Project description:REMOVAL OF ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF THE PESTICIDE METALDEHYDE FROM WATER IN BIOAUGMENTED PILOT-SCALE SLOW SAND FILTERS
Project description:Here we report on the development of novel polyimide-based flexible magnetic actuators for improving hydrocephalus shunts. The static and dynamic mechanical responses of the thin-film magnetic microdevices were quantitatively measured. The bacteria-removing capabilities of the microfabricated devices were also evaluated. Although additional evaluations are necessary, the preliminary results show promising potential for combatting bacteria-induced biofouling. Lastly, the thin-film microdevices are integrated into a single-pore silicone catheter to demonstrate a proof-of-concept, MEMS-enabled self-clearing, smart catheter.
Project description:Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. The persistence and widespread distribution of these compounds in humans have brought them under intense scrutiny. Limited pharmacokinetic data is available in humans; however, human data exists for two communities with drinking water contaminated by PFAAs. Also, there is toxicological and pharmacokinetic data for monkeys, which can be quite useful for cross-species extrapolation to humans. The goal of this research was to develop a physiologically-based pharmacokinetic (PBPK) model for PFOA and PFOS for monkeys and then scale this model to humans in order to describe available human drinking water data. The monkey model simulations were consistent with available PK data for monkeys. The monkey model was then extrapolated to the human and then used to successfully simulate the data collected from residents of two communities exposed to PFOA in drinking water. Human PFOS data is minimal; however, using the half-life estimated from occupational exposure, our model exhibits reasonable agreement with the available human serum PFOS data. It is envisioned that our PBPK model will be useful in supporting human health risk assessments for PFOA and PFOS by aiding in understanding of human pharmacokinetics.
Model is encoded by Ruby and submitted to BioModels by Ahmad Zyoud
Project description:Liver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks We used microarrays to detail the gene expression after drinking hydrogen water.
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular break and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular brake and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular brake and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.