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- 저자 : Oestreich, Kenneth (검색결과 2 건)
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Youngblood, Ben,Oestreich, Kenneth ,J.,Ha, Sang-Jun,Duraiswamy, Jaikumar,Akondy, Rama ,S.,West, Erin ,E.,Wei, Zhengyu,Lu, Peiyuan,Austin, James ,W.,Riley, James ,L.,Boss, Jeremy&nb Elsevier 2011 Immunity Vol.35 No.3
<P><B>Summary</B></P><P>Functionally exhausted T cells have high expression of the PD-1 inhibitory receptor, and therapies that block PD-1 signaling show promise for resolving chronic viral infections and cancer. By using human and murine systems of acute and chronic viral infections, we analyzed epigenetic regulation of PD-1 expression during CD8<SUP>+</SUP> T cell differentiation. During acute infection, naive to effector CD8<SUP>+</SUP> T cell differentiation was accompanied by a transient loss of DNA methylation of the <I>Pdcd1</I> locus that was directly coupled to the duration and strength of T cell receptor signaling. Further differentiation into functional memory cells coincided with <I>Pdcd1</I> remethylation, providing an adapted program for regulation of PD-1 expression. In contrast, the <I>Pdcd1</I> regulatory region was completely demethylated in exhausted CD8<SUP>+</SUP> T cells and remained unmethylated even when virus titers decreased. This lack of DNA remethylation leaves the <I>Pdcd1</I> locus poised for rapid expression, potentially providing a signal for premature termination of antiviral functions.</P> <P><B>Highlights</B></P><P>► <I>Pdcd1</I> locus demethylation is coupled to naive to effector CD8<SUP>+</SUP> T cell differentiation ► After <I>Pdcd1</I> remethylation, select CpGs remain unmethylated in memory CD8<SUP>+</SUP> T cells ► Exhausted virus-specific CD8<SUP>+</SUP> T cells retain an unmethylated <I>Pdcd1</I> regulatory region ► Human CD8<SUP>+</SUP> T cells specific to chronic viruses retain an unmethylated <I>PDCD1</I> locus</P>
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Omann, Lukas,Pudasaini, Bimal,Irran, Elisabeth,Klare, Hendrik F. T.,Baik, Mu-Hyun,Oestreich, Martin Royal Society of Chemistry 2018 Chemical science Vol.9 No.25
<▼1><P>Substituent exchange reactions of silylium ions can be steered in opposite directions. The judicious choice of the hydrosilane and the counteranion enables the selective formation of either triaryl- or trialkylsilylium ions.</P></▼1><▼2><P>An in-depth experimental and theoretical study of the substituent exchange reaction of silylium ions is presented. Apart from the substitution pattern at the silicon atom, the selectivity of this process is predominantly influenced by the counteranion, which is introduced with the trityl salt in the silylium ion generation. In contrast to Müller's protocol for the synthesis of triarylsilylium ions under kinetic control, the use of Reed's carborane anions leads to contact ion pairs, allowing selective formation of trialkylsilylium ions under thermodynamic control. DFT calculations finally revealed an unexpected mechanism for the rate-determining alkyl exchange step, which is initiated by an unusual 1,2-silyl migration in the intermediate <I>ipso</I>-disilylated arenium ion. The resulting <I>ortho</I>-disilylated arenium ion can then undergo an alkyl transfer <I>via</I> a low-barrier five-centered transition state.</P></▼2>
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