• Title/Summary/Keyword: Dendritic

Search Result 768, Processing Time 0.023 seconds

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
    • /
    • v.47 no.5
    • /
    • pp.292-311
    • /
    • 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.

Analysis of runoff speed depending on the structure of stormwater pipe networks (우수관망 구조에 따른 유출 속도 분석)

  • Lee, Jinwoo;Chung, Gunhui
    • Journal of Korea Water Resources Association
    • /
    • v.51 no.2
    • /
    • pp.121-129
    • /
    • 2018
  • Rainfall falling in the impervious area of the cities flows over the surface and into the stormwater pipe networks to be discharged from the catchment. Therefore, it is very important to determine the size of stormwater pipes based on the peak discharge to mitigate urban flood. Climate change causes the severe rainfall in the small area, then the peak rainfall can not be discharged due to the capacity of the stormwater pipes and causes the urban flood for the short time periods. To mitigate these type of flood, the large stormwater pipes have to be constructed. However, the economic factor is also very important to design the stormwater pipe networks. In this study, 4 urban catchments were selected from the frequently flooded cities. Rainfall data from Seoul and Busan weather stations were applied to calculate runoff from the catchments using SWMM model. The characteristics of the peak runoff were analyzed using linear regression model and the 95% confidence interval and the coefficient of variation was calculated. The drainage density was calculated and the runoff characteristics were analyzed. As a result, the drainage density were depended on the structure of stormwater pipe network whether the structures are dendritic or looped. As the drainage density become higher, the runoff could be predicted more accurately. it is because the possibility of flooding caused by the capacity of stormwater pipes is decreased when the drainage density is high. It would be very efficient if the structure of stormwater pipe network is considered when the network is designed.

Characterization of Synthesized Strontianite: Effects of Ionic Strength, Temperature, and Aging Time on Crystal Morphology and Size (온도, 이온세기 및 결정성장시간에 따른 합성 스트론티아나이트(SrCO3) 특성 연구)

  • Lee, Seon Yong;Lee, Choong Hyun;Hur, Hyuck;Seo, Jieun;Lee, Young Jae
    • Journal of the Mineralogical Society of Korea
    • /
    • v.28 no.2
    • /
    • pp.195-207
    • /
    • 2015
  • Physical properties of strontianite ($SrCO_3$) synthesized under variable conditions such as different ionic strength, temperature, and aging time were investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). All synthesized samples show a single phase of strontianite. Crystallinity of the synthesized strontianite increases with increasing temperature and ionic strength with $NaNO_3$. Crystal sizes of the samples increase dramatically, and their morphology changes from rod or dendritic to prismatic shape as ionic strength and temperature of the solution increase. In addition, crystal sizes increase, and their morphology changes from rod or prismatic crystals to spheroidal aggregates with increasing aging time. These results suggest that changes in conditions of the synthesis for strontianite play an important role in controlling the crystallinity and morphology of results provide crucial information on the prediction for the physical properties of strontianite under different conditions during the formation of strontianite crystals.

Terminals of Antennal Receptor Cells in the Antennal Lobe of the Bunenv. Pieris rapae L.(Insects, Lepidoptera) (배추흰나비 뇌의 촉각엽에 뻗은 촉각지각신경세포의 축색종말)

  • 이봉희;김우갑
    • The Korean Journal of Zoology
    • /
    • v.31 no.4
    • /
    • pp.334-343
    • /
    • 1988
  • Five types of synaPses were differentiated in the antennal lobe or Pieris rapoe. aev are in general axo-dendritic synapses and have symmetrical contacts. The type I synapses contain the uniformly round vesicles of medium size, and consist of the 11% of all synapses in the antennal lobe. The type synapses are filled with the small flat and densely arranged (19%). The type III synapses possess medium-sized round vesicles and dense core ones(24%). The type IV synapses are characterized by such three kinds of vesicles as small round, small flat and dense core vesicles(33%). The type V synapses exhibit the presence of medium-sized round, large round and dense core vesicles(13%). The removal of the left antenna on its proximal portion caused the type IV boutons of the above ave types in ipsilateral antennal lobe to turn into dark or semidark degenerative changes. Therefore, it was concluded that many of the antennal receptor cells projected into the brain terminate in the antennal lobe to form type IV synapses together with the dendrites. 배추회나비 뇌의 촉각엽에 있는 신경세포들은 5가지의 신경연접을 형성하는 것으로 관찰되었다. 이 신경연접들은 모두 축색과 수상돌기간의 연접으로 대칭연접이었다. 제1형 신경연접은 축색종말내에 중등도크기의 단형 연접소포를 가지고 있었고, 촉각엽에 있는 5가지의 신경연접중 11%의 출현빈도수로 관찰되었다. 제2형 신경연접의 축색종말에는 장형과 도형의 2가지 연접소포가 포함되어 있었는데, 모두 소형이었으며 이같은 연접소포들이 축색 종말내에서 조밀하게 관찰되었다. 제2형 신경연접의 출현 빈도수는 19%이었다. 제3형 신경연접은 축색 종말내에 중등도크기의 도형 연접소포와 DENSE CORE VESICLE을 포함하고 있었고 그 출현빈도수는 24%이었다. 제4형 신경연접은 축색총말내에 소형의 도형, 소형의 장형 연접소포 및 DENSE CORE VESICLE의 3가지 연접소포를 가지고 있었고 출현빈도수는 촉각엽에서 가장 큰 33%이었다. 제5형 신경연접은 축색종말내에 중등도크기의 원형, 대형의 원형연접소포 및 DENSE CORE VESICLE을 포함하였고 13%의 출현빈도수로 관찰되었다. 배추횐나비의 촉각에 있는 지각신경세포가 뇌의 촉각엽으로 뻗어 들어가 위의 5가지 신경연접중 어느 형을 형성하는지를 관찰하기 위하여 좌측 촉각의 기부를 제거하여 지각신경세포를 절단하였는데 그 결과, 좌측 촉각엽에서 제4형의 신경연접이 퇴행성 변화를 나타내었다. 그러므로 촉각의 지각신경세포는 뇌의 같은 족 촉각엽에 뻗어와 제4형 신경연접을 형성한다고 결론되었다.

  • PDF

RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction

  • Jung, In-Duk;Kim, Hye-Young;Park, Jin-Wook;Lee, Chang-Min;Noh, Kyung-Tae;Kang, Hyun-Kyu;Heo, Deok-Rim;Lee, Su-Jung;Son, Kwang-Hee;Park, Hee-Ju;Shin, Sung-Jae;Park, Jong-Hwan;Ryu, Seung-Wook;Park, Yeong-Min
    • BMB Reports
    • /
    • v.45 no.2
    • /
    • pp.79-84
    • /
    • 2012
  • In asthma, T helper 2 (TH2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated $CD^{4+}$ T cells. Dendritic cells played an important role in determining the fate of naive T cells into either $T_H1$ or $T_H2$ cells. We determined whether RG-II regulates the $T_H1/T_H2$ immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon-gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.

Beyond Clot Dissolution; Role of Tissue Plasminogen Activator in Central Nervous System

  • Kim, Ji-Woon;Lee, Soon-Young;Joo, So-Hyun;Song, Mi-Ryoung;Shin, Chan-Young
    • Biomolecules & Therapeutics
    • /
    • v.15 no.1
    • /
    • pp.16-26
    • /
    • 2007
  • Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

Inhibition Effect of Taxilli Ramulus Extract on Osteoclast Differentiation and Bone Resorption (상기생 추출물이 파골세포 분화와 골흡수 억제에 미치는 효과)

  • Baek, Jong Min;Kim, Ju Young;Lee, Myeung Su;Jeung, Woo Jin;Moon, Seo Young;Jeon, Byung Hoon;Oh, Jae Min;Choi, Min Kyu
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.27 no.4
    • /
    • pp.431-436
    • /
    • 2013
  • Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

Study on Color Formation of Cheolhwa Buncheong Stoneware Glaze by Pigment Raw Materials of Iron Oxides and Firing Conditions (철산화물 안료 원료와 번조조건에 따른 철화분청사기의 유약 발색 연구)

  • Kim, Ji Hye;Han, Min Su;Jeong, Young Yu;Choi, Sung Jae
    • Journal of Conservation Science
    • /
    • v.35 no.6
    • /
    • pp.573-587
    • /
    • 2019
  • In this study, reproducing specimens were made from mixing domestically produced magnetite, clay and non-plastic raw materials to reproduce the pigments used in the manufacture of traditional cheolhwa buncheong stoneware. In order to reveal the color fomation of glaze, 30 specimens with good color development were analyzed scientifically. Magnetite, which is the main raw material of the pigment, is a pigment capable of creating a dark black color in a reducing environment at 1,200℃. However, it reacts with the additionally added lime component and discolors to greenish yellow color in oxidizing environment at 1,230℃. Hematite is not significantly affected by the firing temperature and environment, but develops a dark black color when mixed with clay with iron content of more than 10%. The fluidity of the pigment is determined by R2O3/RO2 value, which also affects the color development. In the microtexture observation, the color formation of the glaze layer and the iron oxide crystals identified some differences depending on the particle size of the pigment and the firing environment. Reproduced specimens made of magnetite are present in the form of aggregates of iron oxide in the interface between glaze layer and slip layer in the oxidizing environment at 1,200℃. However, in the reducing environment, aggregates of iron oxides do not exist in the reproduced specimens, and they are homogeneously distributed in the glaze layer and formed a dark black color. In contrast, hematite-based specimens form dendritic structures in the glaze layer in an oxidizing environment and develop black.

High Strength Nanostructured Metastable Alloys

  • Eckert, Jurgen;Bartusch, Birgit;Schurack, Frank;He, Guo;Schultz, Ludwig
    • Journal of Powder Materials
    • /
    • v.9 no.6
    • /
    • pp.394-408
    • /
    • 2002
  • Nanostructured high strength metastable Al-, Mg- and Ti-based alloys containing different amorphous, quasicrystalline and nanocrystalline phases are synthesized by non-equilibrium processing techniques. Such alloys can be prepared by quenching from the melt or by powder metallurgy techniques. This paper focuses on one hand on mechanically alloyed and ball milled powders containing different volume fractions of amorphous or nano-(quasi)crystalline phases, consolidated bulk specimens and, on the other hand. on cast specimens containing different constituent phases with different length-scale. As one example. $Mg_{55}Y_{15}Cu_{30}$- based metallic glass matrix composites are produced by mechanical alloying of elemental powder mixtures containing up to 30 vol.% $Y_2O_3$ particles. The comparison with the particle-free metallic glass reveals that the nanosized second phase oxide particles do not significantly affect the glass-forming ability upon mechanical alloying despite some limited particle dissolution. A supercooled liquid region with an extension of about 50 K can be maintained in the presence of the oxides. The distinct viscosity decrease in the supercooled liquid regime allows to consolidate the powders into bulk samples by uniaxial hot pressing. The $Y_2O_3$ additions increase the mechanical strength of the composites compared to the $Mg_{55}Y_{15}Cu_{30}$ metallic glass. The second example deals with Al-Mn-Ce and Al-Cu-Fe composites with quasicrystalline particles as reinforcements, which are prepared by quenching from the melt and by powder metallurgy. $Al_{98-x}Mn_xCe_2$ (x =5,6,7) melt-spun ribbons containing a major quasicrystalline phase coexisting with an Al-matrix on a nanometer scale are pulverized by ball milling. The powders are consolidated by hot extrusion. Grain growth during consolidation causes the formation of a micrometer-scale microstructure. Mechanical alloying of $Al_{63}Cu_{25}Fe_{12}$ leads to single-phase quasicrystalline powders. which are blended with different volume fractions of pure Al-powder and hot extruded forming $Al_{100-x}$$(Al_{0.63}Cu_{0.25}Fe_{0.12})_x$ (x = 40,50,60,80) micrometer-scale composites. Compression test data reveal a high yield strength of ${\sigma}_y{\geq}$700 MPa and a ductility of ${\varepsilon}_{pl}{\geq}$5% for than the Al-Mn-Ce bulk samples. The strength level of the Al-Cu-Fe alloys is ${\sigma}_y{\leq}$550 MPa significantly lower. By the addition of different amounts of aluminum, the mechanical properties can be tuned to a wide range. Finally, a bulk metallic glass-forming Ti-Cu-Ni-Sn alloy with in situ formed composite microstructure prepared by both centrifugal and injection casting presents more than 6% plastic strain under compressive stress at room temperature. The in situ formed composite contains dendritic hcp Ti solid solution precipitates and a few $Ti_3Sn,\;{\beta}$-(Cu, Sn) grains dispersed in a glassy matrix. The composite micro- structure can avoid the development of the highly localized shear bands typical for the room temperature defor-mation of monolithic glasses. Instead, widely developed shear bands with evident protuberance are observed. resulting in significant yielding and homogeneous plastic deformation over the entire sample.

Effect of Calpain Inhibitors on $Ca^{2+}-Induced$ Suppression of Neurite Outgrowth in Isolated Hippocampal Pyramidal Neurons (해마추상체 신경세포에서 칼슘에 의한 신경섬유 성장억제에 대한 칼파인 억제제의 영향)

  • Song, Dong-Keun;Kater, Stanley B.;Mykles, Donald L.
    • The Korean Journal of Pharmacology
    • /
    • v.29 no.2
    • /
    • pp.165-174
    • /
    • 1993
  • $Ca^{2+}$ is an important regulator of neurite elongation and growth cone movements but the mechanism(s) mediating these $Ca^{2+}-dependent$ effects is unclear. Since cytoskeletal proteins are rapidly degraded by $Ca^{2+}-dependent $ proteinases (calpains) in vitro and in vivo, we investigated whether $Ca^{2+}-induced$ pruning or regression of neuronal processes is mediated by calpains. Isolated hippocampal pyramidal-like neurons were cultured and the ability of the membrane-permeable calpain inhibitors EST (etyl (+)-(2S,3S)-3-[(S)-methyl-1-(3-methlbutylcarbamoyl)-butylcarbamoyl]2-oxiranecarboxylate) and MDL28170 (carbobenzoxyl-Val-Phe-H) to block the $Ca^{2+}$ ionophore A23187-induced suppression in neurite outgrowth was investigated. Addition of 100 nM A23187 to the culture medium resulted in a retraction of dendrites without altering axonal elongation. The addition of 300 nM A23187 to the culture medium resulted in a signiciant decrease in the rate of axonal elongation as well as a retraction of dendritic processes. Administration of EST $(5\;or\;20{\mu}M)$ to the culture medium completely blocked the pruning effect of 100 nM A23187 on dendrites and of 300 nM A23187 on axons, while EST alone did not significantly affect neurite outgrowth rate. MDL 28170 $(20\;{\mu}M)$ showed the same effect as EST in preventing ionophore-induced pruning of dendrites and axons at 100 nM and 300 nM concentrations, respectively, of A23187. EST $(20\;{\mu}M)$ did not block the A23187-induced rise of $[Ca^{2+}]_{i}$ as measured with fura-2. These results show that $Ca^{2+}-induced$ pruning of neurites in isolated hippocampal pyramidal neurons is mediated by calpains.

  • PDF