The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.
Long data sets are one of the prime requirements of time series analysis techniques to unravel the dynamics of an underlying system. However, acquiring long data sets is often not possible. In this paper, we address the question of whether it is still possible to understand the complete dynamics of a system if only short (but many) time series are observed. The key idea is to generate a single long time series from these short segments using the concept of recurrences in phase space. This long time series is constructed so as to exhibit a dynamics similar to that of a long time series obtained from the corresponding underlying system.
We perform a systematic data analysis on high resolution (0.5-12 kHz) multiarray microelectrode recordings from an animal model of spontaneous limbic epilepsy, to investigate the role of high frequency oscillations and the occurrence of early precursors for seizures. Results of spectral analysis confirm the importance of very high frequency oscillations (even greater than 600 Hz) in normal (healthy) and abnormal (epileptic) hippocampus. Furthermore, we show that the measures of Recurrence Quantification Analysis (RQA) and Recurrence Time Statistics (RTS) are successful in indicating, rather uniquely, the onset of ictal state and the occurrence of some warnings/precursors during the pre-ictal state, in contrast to the linear measures investigated.
The lack of long enough data sets is a major problem in the study of many real world systems. As it has been recently shown [C. Komalapriya, M. Thiel, M. C. Romano, N. Marwan, U. Schwarz, and J. Kurths, Phys. Rev. E 78, 066217 (2008)], this problem can be overcome in the case of ergodic systems if an ensemble of short trajectories is available, from which dynamically reconstructed trajectories can be generated. However, this method has some disadvantages which hinder its applicability, such as the need for estimation of optimal parameters. Here, we propose a substantially improved algorithm that overcomes the problems encountered by the former one, allowing its automatic application. Furthermore, we show that the new algorithm not only reproduces the short term but also the long term dynamics of the system under study, in contrast to the former algorithm. To exemplify the potential of the new algorithm, we apply it to experimental data from electrochemical oscillators and also to analyze the well-known problem of transient chaotic trajectories.
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