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    PARP1 and PARylation are increased in chagasic myocardium

    The WT, PARP1+/-, and PARP1-/- mice were genotyped to confirm the presence of two, one and no copies of the PARP1 gene (S1A Fig). We then evaluated the effect of Tc infection on the levels of PARP1 mRNA, protein, and activity in WT and PARP1-/- mice. In PARP1-/- mice, PARP1 mRNA and protein levels remained undetectable before or after Tc infection (Fig 1A–1C). In chronically infected WT (vs. uninfected WT) mice, the myocardial levels of PARP1 mRNA and protein were increased by 220% and 68.8%, respectively (Fig 1A–1C, all, p<0.001). Tissue fractionation/Western blotting showed 130%, 230%, and 141% increase in PARP1 levels in the myocardial cytosolic, nuclear, and mitochondrial fractions of WT.Tc (vs. WT) mice (Fig 1D & 1E, all, p<0.01). Protein PARylation is an indicator of PARP1 activity. Our data showed 43-fold, 44-fold and 30-fold increase in protein PARylation levels, respectively, in the myocardial cytosolic, nuclear, and mitochondrial fractions of WT.Tc (vs. WT) mice (Fig 1F–1K, all, p<0.001). The PARP1-/- mice exhibited a basal PARylation level that was not substantially increased in response to chronic infection (Fig 1F–1K). These results suggest that PARP1 expression and PARylation activity were increased in myocardial fractions (cytosolic, nuclear and mitochondrial) of chagasic WT mice. Other members of the PARP family likely contributed to the slight increase in PARylation level observed in chronically infected PARP1-/- mice.

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    Fifteen children born with a rare muscle-wasting disease would probably not be alive today if not for an experimental treatment that tweaked their genes shortly after they were born.

    The disease, called spinal muscular atrophy, would likely have killed most of them by age two. Amazingly, many of the children can now speak and sit on their own, and a few are even walking—milestones they never would have reached without the treatment. The company behind the drug, AveXis, is seeing the most dramatic results in children who are treated in the first month or two of life.

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    Lampson took the news with a teenager’s instincts: He jumped on the internet to research his disease.

    “I never dwelled on the possibility of death. So I think ultimately that helped me because my immediate response was, ‘What do I do to beat it?’ ” Lampson said. “I never really grasped the gravity of having a cancer diagnosis.”

    Even after learning the cancer had spread through his chest — years later he found out such cases had about a 65 percent five-year survival rate — Lampson still made the trip from his Hilliard, Ohio, home to Iowa for his club soccer team’s regional tournament. The next day, he began an aggressive chemotherapy regimen, which is no longer used, at Nationwide Children’s Hospital in Columbus.

    The drugs attacked the cancer, and the experience sapped Lampson’s youthful innocence.

    “It took an incredibly large toll on me as a person,” said Lampson, who had to put college on hold. “Obviously at 17 years old, everybody graduates high school. Everybody else goes on with their lives. So you find out who really loves you very quickly. … I got incredibly cynical. I started to hate everything.”

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