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101.
102.
Protein-derived cofactors that are composed of covalently crosslinked amino acid side chains are of increasing importance in protein science. These crosslinked protein-derived cofactors (CPDC) are formed either through direct oxidation by metal/O(2)-derived intermediates or through outer sphere oxidation by highly oxidizing cofactors. CPDCs that are formed by outer sphere oxidation do not require side-chain precursors to be coordinated by a metal center, and therefore are more difficult to identify than those formed by direct oxidation. To better understand the propensity for CPDC formation by outer sphere oxidation, the geometrical preferences of CPDCs were examined. The Dezymer algorithm has been used to identify all putative CPDC-forming mutations in 500 proteins. Geometrically, although chemically unrelated, these CPDCs were found to be similar to disulfide-bonded cysteine pairs. Additionally, the percentage of near-sequence pairs (i and i +1 to i and i + 5) increased as the average C(alpha)-C(alpha) distance between the amino acid pairs increased. This survey also examined the protein databank for proteins with pre-attack conformations for CPDCs, using non-bonded contacts reported by Procheck. A total of 323 unique proteins was identified, with 55 being near-sequence amino acid pairs. The high geometric propensity of near-sequence amino acid pairs for forming CPDCs is significant due to difficulties associated with detection by structural or mass spectrometric methods. 相似文献
103.
As the adage says, variety is the spice of life, and despite our best attempts, cells, even those with the same genome, never seem to behave the same. By combining mathematical and experimental analyses, Colman-Lerner and colleagues propose, in a recent issue of Nature, a method to delicately unravel the sources of this variation. Applying their technique to the pheromone response in budding yeast, they show that much of the observed variation originates from cell cycle effects and is dependent on levels of pathway input. 相似文献
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105.
Ajuebor MN Aspinall AI Zhou F Le T Yang Y Urbanski SJ Sidobre S Kronenberg M Hogaboam CM Swain MG 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(12):8027-8037
Fulminant liver failure (FLF) consists of a cascade of events beginning with a presumed uncontrolled systemic activation of the immune system. The etiology of FLF remains undefined. In this study, we demonstrate that CCR5 deficiency promotes the development of acute FLF in mice following Con A administration by preventing activated hepatic CD1d-restricted NKT cells (but not conventional T cells) from dying from activation-induced apoptosis. The resistance of CCR5-deficient NKT cells from activation-induced apoptosis following Con A administration is not due to a defective Fas-driven death pathway. Moreover, FLF in CCR5-deficient mice also correlated with hepatic CCR5-deficient NKT cells, producing more IL-4, but not IFN-gamma, relative to wild-type NKT cells. Furthermore, FLF in these mice was abolished by IL-4 mAb or NK1.1 mAb treatment. We propose that CCR5 deficiency may predispose individuals to the development of FLF by preventing hepatic NKT cell apoptosis and by regulating NKT cell function, establishing a novel role for CCR5 in the development of this catastrophic liver disease that is independent of leukocyte recruitment. 相似文献
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107.
Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis 总被引:7,自引:0,他引:7
Bonder CS Ajuebor MN Zbytnuik LD Kubes P Swain MG 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(1):45-53
Leukocyte infiltration into the liver is paramount to the development of liver injury in hepatitis. Hepatitis occurring after the administration of Con A in mice is felt to be a T lymphocyte-mediated disease. In this study, we report that neutrophils are the key initiators of lymphocyte recruitment and liver injury caused by Con A. The objectives of this study were to investigate the involvement of neutrophils in Con A-induced hepatitis in vivo via intravital microscopy. After Con A administration, we observed a significant increase in leukocyte rolling flux, a decrease in rolling velocity, and an increase in leukocyte adhesion to the hepatic microvasculature. Fluorescence microscopy identified that within 4 h of Con A administration only a minority of the recruited leukocytes were T lymphocytes. Furthermore, immunohistochemistry showed a significant increase in neutrophils recruited to the liver post-Con A treatment in association with liver cell damage, as reflected by elevated serum alanine aminotransferase levels. Using flow cytometry, we observed that Con A could bind directly to neutrophils, which resulted in a shedding of L-selectin, an increase in beta(2)-integrin expression, and the production of reactive oxidants. Following neutrophil depletion, a significant inhibition of Con A-induced CD4+ T lymphocyte recruitment to the liver resulted and complete reduction in hepatic injury, as assessed by serum alanine aminotransferase levels. In summary, the present data support the concept that neutrophils play an important and previously unrecognized role in governing Con A-induced CD4+ T cell recruitment to the liver and the subsequent development of hepatitis. 相似文献
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109.
建立冰乙酸性大鼠胃溃疡模型,采用ABC法进行免疫组织化学染色,观察并探讨胃溃疡对胃壁中HAP1(huntingtin as-soc iated protein 1,HAP1)表达的影响。结果溃疡组大鼠胃壁中HAP1阳性细胞数目及光密度与正常进食的大鼠相比显著增多。 相似文献
110.
针对白色污染的危害及其严重性,综述了治理白色污染的重要技术,并对社会上使用的纸餐具以及相关可降解产品进行了探讨,最后提出要想彻底解决白色污染问题,就必须政策和技术并重。 相似文献