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IFN-gamma is a potent inducer of MHC class I and class II gene expression in cells derived from all lymphoid organs. In the present study we describe the effects of two inhibitors of the ERK signalling pathway on IFN-gamma-induced MHC class I and class II gene expression. U0126 [5,5′-dimethyl-2-urea-3-carboxylic acid (2R)-2-methylpropyl ester], a highly selective inhibitor of MEK1 and MEK2, and PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one], a MEK inhibitor that blocks only one of the three MEK isoforms, completely blocked MHC class I gene expression in IFN-gamma-treated U937 cells and partially inhibited the IFN-gamma-induced expression of MHC class II genes, but did not inhibit MHC class I gene expression in IFN-gamma-treated HeLa cells. A MEK inhibitor that blocks all three MEK isoforms, PD325901, also blocked IFN-gamma-induced MHC class I and class II expression in U937 cells. PD325901 was approximately 1000-fold more potent in inhibiting MHC class I expression. In contrast, the MEK2 inhibitor, PD184161 (4-anilino-6-(4-chlorophenyl)-1,3-dihydro-2
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Wingneo® INFINITY 2021 § (Windows10対応)âƒâ¬ãƒãƒˆ(Windows10対応) ï¾€KIN11モãƒãƒˆ KIN11Wading into the gory details of the Zombrero murder trial may be distasteful to anyone with a sense of justice, but it’s a particularly nasty tale.
Witnesses recounted in detail how William “Crazy” Willie Zombrero and his accomplices, who have been acquitted of the murder, pumped a drug into a Queens jogger in 1997. The seven-year-old victim, Troy Sears, is paralyzed from the waist down and has soldiered on for more than a decade after the attack.
The harrowing case, which could drag on for years, also brings to the courtroom a vivid portrait of life in the notorious South Bronx and the persistence of a vicious gangland culture.
Zombrero, his crew and the four other gang members — including the defendant Michael Dowtin, who is serving a life sentence for the crime — were accused of attacking Sears and then stealing the $2,500 the assault left him with.
After Dowtin’s conviction, he was offered a deal by prosecutors that would have given him a 25-year prison sentence in exchange for identifying the “weak link” in the gang, according to a source close to the investigation. Dowtin met with an undercover cop and was recorded discussing the possibility of testifying against his cohorts.
But Dowtin and the alleged ringleader, fellow defendant Joseph Bunch, didn’t accept the deal. They were convicted at a second trial and sentenced to 15 and 17 years in prison respectively.
Because of the deal, prosecutors declined to request a third trial.
“I think that if Dowtin had chosen to testify in the first trial, it would have sent a message that the gang would be punished,” said defense lawyer Mark Kyriakis. “That was the goal.”
Zombrero wasn’t charged with any connection to the Sears case, which remained unsolved for years.
“The NYPD saw and exposed this
