Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype

Responses of four Australian tree species to toxic concentrations of copper in solution culture

In Australia, metal-contaminated sites, including those with elevated levels of copper (Cu), are frequently revegetated with endemic plants. Little is known about the responses of Australian plants to excess Cu. Acacia holosericea, Eucalyptus crebra, Eucalyptus camaldulensis, and Melaleuca leucadendra were grown in solution culture with six Cu treatments (0.1 to 40 mu M). While A. holosericea was the most tolerant to excess Cu, all of the species tested were sensitive to excess Cu when compared with exotic tree and agricultural species. The critical external concentrations for toxicity were < 0.7 mu M for all species tested. There was little differentiation between shoot-tissue Cu concentrations in normal versus treated plants, thus, the derivation of critical shoot concentrations was possible only for the most tolerant species, A. holosericea. Critical root Cu concentrations were approximately 210 mu g g(-1) (A. holosericea), 150 mu g g(-1) (E. crebra), 25 mu g g(-1) (E. camaldulensis), and 165 mu g g(-1) (M. leucadendra). These results provide the first comprehensive combination of growth responses, critical concentrations, and toxicity symptoms for three important Australian genera for use in the management of Cu-contaminated sites

Differential effects of working memory load on priming and recognition of real images

Several studies have explored the effects of divided attention on priming, but little is known about the impact of working memory load on implicit visual memory. The aim of this study was to determine whether there are differential effects of working memory load on a visual priming task compared to a recognition task. In the encoding phase, participants were presented with real-object pictures and asked to classify them semantically. At retrieval, 40 studied and 40 new images were presented (partially masked) for 100 ms, and participants had to identify the object. Each trial was immediately followed by a recognition test, in which the unmasked image was shown again, and participants had to indicate whether it had been presented at encoding or not. Regarding working memory load, participants performed a task in which a load was imposed in half of the trials. Twenty-four participants concurrently performed an articulatory suppression task, another group of 24 subjects performed an executive demanding task, and a third group of 24 participants performed a spatial tapping task. Working memory load failed to diminish performance on both priming and recognition tests in the articulatory suppression condition. However, the backward counting and the tapping tasks influenced recognition, rather than priming. The relative pattern of backward counting effects on recognition and priming were then broadly replicated in a follow-up experiment using an adapted priming task (N = 24). Results suggest that a concurrent load has a more robust effect on recognition than on priming, especially when the working memory task is executively demanding

Not all identification tasks are born equal: testing the involvement of production processes in perceptual identification and lexical decision

The distinction between identification and production processes suggests that implicit memory should require more attention resources when there is a competition between alternative solutions during the test phase. The present two experiments assessed this hypothesis by examining the effects of divided attention (DA) at encoding on the high- and low-response-competition versions of perceptual identification (Experiment 1) and lexical decision (Experiment 2). In both experiments, words presented in the high-response-competition condition had many orthographic neighbours and at least one higher-frequency neighbour, whereas words presented in the low-response-competition condition had few orthographic neighbours and no higher-frequency neighbour. Consistent with the predictions of the identification/production distinction, Experiment 1 showed that DA reduced repetition priming in the high-, but not in the low-response-competition version of perceptual identification; in contrast, DA had comparable effects in the two versions of lexical decision (Experiments 2). These findings provide the first experimental evidence in support of the hypothesis that perceptual identification, a task nominally based on identification processes, might involve a substantive production componen