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Watson A 《Science (New York, N.Y.)》2002,295(5563):2194-2195
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Weng AP Ferrando AA Lee W Morris JP Silverman LB Sanchez-Irizarry C Blacklow SC Look AT Aster JC 《Science (New York, N.Y.)》2004,306(5694):269-271
Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling. 相似文献
215.
Hasegawa K Martin F Huang G Tumas D Diehl L Chan AC 《Science (New York, N.Y.)》2004,303(5658):685-689
Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain-enriched tyrosine phosphatase (PEP) in regulating T cell antigen-receptor function during thymocyte development and peripheral T cell differentiation. Although normal na?ve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function. 相似文献
216.
Mishchenko MI Geogdzhayev IV Rossow WB Cairns B Carlson BE Lacis AA Liu L Travis LD 《Science (New York, N.Y.)》2007,315(5818):1543
Analysis of the long-term Global Aerosol Climatology Project data set reveals a likely decrease of the global optical thickness of tropospheric aerosols by as much as 0.03 during the period from 1991 to 2005. This recent trend mirrors the concurrent global increase in solar radiation fluxes at Earth's surface and may have contributed to recent changes in surface climate. 相似文献
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Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5 总被引:1,自引:0,他引:1
Lederman MM Veazey RS Offord R Mosier DE Dufour J Mefford M Piatak M Lifson JD Salkowitz JR Rodriguez B Blauvelt A Hartley O 《Science (New York, N.Y.)》2004,306(5695):485-487
Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus-modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention. 相似文献
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