Coibamide A is a methyl-stabilized cyclic depsipeptide with a lariat side chain that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups program based in Panama. Previous testing of this potent and selective growth-inhibitory agent in the National Cancer Institute (NCI) in vitro 60 human...
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or...
Chemicals must be bioavailable for there to be a potential for exposure and consequent risk to human or environmental health. Passive sampling devices (PSDs) are used to quantify the time-integrated concentration of bioavailable contaminants. We demonstrate that PSDs can be paired with the zebrafish developmental toxicity bioassay to produce site-specific,...
Hallmarks of aging include the accumulation of aberrant proteins and a lower resistance to stresses. Because the endoplasmic reticulum (ER) functions to fold proteins and possesses unique stress sensing pathways, the central hypothesis of this dissertation is that the ER is a target of cellular aging and significantly underlies these...
Mutations to superoxide dismutase were the first proven cause of Lou
Gehrig’s disease (amyotrophic lateral sclerosis; ALS) implicating superoxide in
the selective death of motor neurons that characterizes ALS. Nitric oxide
competes effectively with superoxide dismutase for superoxide to form the
powerful oxidant peroxynitrite. Endogenous formation of peroxynitrite can kill...