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      • Increased Cytokine Production in Interleukin-18 Receptor α-deficient Cells Is Associated with Dysregulation of Suppressors of Cytokine Signaling

        Nold-Petry, Claudia A.,Nold, Marcel F.,Nielsen, Jason W.,Bustamante, Alex,Zepp, Jarod A.,Storm, Kathleen A.,Hong, Jae-Woo,Kim, Soo-Hyun,Dinarello, Charles A. American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.38

        <P>Since interleukin (IL)-18 is a proinflammatory cytokine, mice lacking IL-18 or its ligand-binding receptor (IL-18R) should exhibit decreased cytokine and chemokine production. Indeed, production of IL-1alpha, IL-6, and MIP-1alpha was reduced in IL-18 knock-out (ko) mouse embryonic fibroblast (MEF)-like cells. Unexpectedly, we observed a paradoxical 10-fold increase in IL-1beta-induced IL-6 production in MEF cells from mice deficient in the IL-18R alpha-chain (IL-18Ralpha) compared with wild type MEF. Similar increases were observed for IL-1alpha, MIP-1alpha, and prostaglandin E2. Likewise, coincubation with a specific IL-18Ralpha-blocking antibody augmented IL-1beta-induced cytokines in wild type and IL-18 ko MEF. Stable lines of IL-18Ralpha-depleted human A549 cells were generated using shRNA, resulting in an increase of IL-1beta-induced IL-1alpha, IL-6, and IL-8 compared to scrambled small hairpin RNA. In addition, we silenced IL-18Ralpha with small interfering RNA in primary human blood cells and observed up to 4-fold increases in the secretion of lipopolysaccharide- and IL-12/IL-18-induced IL-1beta, IL-6, interferon-gamma, and CD40L. Mechanistically, despite increases in Stat1 and IL-6, induction of SOCS1 and -3 (suppressor of cytokine signaling 1 and 3) was markedly reduced in the absence of IL-18Ralpha. Consistent with these observations, activation of the p38alpha/beta and ERK1/2 MAPKs and of protein kinase B/Akt increased in IL-18Ralpha ko MEF, whereas the negative feedback kinase MSK2 was more active in IL-18 ko cells. These data reveal a role for SOCS1 and -3 in the seemingly paradoxical hyperresponsive state in cells deficient in IL-18Ralpha, supporting the concept that IL-18Ralpha participates in both pro- and anti-inflammatory responses and that an endogenous ligand engages IL-18Ralpha to deliver an inhibitory signal.</P>

      • IL-32-dependent effects of IL-1 on endothelial cell functions

        Nold-Petry, C. A.,Nold, M. F.,Zepp, J. A.,Kim, S.-H.,Voelkel, N. F.,Dinarello, C. A. Proceedings of the National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.10

        <P>Increasing evidence demonstrates that interleukin (IL)-32 is a pro-inflammatory cytokine, inducing IL-1alpha, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and chemokines via nuclear factor (NF)-kappaB, p38 mitogen-activated protein kinase (MAPK), and activating protein (AP)-1 activation. Here we report that IL-32 is expressed and is also functional in human vascular endothelial cells (EC) of various origins. Compared with primary blood monocytes, high levels of IL-32 are constitutively produced in human umbilical vein EC (HUVEC), aortic macrovascular EC, and cardiac as well as pulmonary microvascular EC. At concentrations as low as 0.1 ng/ml, IL-1beta stimulated IL-32 up to 15-fold over constitutive levels, whereas 10 ng/ml of TNFalpha or 100 ng/ml of lipopolysaccharide (LPS) were required to induce similar quantities of IL-32. IL-1beta-induced IL-32 was reduced by inhibition of the IkappaB kinase-beta/NF-kappaB and ERK pathways. In addition to IL-1beta, pro-coagulant concentrations of thrombin or fresh platelets increased IL-32 protein up to 6-fold. IL-1beta and thrombin induced an isoform-switch in steady-state mRNA levels from IL-32alpha/gamma to beta/epsilon. Adult EC responded in a similar fashion. To prove functionality, we silenced endogenous IL-32 with siRNA, decreasing intracellular IL-32 protein levels by 86%. The knockdown of IL-32 resulted in reduction of constitutive as well as IL-1beta-induced intercellular adhesion molecule-1 (ICAM-1) (of 55% and 54%, respectively), IL-1alpha (of 62% and 43%), IL-6 (of 53% and 43%), and IL-8 (of 46% and 42%). In contrast, the anti-inflammatory/anti-coagulant CD141/thrombomodulin increased markedly when IL-32 was silenced. This study introduces IL-32 as a critical regulator of endothelial function, expanding the properties of this cytokine relevant to coagulation, endothelial inflammation, and atherosclerosis.</P>

      • KCI등재
      • Endogenous IL-32 controls cytokine and HIV-1 production.

        Nold, Marcel F,Nold-Petry, Claudia A,Pott, Gregory B,Zepp, Jarod A,Saavedra, Milene T,Kim, Soo-Hyun,Dinarello, Charles A Williams Wilkins 2008 JOURNAL OF IMMUNOLOGY Vol.181 No.1

        <P>IL-32, a proinflammatory cytokine that activates the p38MAPK and NF-kappaB pathways, induces other cytokines, for example, IL-1beta, IL-6, and TNF-alpha. This study investigated the role of endogenous IL-32 in HIV-1 infection by reducing IL-32 with small interfering (si)RNA in freshly infected PBMC and in the latently infected U1 macrophage cell line. When PBMC were pretreated with siRNA to IL-32 (siIL-32), IL-6, IFN-gamma, and TNF-alpha were reduced by 57, 51, and 36%, respectively, compared with scrambled siRNA. Cotransfection of NF-kappaB and AP-1 reporter constructs with siIL-32 decreased DNA binding of these transcription factors by 42 and 46%, respectively. Cytokine protein array analysis revealed that the inhibitory activity of siIL-32 primarily targeted Th1 and proinflammatory cytokines and chemokines, e.g., MIP-1alpha/beta. Unexpectedly, HIV-1 production (as measured by p24) increased 4-fold in these same PBMC when endogenous IL-32 was reduced. Because IFN-gamma was lower in siIL-32-treated PBMC, we blocked IFN-gamma bioactivity, which enhanced the augmentation of p24 by siIL-32. Furthermore, siIL-32 reduced the natural ligands of the HIV-1 coreceptors CCR5 (MIP-1alpha/beta and RANTES) and CXCR4 (SDF-1). Inhibition of endogenous IL-32 in U1 macrophages also increased HIV-1. When rhIL-32gamma was added to these cells, p24 levels fell by 72%; however, in the same cultures IFN-alpha increased 4-fold. Blockade of IFN-alpha/beta bioactivity in IL-32gamma-stimulated U1 cells revealed that IFN-alpha conveys the anti-HIV-1 effect of rhIL-32gamma. In summary, depletion of endogenous IL-32 reduced the levels of Th1 and proinflammatory cytokines but paradoxically increased p24, proposing IL-32 as a natural inhibitor of HIV-1.</P>

      • KCI등재

        연구논문 : 유럽연합의 스포츠 교육 및 훈련 분야에 대한 고찰

        김홍남 ( Hong Nam Kim ),카렌페트리 ( Karen Petry ) 아시아문화학술원 2015 인문사회 21 Vol.6 No.3

        니스와 리스본 조약의 채택 이후, 스포츠는 유럽연합의 활동에서 우위를 차지해 왔다. 이는 공식적인 의사소통과 준비 활동에 반영되어 있다. 이 새로운 정책의 포커스는 전반적인 스포츠 분야의 교육과 훈련의 역할에 있었고, 안티도핑, 통합, 자원봉사의 역할과 이중 커리어에 특수한 포커스를 두었다. 스포츠분야의 최근 발달은 교육과 고용 등 유럽연합 정책의 구조 틀 안에서 조정되고 이루어지며, 노동의 자유로운 이동에 대한 명령, 볼로냐 프로세스, 평생학습과 유럽 인증 프레임워크와 연결된다. 이 논문은 후기 리스본 조약 시기에 핵심 사안을 탐구하며 지금까지 스포츠 교육과 훈련에 미치는 맥락을 고려하였다. 논문은 1990년대 초기 이후 스포츠 과학, 교육, 취업과 관련된 전문적네트워크 안에서 발생하는 단편화과정과 새로운 유럽연합 정책의 맥락에서 잠재적인 함축의 미를 강조한다. Since the Nice and Lisbon Treaties were concluded, sports have gained advantages in activities of the EU. This is reflected in official communication and preparatory activities. The special focus of this new policy was given to education and training in the sporting sector, anti-doping, integration, the roles of volunteers and double careers. Recent developments in sports has been adjusted and achieved in the framework of EU policy also including education and employment, and is related with the rules that cover the free movement of labor, the Bologna process, continuing education and the EU authorized framework. This study investigated central issues at the time when the late Treaty of Lisbon was concluded and considered the context that influences sports education and training. This study focused on potential positive aspects of the implications within the process of fragmentation which occurs in professional networks that cover sports science, education and employment and the context of the new EU policy.

      • KCI등재

        Effects of Chemical Stabilizers on an Expansive Clay

        Honghua Zhao,Louis Ge,Thomas M. Petry,Yi-Zhen Sun 대한토목학회 2014 KSCE JOURNAL OF CIVIL ENGINEERING Vol.18 No.4

        Expansive clays exhibit a high potential for the volume change behavior when the soil moisture changes. The estimated annualcost of the damage to the facilities built on expansive clay in the United States exceeds 9 billion dollars. Because of the physicochemicalnature of the expansive clay, the use of chemical agents to improve their engineering properties is common. This researchinvestigated the effects of chemical agents on an expansive soil from Texas through a laboratory injection method. The agents used inthis study included lime, potassium based agents, and a group of ionic agents. Swelling tests, chemical tests, and soil suction testswere used to evaluate the stabilizing effects of those chemical agents. The testing results indicated that potassium based stabilizer, isan effective stabilizing agent to control the swelling potential of the expansive clay. It can also be injected in the field to build amoisture barrier. The chemical tests on the injected Texas clay showed that the stabilizing mechanism of the ionic agents is possiblythrough the cations’ exchange and the increase of the cations’ concentrations in the soil pore water.

      • KCI등재

        Effect of Heifer Frame Score on Growth, Fertility, and Economics

        S. Senturklu,D.G. Landblom,G.A. Perry,T. Petry 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.1

        A non-traditional forage-based protocol was employed to evaluate replacement heifer growth, fertility, and economics between small frame (SF, 3.50; n = 50) and large frame (LF, 5.56; n = 50) heifers using three increasing gain growth phases. Preceding an 85 d growing-breeding period (Phase 3; P3) the heifers were managed as a common group for Phases 1 and 2 (P1 and P2). During P1, heifers grazed common fields of unharvested corn and corn residue (total digestible nutrients [TDN] 56%) with supplemental hay. For P2, heifers grazed early spring crested wheatgrass pasture (CWG; TDN 62%) that was followed by the final P3 drylot growing and breeding period (TDN 68%). Small frame heifers were lighter at the end of P1 in May and at the start of P3 breeding in August (p = 0.0002). Percent of mature body weight (BW) at the end of P1 (209 d) was 48.7% and 46.8%, respectively, for the SF and LF heifers and the percent pubertal was lower for SF than for LF heifers (18.0% vs 40.0%; p = 0.02). At breeding initiation (P3), the percentage of mature BW was 57.8 and 57.2 and the percentage pubertal was 90.0 and 96.0 (p = 0.07) for the SF and LF heifers, respectively; a 5-fold increase for SF heifers. Breeding cycle pregnancy on days 21, 42, and 63, and total percent pregnant did not differ (p>0.10). In drylot, SF heifer dry matter intake (DMI) was 20.1% less (p = 0.001) and feed cost/d was 20.3% lower (p = 0.001), but feed cost/kg of gain did not differ between SF and LF heifers (p = 0.41). Economically important live animal measurements for muscling were measured in May and at the end of the study in October. SF heifers had greater L. dorsi muscle area per unit of BW than LF heifers (p = 0.03). Small frame heifer value was lower at weaning (p = 0.005) and the non-pregnant ending heifer value was lower for SF heifers than for the LF heifers (p = 0.005). However, the total development cost was lower for SF heifers (p = 0.001) and the net cost per pregnant heifer, after accounting for the sale of non-pregnant heifers, was lower for SF heifers (p = 0.004). These data suggest that high breeding efficiency can be attained among March-April born SF and LF virgin heifers when transitioned to a more favorable May-June calving period through the strategic use of grazed and harvested forages resulting in a lower net cost per pregnant SF heifer.

      • SCIESCOPUSKCI등재
      • SCIESCOPUSKCI등재

        Effect of Heifer Frame Score on Growth, Fertility, and Economics

        Senturklu, S.,Landblom, D.G.,Perry, G.A.,Petry, T. Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.1

        A non-traditional forage-based protocol was employed to evaluate replacement heifer growth, fertility, and economics between small frame (SF, 3.50; n = 50) and large frame (LF, 5.56; n = 50) heifers using three increasing gain growth phases. Preceding an 85 d growing-breeding period (Phase 3; P3) the heifers were managed as a common group for Phases 1 and 2 (P1 and P2). During P1, heifers grazed common fields of unharvested corn and corn residue (total digestible nutrients [TDN] 56%) with supplemental hay. For P2, heifers grazed early spring crested wheatgrass pasture (CWG; TDN 62%) that was followed by the final P3 drylot growing and breeding period (TDN 68%). Small frame heifers were lighter at the end of P1 in May and at the start of P3 breeding in August (p = 0.0002). Percent of mature body weight (BW) at the end of P1 (209 d) was 48.7% and 46.8%, respectively, for the SF and LF heifers and the percent pubertal was lower for SF than for LF heifers (18.0% vs 40.0%; p = 0.02). At breeding initiation (P3), the percentage of mature BW was 57.8 and 57.2 and the percentage pubertal was 90.0 and 96.0 (p = 0.07) for the SF and LF heifers, respectively; a 5-fold increase for SF heifers. Breeding cycle pregnancy on days 21, 42, and 63, and total percent pregnant did not differ (p>0.10). In drylot, SF heifer dry matter intake (DMI) was 20.1% less (p = 0.001) and feed cost/d was 20.3% lower (p = 0.001), but feed cost/kg of gain did not differ between SF and LF heifers (p = 0.41). Economically important live animal measurements for muscling were measured in May and at the end of the study in October. SF heifers had greater L. dorsi muscle area per unit of BW than LF heifers (p = 0.03). Small frame heifer value was lower at weaning (p = 0.005) and the non-pregnant ending heifer value was lower for SF heifers than for the LF heifers (p = 0.005). However, the total development cost was lower for SF heifers (p = 0.001) and the net cost per pregnant heifer, after accounting for the sale of non-pregnant heifers, was lower for SF heifers (p = 0.004). These data suggest that high breeding efficiency can be attained among March-April born SF and LF virgin heifers when transitioned to a more favorable May-June calving period through the strategic use of grazed and harvested forages resulting in a lower net cost per pregnant SF heifer.

      • KCI등재

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