IMPACT Human
Description
Framework Components
The IMPACT Human model evaluates chemical hazards through four interconnected factors:
Per- and Polyfluoroalkyl Substances (PFAS)
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Immune System Effects: PFAS exposure disrupts hormone receptors in human cell cultures, with bioassays showing altered immune responses at concentrations as low as 0.5 μg/L .
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Cardiometabolic Risks: Epidemiological studies link PFAS to increased diabetes and cardiovascular disease risks, though causal mechanisms remain under investigation .
Chemical Mixtures
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Synergistic Toxicity: Office dust containing flame retardants and plasticizers exhibits 3–5× greater endocrine disruption than individual chemicals .
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Priority Contaminants: The model identifies perfluorinated compounds and dioxins as high-risk substances due to their persistence and bioaccumulation potential .
Pharmaceuticals in Water Systems
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Aquatic Toxicity: Propranolol and fluoxetine show lethal effects on zooplankton at 1 mg/L and 0.5 mg/L, respectively .
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Human Health Gaps: No conclusive evidence links environmental drug residues to acute human toxicity, but chronic exposure risks are unstudied .
Nanomaterials and Disinfection Byproducts
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Carcinogenicity: Trihalomethanes (THMs) in drinking water correlate with bladder cancer (OR = 1.4–1.6) .
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Nanoparticle Risks: Titanium dioxide and carbon nanotubes induce oxidative stress in lung cells at occupational exposure levels .
Limitations and Future Directions
Product Specs
Product Science Overview
The Impact RWD Domain Protein, also known as IMPACT or RWDD5, is a translational regulator protein that plays a crucial role in maintaining high levels of translation during amino acid starvation . It is classified under the RWD domain-containing proteins, which are characterized by their involvement in various cellular processes, including protein synthesis and regulation .
IMPACT is primarily involved in the regulation of protein synthesis. It interacts with GCN1/GCN1L1, preventing the activation of GCN2 protein kinases (EIF2AK1 to 4), which are responsible for the down-regulation of protein synthesis under stress conditions . By inhibiting GCN2 activation, IMPACT ensures continuous protein synthesis even during amino acid starvation . This function is particularly important in specific neuronal cells, where it may also facilitate neuritogenesis .
The mode of action of IMPACT involves its interaction with the GCN1/GCN1L1 complex. Under normal conditions, GCN2 kinases are activated by amino acid starvation, leading to the phosphorylation of eIF-2-alpha and subsequent down-regulation of protein synthesis . IMPACT impairs this process by binding to GCN1/GCN1L1, thereby preventing the activation of GCN2 and maintaining protein synthesis .
IMPACT’s regulatory mechanisms are closely tied to its role in translational control. By modulating the activity of GCN2 kinases, IMPACT plays a critical role in the cellular response to amino acid availability . This regulation is essential for maintaining cellular homeostasis and ensuring proper protein synthesis under varying nutritional conditions .
IMPACT is expressed in various tissues, with notable expression in the brain, including regions such as the hippocampus, amygdala, and cerebral cortex . It is localized to the nucleoplasm and exhibits general cytoplasmic and nuclear expression . The protein’s expression profile suggests its involvement in critical neuronal functions and its importance in maintaining cellular protein synthesis .
Human recombinant IMPACT protein is produced using various expression systems, including E. coli and HEK 293 cells . These recombinant proteins are used in research to study the protein’s function, interactions, and regulatory mechanisms. Recombinant IMPACT proteins are available with different tags, such as His and GST, to facilitate purification and detection .
