339 research outputs found

    Fear conditioning occludes late-phase long-term potentiation at thalamic input synapses onto the lateral amygdala in rat brain slices

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    Late-phase long-term potentiation (L-LTP) of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala (T-LA synapses) has been proposed as a cellular substrate for long-term fear memory. This notion is evidenced primarily by previous reports in which the same pharmacological treatments block both T-LA L-LTP and the consolidation of fear memory. In this study, we report that fear conditioning occludes L-LTP at T-LA synapses in brain slices prepared after fear memory consolidation. L-LTP was restored either when synaptic depotentiation was induced prior to L-LTP induction in brain slices prepared from conditioned rats or when brain slices were prepared from conditioned rats that had been exposed to subsequent fear extinction, which is a behavior paradigm known to induce in vivo synaptic depotentiation at T-LA synapses. These results suggest that fear conditioning recruits L-LTP-like mechanisms that are reversible and saturable at T-LA synapses. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions

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    Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. © 2019, The Author(s).1

    COX-2 regulates the insulin-like growth factor I-induced potentiation of Zn2+-toxicity in primary cortical culture

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    The pretreatment of cultured cortical neurons with neurotrophic factors markedly potentiates the cytotoxicity induced by low concentrations of Zn2+ or excitotoxins. In the current study, we investigated the mechanism underlying the insulin-like growth factor-I (IGF-I)-induced Zn2+ toxicity potentiation. The pretreatment of primary cortical cultures for more than 12 h with 100 ng/ml of IGF-I increased the cytotoxicity induced by 80 muM Zn2+ by more than 2-fold. The IGF-I-enhanced cell death was blocked by the COX-2-specific inhibitors N-[2-(cyclohexyloxyl)-4-nitrophenyl]methane sulfonamide (NS-398; 10-100 muM) and 1-[(4-methylsulfonyl)phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl]pyrazole (SC58125; 10 muM) and by the antioxidant trolox (30 muM). In addition, it was observed that COX-2 expression was increased 12 to 24 h after IGF-I treatment. Preincubation of cortical cultures with IGF-I increased arachidonic acid (AA)-induced cytotoxicity, and AA increased Zn2+ toxicity, which suggested the involvement of COX activity in these cellular responses. Moreover, enhanced COX-2 activity led to a decrease in the cell's reducing power, as indicated by a gradual depletion of intracellular GSH. Cortical neurons pretreated with IGF-I and then Zn2+ showed consistently enhanced reactive oxygen species production, which was repressed by NS-398 and SC58125. Cortical neurons treated with Zn2+ and then AA displayed the increased ROS production, which was also suppressed by NS-398 and SC58125. These results suggest that COX-2 is an endogenous factor responsible for the IGF-I-induced potentiation of Zn2+ toxicity and that enhanced COX-2 activity leads to a decrease in the cell's reducing power and an increase in ROS accumulation in primary cortical cultures

    Notch interferes with the scaffold function of JNK-interacting protein 1 to inhibit the JNK signaling pathway

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    The transmembrane protein Notch is cleaved by gamma-secretase to yield an active form, Notch intracellular domain (Notch-IC), in response to the binding of ligands, such as Jagged. Notch-IC contributes to the regulation of a variety of cellular events, including cell fate determination during embryonic development as well as cell growth, differentiation, and survival. We now show that Notch1-IC suppresses the scaffold activity of c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1) in the JNK signaling pathway. Notch1-IC physically associated with the JNK binding domain of JlP1 and thereby interfered with the interaction between JlP1 and JNK. JlP1 mediated the activation of JNK1 induced by glucose deprivation in mouse embryonic fibroblasts, and ectopic expression of Notch1-IC inhibited JNK activation and apoptosis triggered by glucose deprivation. Taken together, these findings suggest that Notch1-IC negatively regulates the JNK pathway by disrupting the scaffold function of JIP1

    Metal nanoparticles decorated PET/PET-TiO2 bi-component filaments by photocatalytic deposition

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    Gold, silver, and platinum nanoparticles were immobilized on the surface of TiO2 in the sheath part of bi-component filaments. The processes involved include the spinning process used to prepare polyethylene terephthalate (PET)/PET-TiO2 bi-component filaments and the photocatalytic deposition process of gold, silver and platinum nanoparticles. The core part and the sheath part consist of virgin PET and 4 wt.% of TiO2 compounded PET, respectively. The sheath: core ratio of the filament was 50:50. For the photo-deposition of metal nanoparticles, adsorption of the metal ions on the surface of the fabrics was performed by immersing them in AgNO3, HAuCl4, and H2PtCl6 aqueous solutions, with simultaneous addition of methanol as a sacrificial agent. Photo-deposition was then carried out under UV light with an irradiation time of 60 seconds. The structural and antibacterial properties of the bi-component filaments were characterized. The nano-sized noble metal particles in a polka dot form were observed around the surface of the TiO2 particles in sheath region of bi-component filaments after photocatalytic deposition. Ag, Au, and Pt metal photo-deposited fabrics showed excellent antimicrobial effect against the two types of bacteria Staphylococcus aureus and Klebsiella pneumoniae under dark conditions. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

    Integration of a rehabilitation robotic system (KARES II) with human-friendly man-machine interaction units

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    In this paper, we report some important results of design and evaluation of a wheelchair-based robotic arm system, named as KARES II (KAIST Rehabilitation Engineering Service System II), which is newly developed for the disabled. KARES II is designed in consideration of surveyed necessary tasks for the target users ( that is, people with spinal cord injury). At first, we predefined twelve important tasks according to extensive interviews and questionnaires. Next, based on these tasks, all subsystems are designed, simulated and developed. A robotic arm with active compliance and intelligent visual servoing capability is developed by using cable-driven mechanism. Various kinds of human-robot interfaces are developed to provide broad range of services according to the levels of disability. Eye-mouse, shoulder/head interface, EMG signal-based control subsystems are used for this purpose. Besides, we describe the process of integration of our rehabilitation robotic system KARES II, and discuss about user trials. A mobile platform and a wheelchair platform are two main platforms in which various subsystems are installed. For a real-world application of KARES II system, we have performed user trials with six selected potential end-users ( with spinal cord injury).This work is fully supported by the Ministry of Science and Technology of Korea as a part of Critical Technology 21 Program on “Development of Intelligent Human-Robot Interaction Technology.” We also like to acknowledge various forms of support from Dr. Byung-Sik Kim and his staff of National Rehabilitation Center, Korea

    A Cooperative Protocol for Vehicle Merging Using Bi-dimensional Artificial Potential Fields

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    In recent years, platooning solutions like cooperative adaptive cruise control (CACC) have been deeply studied. It is common in such platooning literature to assume that the vehicles drive on the same lane (longitudinal platooning). At the same time, lateral control during merging maneuvers is commonly addressed as a path planning problem, in which the ego vehicle changes the lane during merging without necessarily cooperating with its neighboring vehicles (i.e. without considering gap closing). The primary objective of this article is to develop a control strategy which involves both longitudinal and lateral vehicle dynamics, where the vehicles merge and form a platoon in a cooperative way without a priori path planning. Appropriately designed bi-dimensional artificial potential fields are used to achieve this goal and the proposed protocol is verified through simulations with CarSim.Accepted Author ManuscriptTeam Bart De Schutte

    韩偓《香奁集》里的忠君情感 = Patriotic sentiments in Han Wo‘s “Xiang Lian Ji”

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    韩偓《香奁集》是一部艳情诗歌集,在当时的封建社会中找不到应有的地位,并受排挤。许多学者甚至为了维护韩偓“一代忠臣”的身份,想方设法考证《香奁集》非韩偓所作,但屡战屡败。有些学者却认为晚唐文化风流薮泽,韩偓也腐朽其中,但无实证。清代学者震钧认为《香奁集》别有寄托,可见其忠君爱国,把韩偓比作屈原;将《香奁集》比作《离骚》、《九歌》。这种想法却遭后人质疑,认为震钧的论点牵强。笔者认为震钧的观点不无道理,《香奁集》确实有忠君爱国之情,并非无中生有,解读中体味其意,认同震钧之见,并在此篇论文加以发扬与诠释。笔者将梳理韩偓的忠君表现,并通过细读韩偓的香奁诗篇以及学者的相关论文,结合晚唐五代的语境,研究并统计韩偓的修辞手法与整体的情感基调,最后将其诗篇作了具体的分析与解读。Han Wo's "Xiang Lian Ji" is a collection of Erotic poetries. In the feudal society, there is absolutely no room to accommodate romantic poetry and is subjected to exclusion. Many researchers have tried to protect his identity as a loyal officials by trying to find evidences to justify that he did not author "Xiang Lian Ji", but did not succeed. Some researchers think that Han Wo has immersed into the Late Tangs' culture of visiting brothels, however there was not any evidence to support. Qing researcher, Zhen Jun commented that Han Wo wrote "Xiang Lian Ji" to entrust his loyalty for his country and emperor, and further compared Han Wo to Qu Yuan, "Xiang Lian Ji" to "Li Sao" and "Jiu Ge", this was later met with revolts from many researchers. The author agrees with Zhen Jun’s view and has written this thesis to further elaborate on this thinking. First, the author will consolidate his patriotic evidences and with in depth reading of Han Wo’s poetries and related journals and articles of Han Wo, further enhanced by contextualizing Han Wo’s poetries along with the context of late Tang and Five dynasties, elaborates and analyses the rhetorical and emotions frequently appeared in Han Wo's poems, lastly specific analysis and interpretation of Han Wo's "Xiang Lian" poems.Bachelor of Art

    Enhanced mRNA FISH with compact quantum dots

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    Fluorescence in situ hybridization (FISH) is the primary technology used to image and count mRNA in single cells, but applications of the technique are limited by photophysical shortcomings of organic dyes. Inorganic quantum dots (QDs) can overcome these problems but years of development have not yielded viable QD-FISH probes. Here we report that macromolecular size thresholds limit mRNA labeling in cells, and that a new generation of compact QDs produces accurate mRNA counts. Compared with dyes, compact QD probes provide exceptional photostability and more robust transcript quantification due to enhanced brightness. New spectrally engineered QDs also allow quantification of multiple distinct mRNA transcripts at the single-molecule level in individual cells. We expect that QD-FISH will particularly benefit high-resolution gene expression studies in three dimensional biological specimens for which quantification and multiplexing are major challenges. © 2018, The Author(s).1
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