BackgroundApoptosis is an essential property of all higher organisms that involves extremely complex signaling pathways. Mathematical modeling provides a rigorous integrative approach for analyzing and understanding such intricate biological systems.ResultsHere, we constructed a large-scale, literature-based model of apoptosis pathways responding to an external stimulus, cisplatin. Our model includes the key elements of three apoptotic pathways induced by cisplatin: death receptor-mediated, mitochondrial, and endoplasmic reticulum-stress pathways. We showed that cisplatin-induced apoptosis had dose- and time-dependent characteristics, and the level of apoptosis was saturated at higher concentrations of cisplatin. Simulated results demonstrated that the effect of the mitochondrial pathway on apoptosis was the strongest of the three pathways. The cross-talk effect among pathways accounted for approximately 25% of the total apoptosis level.ConclusionsUsing this model, we revealed a novel mechanism by which cisplatin induces dose-dependent cell death. Our finding that the level of apoptosis was affected by not only cisplatin concentration, but also by cross talk among pathways provides in silico evidence for a functional impact of system-level characteristics of signaling pathways on apoptosis.

No abstract

Articles you may be interested inPersistent photoconductivity due to trapping of induced charges in Sn/ZnO thin film based UV photodetector Cadmium sulfide ͑CdS͒ thin films with n-type semiconductor characteristics were prepared at room temperature on glass substrates by radio-frequency magnetron sputtering for photoconductive-sensor applications. Films deposited at room temperature exhibit polycrystalline phases and show smooth surface morphologies. The deposition rate of the films decreases with increasing working pressure. The dark-and photoresistances in 400-nm-thick CdS films deposited at 6.7ϫ 10 −1 Pa and 80 W were approximately 1 ϫ 10 5 and 3 ϫ 10 4 ⍀ / sq, respectively. Lowering both the dark-and photoresistances lowers the sensitivity ͑R dark / R photo ͒ of the resistance.

No abstract

Results on the optical characterisation of copper deep acceptors throughout the alloy composition range (0 < x < 1) of GaAs, -,P, are reported. A comparison of the hole photoionisation spectra for different compositions, measured by the transient photocapacitance technique. reveals a broadening effect near the threshold which is interpreted in terms of random alloy effects on the deep level. An approximately linear variation of the hole photoionisation threshold with composition is found.t O n sabbatical leave from and permanent address: