Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Mathematical modeling of the dynamic storage of iron in ferritin

<p>Abstract</p> <p>Background</p> <p>Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content.</p> <p>Results</p> <p>Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated <it>in vitro </it>with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded.</p> <p>Conclusions</p> <p>The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.</p

A dimensional summation account of polymorphous category learning

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Data and code availaibility: The data and code for all analyses for all experiments are available at the OSF addresses given in each Results section. The stimuli are available at the same locations.Polymorphous concepts are hard to learn, and this is perhaps surprising because they, like many natural concepts, have an overall similarity structure. However, the dimensional summation hypothesis (Milton & Wills, 2004) predicts this difficulty. It also makes a number of other predictions about polymorphous concept formation, which are tested here. In Experiment 1 we confirm the theory’s prediction that polymorphous concept formation should be facilitated by deterministic pretraining on the constituent features of the stimulus. This facilitation is relative to an equivalent amount of training on the polymorphous concept itself. In Experiments 2–4, the dimensional summation account of this single feature pretraining effect is contrasted with some other accounts, including a more general strategic account (Experiment 2), seriality of training and stimulus decomposition accounts (Experiment 3), and the role of errors (Experiment 4). The dimensional summation hypothesis provides the best account of these data. In Experiment 5, a further prediction is confirmed — the single feature pretraining effect is eliminated by a concurrent counting task. The current experiments suggest the hypothesis that natural concepts might be acquired by the deliberate serial summation of evidence. This idea has testable implications for classroom learning.Biotechnology and Biological Sciences Research Council (BBSRC

Bioaccessibility of selenium after human ingestion in relation to its chemical species and compartmentalization in maize

International audienceSelenium is a micronutrient needed by all living organisms including humans, but often present in low concentration in food with possible deficiency. From another side, at higher concentrations in soils as observed in seleniferous regions of the world, and in function of its chemical species, Se can also induce (eco)toxicity. Root Se uptake was therefore studied in function of its initial form for maize (Zea mays L.), a plant widely cultivated for human and animal food over the world. Se phytotoxicity and compartmentalization were studied in different aerial plant tissues. For the first time, Se oral human bioaccessibility after ingestion was assessed for the main Se species (SeIV and SeVI) with the BARGE ex vivo test in maize seeds (consumed by humans), and in stems and leaves consumed by animals. Corn seedlings were cultivated in hydroponic conditions supplemented with 1 mg L−1 of selenium (SeIV, SeVI, Control) for 4 months. Biomass, Se concentration, and bioaccessibility were measured on harvested plants. A reduction in plant biomass was observed under Se treatments compared to control, suggesting its phytotoxicity. This plant biomass reduction was higher for selenite species than selenate, and seed was the main affected compartment compared to control. Selenium compartmentalization study showed that for selenate species, a preferential accumulation was observed in leaves, whereas selenite translocation was very limited toward maize aerial parts, except in the seeds where selenite concentrations are generally high. Selenium oral bioaccessibility after ingestion fluctuated from 49 to 89 % according to the considered plant tissue and Se species. Whatever the tissue, selenate appeared as the most human bioaccessible form. A potential Se toxicity was highlighted for people living in seleniferous regions, this risk being enhanced by the high Se bioaccessibility

Dogs and humans respond to emotionally competent stimuli by producing different facial actions

The commonality of facial expressions of emotion has been studied in different species since Darwin, with most of the research focusing on closely related primate species. However, it is unclear to what extent there exists common facial expression in species more phylogenetically distant, but sharing a need for common interspecific emotional understanding. Here we used the objective, anatomically-based tools, FACS and DogFACS (Facial Action Coding Systems), to quantify and compare human and domestic dog facial expressions in response to emotionally-competent stimuli associated with different categories of emotional arousal. We sought to answer two questions: Firstly, do dogs display specific discriminatory facial movements in response to different categories of emotional stimuli? Secondly, do dogs display similar facial movements to humans when reacting in emotionally comparable contexts? We found that dogs displayed distinctive facial actions depending on the category of stimuli. However, dogs produced different facial movements to humans in comparable states of emotional arousal. These results refute the commonality of emotional expression across mammals, since dogs do not display human-like facial expressions. Given the unique interspecific relationship between dogs and humans, two highly social but evolutionarily distant species sharing a common environment, these findings give new insight into the origin of emotion expression

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans

The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz), spontaneous fluctuations of the blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the “default” system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions) that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions) critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in the temporal and spatial brain functional networks of the human brain that underlie spontaneous neuronal dynamics, which provides important implications for our understanding of how intrinsically coherent spontaneous brain activity has evolved into an optimal neuronal architecture to support global computation and information integration in the absence of specific stimuli or behaviors

How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations