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A Critical Role of PCSK9 in Mediating IL-17-Producing T Cell Responses in Hyperlipidemia
김영욱,Patrick Kee,Delia Danila,Ba-Bie Teng 대한면역학회 2019 Immune Network Vol.19 No.6
We previously demonstrated that atherogenic Ldlr−/−Apobec1−/− (LDb) double knockout mice lacking both low-density lipoprotein receptor (LDLR) and apolipoprotein B mRNA-editing catalytic polypeptide-1 (Apobec1) had increased serum IL-17 levels, with T cell programming shifted towards Th17 cells. In this study, we assessed the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in T cell programming and atherogenesis. We deleted the Pcsk9 gene from LDb mice to generate Ldlr−/−Apobec1−/−Pcsk9−/− (LTp) triple knockout mice. Atherosclerosis in the aortic sinus and aorta were quantitated. Lymphoid cells were analyzed by flow cytometry, ELISA and real-time PCR. Despite of dyslipidemia, LTp mice developed barely detectable atherosclerotic lesions. The IL-17, was very low in plasma and barely detectable in the aortic sinus in the LTp mice. In the spleen, the number of CD4+CD8− cells and splenocytes were much lower in the LDb mice than LTp mice, whereas, the IL-17-producing cells of γδTCR+ T cells and effector memory CD4+ T cells (CD44hiCD4+) in the spleen were significantly higher in the LDb mice than in the LTp mice. The Rorc mRNA expression levels were elevated in LDb mice compared to LTp mice. When re-stimulated with an anti-CD3 Ab, CD44hiCD4+ T cells from LDb mice secreted more IL-17 than those from LTp mice. T cells from LDb mice (with PCSK9) produce more IL-17 at basal and stimulated conditions when compared with LTp mice (without PCSK9). Despite the dyslipidemic profile and the lack of LDLR, atherogenesis is markedly reduced in LTp mice. These results suggest that PCSK9 is associated with changes in T cell programming that contributes to the development of atherosclerosis.
The Properties of Planck Galactic Cold Clumps in the L1495 Dark Cloud
Tang, Mengyao,Liu, Tie,Qin, Sheng-Li,Kim, Kee-Tae,Wu, Yuefang,Tatematsu, Ken’ichi,Yuan, Jinghua,Wang, Ke,Parsons, Harriet,Koch, Patrick M.,Sanhueza, Patricio,Ward-Thompson, D.,Tó,th, L. Viktor,S American Astronomical Society 2018 The Astrophysical journal Vol.856 No.2
Planck Cold Clumps in the <i>λ</i> Orionis Complex. II. Environmental Effects on Core Formation
Yi, Hee-Weon,Lee, Jeong-Eun,Liu, Tie,Kim, Kee-Tae,Choi, Minho,Eden, David,II, Neal J. Evans,Francesco, James Di,Fuller, Gary,Hirano, N.,Juvela, Mika,Kang, Sung-ju,Kim, Gwanjeong,M. Koch, Patrick,Lee, American Astronomical Society 2018 The Astrophysical journal, Supplement series Vol.236 No.2
<P>Based on the 850 mu m dust continuum data from SCUBA-2 at James Clerk Maxwell Telescope (JCMT), we compare overall properties of Planck Galactic Cold Clumps (PGCCs) in the lambda Orionis cloud to those of PGCCs in the Orion A and B clouds. The Orion A and B clouds are well-known active star-forming regions, while the A Orionis cloud has a different environment as a consequence of the interaction with a prominent OB association and a giant H-II region. PGCCs in the lambda Orionis cloud have higher dust temperatures (T-d = 16.13 +/- 0.15 K) and lower values of dust emissivity spectral index (beta = 1.65 +/- 0.02) than PGCCs in the Orion A (T-d = 13.79 +/- 0.21 K, beta = 2.07 +/- 0.03) and Orion B (T-d = 13.82 +/- 0.19 K, beta =1.96 +/- 0.02) clouds. We find 119 substructures within the 40 detected PGCCs and identify them as cores. Out of a total of 119 cores, 15 cores are discovered in the lambda Orionis cloud, while 74 and 30 cores are found in the Orion A and B clouds, respectively. The cores in the lambda Orionis cloud show much lower mean values of size R = 0.08 pc, column density N(H-2) (9.5 +/- 1.2) x 10(22)cm(-2) , number density n(H-2) - (2.9 +/- 0.4) x 10 5 CM -3 , and mass M-core = 1.0 +/- 0.3 M(circle dot)compared to the cores in the Orion A [R = 0.11 pc, N(H-2) = (2.3 +/- 0.3) x 10(23) cm(-2), n(H-2) = (3.8 +/- 0.5) x 10(5)cm(-3) , and M-core = 2.4 +/- 0.3 M-circle dot] and Orion B [R = 0.16 pc, N(H-2) (3.8 +/- 0.4) x 10(23) cm(-2), n(H-2) = (15.6 +/- 1.8) x 10(5) cm(-3) , and M-core = 2.7 +/- 0.3 M-circle dot] clouds. These core properties in the A Orionis cloud can be attributed to the photodissociation and external heating by the nearby H rr region, which may prevent the PGCCs from forming gravitationally bound structures and eventually disperse them. These results support the idea of negative stellar feedback on core formation.</P>