Influencing the redox balance of pancreatic beta cells could be a promising strategy for the treatment of diabetes. Nuclear factor erythroid 2p45-related factor 2 (Nrf2) is present in beta cells and regulates numerous genes involved in antioxidant defense. As reactive oxygen species (ROS) are important for beta cell signaling but induce oxidative stress when present in excess, this study elucidates the influence of Nrf2-activating compounds on different kinds of ROS and correlates changes in redox balance to effects on mitochondrial function, insulin release, and cell viability. Acute glucose stimulation (15 mmol/L) of murine islet cells of C57Bl/6N mice affects ROS and redox status of the cells differently. Those ROS monitored by dihydroethidium, which detects superoxide radical anions, decrease. By contrast, oxidant status, monitored by dichlorodihydrofluorescein, as well as intracellular H2O2, increases. Glucolipotoxicity completely prevents these fast, glucose-mediated alterations and inhibits glucose-induced NAD(P)H production, mitochondrial hyperpolarization, and ATP synthesis. Oltipraz (10 μmol/L) or dimethyl fumarate (DMF, 50 μmol/L) leads to nuclear accumulation of Nrf2, restores mitochondrial activity and glucose-dependent ROS turnover, and antagonizes glucolipotoxicity-induced inhibition of insulin release and apoptosis. Importantly, these beneficial effects only occur when beta cells are challenged and damaged by high lipid and carbohydrate supply. At physiological conditions, insulin release is markedly reduced in response to both Nrf2 activators. This is not associated with severe impairment of glucose-induced mitochondrial hyperpolarization or a rise in apoptosis but coincides with altered ROS handling. In conclusion, Nrf2 activators protect beta cells against glucolipotoxicity by preserving mitochondrial function and redox balance. As our data show that this maintains glucose-stimulated insulin secretion, targeting Nrf2 might be suited to ameliorate progression of type 2 diabetes mellitus. By contrast, nonstressed beta cells do not benefit from Nrf2 activation, thus underlining the importance of physiological shifts in ROS homeostasis for the regulation of beta cell function.
Exploration and analysis of vast empirical data is a cornerstone of the development and assessment of driver assistance systems. A common challenge is to apply the domain specific knowledge to the (mechanised) data handling, pre-processing and analysis process. Ontologies can describe domain specific knowledge in a structured way that is manageable for both humans and algorithms. This paper outlines an architecture to support an ontology based analysis process for data stored in databases. Build on these concepts and architecture, a prototype that handles semantic data annotations is presented. Finally, the concept is demonstrated in a realistic example. The usage of exchangeable ontologies generally allows the adaption of presented methods for different domains.
The Pupillary Light Reflex (PLR) controls the amount of light entering the eye. This might protect the retina when exposed to laser radiation. Higher radiation power causes the pupil to close more and more rapidly. Using a 532 nm laser beam with radiation power between 100 pW and 100 µW causes the pupil diameter to decrease between 15.4 % to 42.4 %. The decrease starts after a latency period ranging from 160 ms to 300 ms. Contraction takes additional 360 ms to 1100 ms and is increasing with power. A duration of more than 600 ms passes before the pupil size reaches the minimum. The response varies with wavelength and it is shown, that the Spectral Luminous Efficiency Function can not be used to describe dependency.
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