong Min,Boesen Nicolette,Jeong Hyeanjeong,Abdildinova Aizhan,Lee Junghee,Yu By 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer’s disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. 14C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan disassembles tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents methylene blue and LMTM failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued cognitive declines induced by tauopathy in the TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.
VMware Workstation 가상 머신 이미지에 대한 디지털 포렌식 조사 절차 및 손상된 이미지 복구 방안
임성수(Sungsu Lim),유병영(Byeongyeong Yoo),박정흠(Jungheum Park),변근덕(KeunDuck Byun),이상진(Sangjin Lee) 한국정보보호학회 2011 정보보호학회논문지 Vol.21 No.2
가상화는 논리적인 가상환경으로 하드웨어의 물리적인 한계를 극복하기 위한 기술이다. 최근 비용 절감 및 그린 IT 정책의 일환으로 가상화 환경을 도입하는 기업들이 증가하는 추세이다. 특히 데스크톱 가상화는 한 대의 물리적 컴퓨터에서 다양한 운영체제를 효율적으로 사용할 수 있기 때문에 가장 활발하게 사용되는 기술유형 중 하나이다. 가상화 기술의 핵심 요소인 가상 머신 이미지는 하드 디스크 이미지와 구조적으로 다르기 때문에 조사에 어려움이 있다. 따라서 가상 머신에 대한 기술적 이해를 바탕으로 가상 머신 이미지에 적합한 조사 절차 및 방안에 대한 연구가 필요하다. 본 연구는 가장 많은 사용자를 가지고 있는 VMware Workstation 가상 머신 이미지에 대한 디지털 증거 조사 절차와 손상된 이미지에 대한 조사 방안을 제안한다. Virtualization is a technology that uses a logical environment to overcome physical limitations in hardware. As a part of cost savings and green IT policies, there is a tendency in which recent businesses increase the adoption of such virtualization. In particular, regarding the virtualization in desktop, it is one of the most widely used technology at the present time. Because it is able to efficiently use various types of operating systems in a physical computer. A virtual machine image that is a key component of virtualization is difficult to investigate. because the structure of virtual machine image is different from hard disk image. Therefore, we need researches about appropriate investigation procedure and method based on technical understanding of a virtual machine. In this research, we suggest a procedure of investigation on a virtual machine image and a method for a corrupted image of the VMware Workstation that has the largest number of users.