Metabolism of iron and iron oxide nanoparticles in glial cells

Iron is an essential metal for mammalian cells catalyzing redox reactions in various metabolic pathways. However, iron can also induce cellular damage due to increased formation of reactive oxygen species (ROS). Among the different brain cell types, oligodendrocytes produce and maintain the myelin sheaths around neuronal axons whereas brain astrocytes participate in a variety of different brain functions such as synaptic signal transduction, regulation of metal homeostasis and detoxification of xenobiotics. In brain, these cells may encounter iron oxide nanoparticles (Fe-NP), since Fe-NP are extensively investigated for biomedical applications. This thesis investigated the metabolism of iron and Fe-NP in glial cells. The oligodendroglial OLN-93 cells express the mRNAs of the protein transferrin, transferrin-receptor and divalent metal transporter 1 for iron uptake as well as the iron storage protein ferritin. The proliferation of these cells depended on the availability of extracellular iron and can be inhibited by iron chelators. Furthermore, OLN-93 cells accumulated substantial amounts of iron from low molecular weight iron salts and Fe-NP. The cell viability was not compromised despite of high intracellular iron concentrations. Moreover, exposure to Fe-NP hardly affected the metabolism of OLN-93 cells. Intracellularly, iron was mobilized from Fe-NP by OLN-93 cells as demonstrated by the increase in proliferation following iron restriction, by the upregulation of ferritin and by the inhibition of Fe-NP-dependent ROS formation by a cell-membrane-permeable iron chelator. Also primary astrocytes took up Fe-NP as shown by increased cellular iron contents and electron microscopy. Both OLN-93 cells and astrocytes accumulated iron from Fe-NP in comparable amounts, showed similar time- and concentration-dependencies of iron accumulation and stored iron in ferritin. These observations suggest that the uptake and the cellular fate of Fe-NP are similar in OLN-93 cells and astrocytes

iOS Application to Track Student Driver Practice Hours

In order to obtain a driver’s license in the state of Indiana, a learner must submit a documented record of driving practice sessions totalling at least 50 hours total driving time. The state BMV provides the “Log of Supervised Driving Practice,” a PDF document that a learner can use to keep track of drives on paper. This process is streamlined through the development of an iPhone application. A driver can use the application to keep track of progress towards the required number of practice hours, and export a copy of the State of Indiana document, filled in with all logged trips, ready to print and sign. Additionally, the user can view and edit data about each drive, as well as add and delete trips manually. The application also supports multiple users on the same device, with each user having his or her own separate driving log. The development process involved an iterative, agile software development method, and modern iOS development tools and frameworks - the Swift programming language along with SwiftUI, a declarative framework for building user interfaces

Conceptual design of nuclear systems for hydrogen production

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2006.Includes bibliographical references (p. 77-81).Demand for hydrogen in the transportation energy sector is expected to keep growing in the coming decades; in the short term for refining heavy oils and in the long term for powering fuel cells. However, hydrogen cannot be harvested from natural sources like other fuels, it must be industrially produced. In the United States, the vast majority of hydrogen is produced today by reforming methane, a carbon-based fuel. Due to environmental and fuel source concerns, non-carbon alternatives for producing hydrogen from water are being explored using different combinations of thermal, chemical, and electrical energy. This work explores some of the non-carbon alternatives, specifically using a nuclear reactor for providing heat and electricity for high temperature steam electrolysis and a hybrid electrolysis-chemical sulfur cycle. Also addressed is the sensitivity of production and efficiency of these cycles to process conditions. For a desired hydrogen distribution pressure of 3MPa, high system pressures increase the efficiency of high temperature steam electrolysis because of the decreased post-cycle compression energy requirements. High system pressures for the hybrid sulfur cycle, however, decrease the equilibrium thermal acid decomposition necessary to the process. High temperature steam electrolysis may also be used to provide variable hydrogen production when coupled with an electricity generation system. Increased hydrogen production decreases the efficiency of the electricity production, because of the high enthalpy removed from the reactor system. Both approaches are also analyzed for their sensitivity to incomplete reactions within the process loop.by Katherine J. Hohnholt.S.B

Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD

Acknowledgements This work was supported by grants from the Biotechnology and Biological Science Research Council (BB/I007261/1 and BB/N002342/1) and The Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS 854/11).Peer reviewedPublisher PD

Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in a Xenopus laevis model.

Multicore superparamagnetic nanoparticles have been proposed as ideal tools for some biomedical applications because of their high magnetic moment per particle, high specific surface area and long term colloidal stability. Through controlled aggregation and packing of magnetic cores it is possible to obtain not only single-core but also multicore and hollow spheres with internal voids. In this work, we compare toxicological properties of single and multicore nanoparticles. Both types of particles showed moderate in vitro toxicity (MTT assay) tested in Hep G2 (human hepatocellular carcinoma) and Caco-2 (human colorectal adenocarcinoma) cells. The influence of surface chemistry in their biological behavior was also studied after functionalization with O,O′-bis(2-aminoethyl) PEG (2000 Da). For the first time, these nanoparticles were evaluated in a Xenopus laevis model studying their whole organism toxicity and their impact upon iron metabolism. The degree of activation of the metabolic pathway depends on the size and surface charge of the nanoparticles which determine their uptake. The results also highlight the potential of Xenopus laevis model bridging the gap between in vitro cell-based assays and rodent models for toxicity assessment to develop effective nanoparticles for biomedical applications

Metabolismus von Eisen und Eisenoxid-Nanopartikeln in Gliazellen

Iron is an essential metal for mammalian cells catalyzing redox reactions in various metabolic pathways. However, iron can also induce cellular damage due to increased formation of reactive oxygen species (ROS). Among the different brain cell types, oligodendrocytes produce and maintain the myelin sheaths around neuronal axons whereas brain astrocytes participate in a variety of different brain functions such as synaptic signal transduction, regulation of metal homeostasis and detoxification of xenobiotics. In brain, these cells may encounter iron oxide nanoparticles (Fe-NP), since Fe-NP are extensively investigated for biomedical applications. This thesis investigated the metabolism of iron and Fe-NP in glial cells. The oligodendroglial OLN-93 cells express the mRNAs of the protein transferrin, transferrin-receptor and divalent metal transporter 1 for iron uptake as well as the iron storage protein ferritin. The proliferation of these cells depended on the availability of extracellular iron and can be inhibited by iron chelators. Furthermore, OLN-93 cells accumulated substantial amounts of iron from low molecular weight iron salts and Fe-NP. The cell viability was not compromised despite of high intracellular iron concentrations. Moreover, exposure to Fe-NP hardly affected the metabolism of OLN-93 cells. Intracellularly, iron was mobilized from Fe-NP by OLN-93 cells as demonstrated by the increase in proliferation following iron restriction, by the upregulation of ferritin and by the inhibition of Fe-NP-dependent ROS formation by a cell-membrane-permeable iron chelator. Also primary astrocytes took up Fe-NP as shown by increased cellular iron contents and electron microscopy. Both OLN-93 cells and astrocytes accumulated iron from Fe-NP in comparable amounts, showed similar time- and concentration-dependencies of iron accumulation and stored iron in ferritin. These observations suggest that the uptake and the cellular fate of Fe-NP are similar in OLN-93 cells and astrocytes

Toward a just tax code

This paper examines the unjust nature of the tax code arguing that this is grounds for reform. Once justice is defined as impartial treatment, the tax code is clearly unjust in that individuals receive vastly different treatment. Consequently, the theoretical root of the tax code, Utilitarianism, is contrasted with Contractarianism, a theory that would limit government action that is partial to one group or another. The origin of justice and moral equivalency is described as a reason for equal tax treatment. Finally, a recommendation for the tax code is made that would meet the ideals of justice and moral equality

[3-13C]Pyruvate: Useful Alternative to labeled Glucose for in vitro Metabolic Studies in Primary Mouse Hepatocytes

The application of stable isotope labeling in cell culture experiments is a widely used and potent model for the study and characterization of metabolic pathways and fluxes. In particular, incorporation of 13C-labels at certain carbon positions of a given metabolite may not only provide important information about pathways and fluxes but may even reveal unexpected metabolic phenomena without prior knowledge. Depending on the cellular model and the area of interest, one has to take into consideration which labeled substrate will give the most valuable information. Primary hepatocytes in cell culture – a widely used model to study liver physiology and diseases – are expected to use a variety of substrates for their cellular and energy metabolism. So far, 13C-NMR studies have been rarely performed in isolated hepatocytes. Labeled glucose is the most widely used substrate in cells isolated from various organs. However, we have shown in preliminary experiments that hepatocytes in primary culture do not readily metabolize glucose taken up from the medium. Since hepatocytes have a very high mitochondrial activity, we have therefore decided to use one- and two-dimensional multinuclear NMR-spectroscopy to characterize the metabolism of [3-13C]pyruvate and the metabolic isotopomers derived trough various pathways in these cells

OPTIMIZATION OF THE HYBRID SULFUR CYCLE FOR HYDROGEN GENERATION

The hybrid sulfur cycle (modified from the Westinghouse Cycle) for decomposing water into oxygen and hydrogen is evaluated. Hydrogen is produced by electrolysis of sulfur dioxide and water mixture at low temperature, which also results in the formation of oxygen and sulfuric acid. The sulfuric acid is decomposed into steam and sulfur trioxide, which at high temperature (1100 K) is further decomposed into sulfur dioxide and oxygen. The presence of sulfur dioxide along with water in the electrolyzer reduces the required electrode potential well below that required for electrolysis of pure–water, thus reducing the total energy consumed by the electrolyzer. Further, using only sulfuric acid for the thermochemical processes minimizes the required chemical stock in the hydrogen plant well below that required for the sulfur–iodine pure thermochemical cycle (SI cycle). In this study, ways to optimize the energy efficiency of the hybrid cycle are explored by varying the electrolyzer acid concentration, decomposer acid concentration, pressure and temperature of the decomposer and internal heat recuperation, based on currently available experimental data for the electrode potential. An optimal cycle efficiency of 43.9% (LHV) appears to be achievable (5 bar, 1100 K and 60 mol–% of H[subscript 2]SO[subscript 4] at the decomposer, 70 w–% of H[subscript 2]SO[subscript 4] at the electrolyzer). However, the ideal cycle efficiency is over 70% (LHV), which leaves room to improve the achievable efficiency with further development. For a maximum temperature of 1200 K, 47% (LHV) appears to be the maximum achievable cycle efficiency (10 bar, 1200 K and 60 mol–% of H[subscript 2]SO[subscript 4] for decomposer, 70 w–% of H[subscript 2]SO[subscript 4] for electrolyzer). The ideal cycle efficiency is over 80% (LHV). Operation under elevated pressures (70 bar or higher) results in minimized equipment size and capital cost, but there is loss in thermal efficiency. However, the loss in efficiency as pressure increases is not large at high temperature (1200 K) compared to that at low temperatures (1000–1100 K). Therefore, high pressure operation would be favored only if we can achieve high temperature. The major factors that can affect the cycle efficiency are reducing the electrode over–potential and having structural materials that can accommodate operation at high temperature and high acid concentration.Korean Science and Engineering Foundation (Post–doctoral Fellowship

Metabolic Characterization of Patients with Alcohol and Non-Alcoholic Steatohepatitis

Liver steatosis is an increasingly common cause of liver diseases. Today it is still difficult to differentiate patients with non-alcoholic steatohepatitis (NASH) from patients with alcoholic steatohepatitis (ASH) on the basis of clinical and biochemical evaluations. Since it is becoming urgent to develop new diagnostic methods for NASH, we applied high-resolution 1H- and (natural abundance) 13C-NMR spectroscopy to detect metabolic profiles in preparations of blood and urine in patients with NASH and ASH. 1H- and 13C-NMR spectra of urine and blood samples showed considerable and reproducible differences in specific metabolites involved in intermediary as well as lipid metabolism in patients with NASH and ASH compared to healthy controls. The results demonstrate that NMR applications on human body fluids are of great potential to characterize NASH, a disease displaying multiple interrelated metabolic factors. This approach could provide noninvasively data to characterize steatosis and give the possibility to distinguish between NASH and ASH