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...
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,...
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...
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...
Fluorinated alkyl substances, which can be persistent, toxic, and
bioaccumulative, have been quantitated in many densely populated and
remote regions, including in air, surface waters, groundwater, and biota;
however, little is known about their transport or behavior in the environment.
Wastewater effluent is one of the principal routes for introducing...
Prior to cell cleavage, cytokinetic proteins are recruited into the nascent actomyosin contractile ring. Interactions between spindle microtubules and the cell cortex play a critical role in this recruitment. However, direct evidence for physical interaction between microtubules and the cortex has been lacking. Here we reveal the physical connection between...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. Defining toxicity mechanisms for this large family of multi-ring structures and substituted derivatives is a substantial challenge. Several PAHs, such as benzo(a)pyrene (BaP), are mutagenic, toxic to wildlife, and classified as probable...
Studies using the pluripotent embryonic carcinoma cell line, P19, as a retinoic acid (RA)-responsive model system have been instrumental towards our understanding of the RA-dependent signaling pathways in development and homeostasis. Grp1-associated scaffold protein (GRASP; also known as Tamalin) was first identified by our group, as a gene robustly induced...
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Mark Leid
Studies using the pluripotent embryonic carcinoma cell line, P19, as a
The atmospheric transport and deposition of semi-volatile organic compounds (SOCs), including current and historic use pesticides, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), to mountain ecosystems may result in the exposure of tadpoles to these SOCs. This exposure has been implicated in amphibian population declines in California. Tadpoles encounter...