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nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology
Lee, Sang-Eun,Kim, Yoonju,Han, Jeong-Kyu,Park, Hoyong,Lee, Unghwi,Na, Myeongsu,Jeong, Soomin,Chung, ChiHye,Cestra, Gianluca,Chang, Sunghoe National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.24
<P>Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that directly interacts with synapseassociated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3), a postsynaptic scaffolding protein critical for the assembly of glutamatergic synapses. Although genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behaviors resembling many aspects of symptoms in patients with bipolar disorder, the actual function of nArgBP2 at the synapse is completely unknown. Here, we found that the knockdown (KD) of nArgBP2 by specific small hairpin RNAs (shRNAs) resulted in a dramatic change in dendritic spine morphology. Reintroducing shRNA-resistant nArgBP2 reversed these defects. In particular, nArgBP2 KD impaired spinesynapse formation such that excitatory synapses terminated mostly at dendritic shafts instead of spine heads in spiny neurons, although inhibitory synapse formation was not affected. nArgBP2 KD further caused a marked increase of actin cytoskeleton dynamics in spines, which was associated with increased Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1)/p21-activated kinase (PAK) phosphorylation and reduced activity of cofilin. These effects of nArgBP2 KD in spines were rescued by inhibiting PAK or activating cofilin combined with sequestration of WAVE. Together, our results suggest that nArgBP2 functions to regulate spine morphogenesis and subsequent spine-synapse formation at glutamatergic synapses. They also raise the possibility that the aberrant regulation of synaptic actin filaments caused by reduced nArgBP2 expression may contribute to the manifestation of the synaptic dysfunction observed in manic/bipolar disorder.</P>
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Hoyong Kim,Yong Kuk Park,Jae-Kon Lee,Dong-RyuI Lee,Gi Dae Kim 한국자동차공학회 2000 한국 자동차공학회논문집 Vol.8 No.6
A MIMO model reference control scheme incorporating the variable structure theory for a vehicle four wheel steering system(4WS) is proposed and evaluated for a class of continuous-time nonlinear dynamics with known or unknown uncertainties. The scheme employs a neural network to identify the plant systems, where the neural network estimates the nonlinear dynamics of the plant. By the Lyapunov direct method, the algorithm is proven to be globally stable, with tracking errors converging to the neighborhood of zero. The merits of this scheme is that the global system stability is guaranteed and it is not necessary to know the exact structure of the system. With the resulting identification model which contains the neural networks, it does not need higher degrees of freedom vehicle model than 3 degree of freedom model. The proposed scheme is applied to the active four wheel system and shows the validity and effectiveness of simulation. The nonlinear three-degree-of freedom vehicle handling model is used to investigate vehicle handling performances. In simulation of the J-turn maneuver, the reduction of yaw rate overshoot of a typical mid-size car improved by 30% compared to a two wheel steering system(2WS) case, resulting that the proposed scheme gives faster yaw rate response and smaller side slip angle than the 2WS case.
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Lee Hye Young,Kwon Yunhyung,Lee Sang Eun,Kim Jieun,Choi Hoyong 질병관리청 2024 Osong Public Health and Research Persptectives Vol.15 No.3
Objectives: Between July 2, 2021, and September 20, 2022, a Mycobacterium bovis outbreak occurred among exhibition animals at a zoo in the Republic of Korea. This study was conducted to assess the likelihood of M. bovis transmission to human contacts through a contact investigation and to implement preventive treatment for latent tuberculosis infection (LTBI).Methods: In this descriptive study, the Korea Disease Control and Prevention Agency conducted a contact investigation, which included interviews, interferon-gamma release assay (IGRA) tests, and chest X-rays. Contacts underwent IGRA testing on 2 occasions: initial testing of 29 contacts (15 in the first cluster of infection and 14 in the second cluster) and follow-up testing of the 15 contacts in the first cluster.Results: The study included 29 participants, 18 of whom were male (62.1%) and 11 female (37.9%). The mean participant age was 37.3 years (standard deviation, 9.6 years). In the initial IGRA tests, 6 of the 29 participants tested positive, indicating a prevalence of 20.7%. Following prolonged exposure, 1 additional positive case was detected in follow-up testing, raising the prevalence of LTBI to 24.1%. None of the contacts had active tuberculosis. Among the 7 individuals with positive results, 2 (28.6%) underwent treatment for LTBI.Conclusion: This study faced challenges in confirming the transmission of M. bovis infection from infected animals to humans in the Republic of Korea. Nevertheless, adopting a One Health approach necessitates the implementation of surveillance systems and infection control protocols, particularly for occupational groups at high risk of exposure.
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Lee, Junghun,Jung, Hoyong,Kim, Minjung,Lee, Eunkyu,Im, Daseul,Aman, Waqar,Hah, Jung-Mi Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.8
<P><B>Abstract</B></P> <P>A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (<B>8a</B>–<B>8i</B>, <B>9a</B>–<B>9m</B>) and urea (<B>10a</B>–<B>10d</B>, <B>11a</B>–<B>11d</B>) with diverse hydrophobic moieties. One of the most potent inhibitor <B>10d</B>, 1-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-2,3-dihydro-<I>1H</I>-thieno [3,4-<I>b</I>][1,4]diazepin-4-yl)phenyl)urea was found to be very potent inhibitor of multi-protein kinases including FMS kinase (IC<SUB>50</SUB> = 3.73 nM) and is a promising candidate for further development in therapeutics for cancer.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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