• Title/Summary/Keyword: Salient region

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Targeting the epitope spreader Pep19 by naïve human CD45RA+ regulatory T cells dictates a distinct suppressive T cell fate in a novel form of immunotherapy

  • Kim, Hyun-Joo;Cha, Gil Sun;Joo, Ji-Young;Lee, Juyoun;Kim, Sung-Jo;Lee, Jeongae;Park, So Youn;Choi, Jeomil
    • Journal of Periodontal and Implant Science
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    • v.47 no.5
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    • pp.292-311
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    • 2017
  • Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

The Neuroanatomy and Psychophysiology of Attention (집중의 신경해부와 정신생리)

  • Lee, Sung-Hoon;Park, Yun-Jo
    • Sleep Medicine and Psychophysiology
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    • v.5 no.2
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    • pp.119-133
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    • 1998
  • Attentional processes facilitate cognitive and behavioral performance in several ways. Attention serves to reduce the amount of information to receive. Attention enables humans to direct themselves to appropriate aspects of external environmental events and internal operations. Attention facilitates the selection of salient information and the allocation of cognitive processing appropriate to that information. Attention is not a unitary process that can be localized to a single neuroanatomical region. Before the cortical registration of sensory information, activation of important subcortical structures occurs, which is called as an orienting response. Once sensory information reaches the sensory cortex, a large number of perceptual processes occur, which provide various levels of perceptual resolution of the critical features of the stimuli. After this preattentional processing, information is integrated within higher cortical(heteromodal) systems in inferior parietal and temporal lobes. At this stage, the processing characteristics can be modified, and the biases of the system have a direct impact on attentional selection. Information flow has been traced through sensory analysis to a processing stage that enables the new information to be focused and modified in relation to preexisting biases. The limbic and paralimbic system play significant roles in modulating attentional response. It is labeled with affective salience and is integrated according to ongoing pressures from the motivational drive system of the hypothalamus. The salience of information greatly influences the allocation of attention. The frontal lobe operate response selection system with a reciprocal interaction with both the attention system of the parietal lobe and the limbic system. In this attentional process, the search with the spatial field is organized and a sequence of attentional responses is generated. Affective, motivational and appectitive impulses from limbic system and hypothalamus trigger response intention, preparation, planning, initiation and control of frontal lobe on this process. The reticular system, which produces ascending activation, catalyzes the overall system and increases attentional capacity. Also additional energetic pressures are created by the hypothalamus. As psychophysiological measurement, skin conductance, pupil diameter, muscle tension, heart rate, alpha wave of EEG can be used. Event related potentials also provide physiological evidence of attention during information process. NI component appears to be an electrophysiological index of selective attention. P3 response is developed during the attention related to stimulus discrimination, evaluation and response.

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Ideology and Policy Positions of the Elect in the 21st Korean National Assembly Election (제21대 국회의원 이념성향과 정책 태도)

  • Kang, Woo Chang;Koo, Bon Sang;Lee, Jae Mook;Jung, Jinwung
    • Korean Journal of Legislative Studies
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    • v.26 no.3
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    • pp.37-83
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    • 2020
  • This paper presents the results of 'The Survey on the 21st National Assembly members' conducted by the Korean Association of Party Studies (KAPS) and the Hankyoreh following the 21st Korean National Assembly Election. Since the 16th Korean National Assembly Election, the KAPS has surveyed the candidates and/or the elected regarding their views on major policy issues and perceived self-ideology, which has contributed to our understanding of overtime changes in ideology of political parties in South Korea and their members. This year's survey includes 21 questions on the four major policy issue areas including foreign policy, economy, social issues and cultural issues as well as their perceived ideology. Among the 300 elected, 197 participated in the survey. The results suggest that the Justice Party is most liberal, the United Future Party is most conservative, and the Democratic Party is in the middle on average in terms of issue preference and perceived ideology. Compared to the preceding National Assembly, the partisan gap continues to appear salient in foreign policy, economy, and the cultural issues. In contrast, the gap narrows down in the social issues because the members of the Democratic Party embrace more conservative preference. It is noteworthy to examine whether this shift leads to cooperative decision making on social policies between liberal and conservative parties in the upcoming National Assembly. The composite policy preference index of individual assembly members, on the other hand, shows significant difference among members of different parties. Political parties in South Korea has evolved from a group of people from the same region into a group of people with distinctive policy preferences.