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- 저자 : Humbles, Alison (검색결과 3 건)
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Lee, Chun Geun,Hartl, Dominik,Lee, Gap Ryol,Koller, Barbara,Matsuura, Hiroshi,Da Silva, Carla A.,Sohn, Myung Hyun,Cohn, Lauren,Homer, Robert J.,Kozhich, Alexander A.,Humbles, Alison,Kearley, Jennifer The Rockefeller University Press 2009 The Journal of experimental medicine Vol.206 No.5
<P>Mouse breast regression protein 39 (BRP-39; Chi3l1) and its human homologue YKL-40 are chitinase-like proteins that lack chitinase activity. Although YKL-40 is expressed in exaggerated quantities and correlates with disease activity in asthma and many other disorders, the biological properties of BRP-39/YKL-40 have only been rudimentarily defined. We describe the generation and characterization of BRP-39<SUP>−/−</SUP> mice, YKL-40 transgenic mice, and mice that lack BRP-39 and produce YKL-40 only in their pulmonary epithelium. Studies of these mice demonstrated that BRP-39<SUP>−/−</SUP> animals have markedly diminished antigen-induced Th2 responses and that epithelial YKL-40 rescues the Th2 responses in these animals. The ability of interleukin13 to induce tissue inflammation and fibrosis was also markedly diminished in the absence of BRP-39. Mechanistic investigations demonstrated that BRP-39 and YKL-40 play an essential role in antigen sensitization and immunoglobulin E induction, stimulate dendritic cell accumulation and activation, and induce alternative macrophage activation. These proteins also inhibit inflammatory cell apoptosis/cell death while inhibiting Fas expression, activating protein kinase B/AKT, and inducing Faim 3. These studies establish novel regulatory roles for BRP-39/YKL-40 in the initiation and effector phases of Th2 inflammation and remodeling and suggest that these proteins are therapeutic targets in Th2- and macrophage-mediated disorders.</P>
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Humble, Travis S.,Cina, Jeffrey A. Korean Chemical Society 2003 Bulletin of the Korean Chemical Society Vol.24 No.8
We present one-color nonlinear wavepacket interferometry (WPI) signal calculations for a system of two electronic levels and one vibrational degree of freedom. We consider two cases, a displaced harmonic oscillator system, which can be treated analytically, and a model photodissociative system, whose WPI signal must be calculated by numerical wavepacket propagation. We show how signals obtained with different combinations of intrapulse-pair phase shifts can be combined to isolate the complex-valued overlap between a given onepulse target wavepacket and a variable three-pulse reference wavepacket. We demonstrate that with a range of inter- and intrapulse-pair delays the complex overlaps and variable reference states can be used to reconstruct the target wavepacket. We compare our results with previous methods for vibronic state reconstruction based on linear WPI and discuss further generalizations of our method.
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Dong, Miao,Seemann, Frauke,Humble, Joseph L.,Liang, Yimin,Peterson, Drew R.,Ye, Rui,Ren, Honglin,Kim, Hui-Su,Lee, Jae-Seong,Au, Doris W.T.,Lam, Yun Wah Elsevier 2017 Fish & shellfish immunology Vol.70 No.-
<P><B>Abstract</B></P> <P>Growing evidence suggests that the immune system of teleost is vulnerable to xenoestrogens, which are ubiquitous in the marine environment. This study detected and identified the major circulatory immune proteins deregulated by 17α-ethinylestradiol (EE2), which may be linked to fish susceptibility to pathogens in the marine medaka, <I>Oryzias melastigma</I>. Fish immune competence was determined using a host resistance assay to pathogenic bacteria <I>Edwardsiella tarda</I>. Females were consistently more susceptible to infection-induced mortality than males. Exposure to EE2 could narrow the sex gap of mortality by increasing infection-induced death in male fish. Proteomic analysis revealed that the major plasma immune proteins of adult fish were highly sexually dimorphic. EE2 induced pronounced sex-specific changes in the plasma proteome, with the male plasma composition clearly becoming “feminised”. Male plasma was found to contain a higher level of fibrinogens, WAP63 and ependymin-2-like protein, which are involved in coagulation, inflammation and regeneration. For the first time, we demonstrated that expression of C1q subunit B (C1Q), an initiating factor of the classical complement pathway, was higher in males and was suppressed in both sexes in response to EE2 and bacterial challenge. Moreover, cleavage and post-translational modification of C3, the central component of the complement system, could be altered by EE2 treatment in males (C3dg down; C3g up). Multiple regression analysis indicated that C1Q is possibly an indicator of fish survival, which warrants further confirmation. The findings support the potential application of plasma immune proteins for prognosis/diagnosis of fish immune competence. Moreover, this study provides the first biochemical basis of the sex-differences in fish immunity and how these differences might be modified by xenoestrogens.</P> <P><B>Highlights</B></P> <P> <UL> <LI> EE2 exposure reduces fish resistance to pathogen infection. </LI> <LI> The plasma immune proteins of adult fish are sexually dimorphic. </LI> <LI> Exogenous EE2 can modify the immune plasma proteome. </LI> <LI> The interplay between plasma C1Q and exogenous EE2 warrants further investigation. </LI> </UL> </P>
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