An integrative, multi-scale, genome-wide model reveals the phenotypic landscape of Escherichia coli.

Given the vast behavioral repertoire and biological complexity of even the simplest organisms, accurately predicting phenotypes in novel environments and unveiling their biological organization is a challenging endeavor. Here, we present an integrative modeling methodology that unifies under a common framework the various biological processes and their interactions across multiple layers. We trained this methodology on an extensive normalized compendium for the gram-negative bacterium Escherichia coli, which incorporates gene expression data for genetic and environmental perturbations, transcriptional regulation, signal transduction, and metabolic pathways, as well as growth measurements. Comparison with measured growth and high-throughput data demonstrates the enhanced ability of the integrative model to predict phenotypic outcomes in various environmental and genetic conditions, even in cases where their underlying functions are under-represented in the training set. This work paves the way toward integrative techniques that extract knowledge from a variety of biological data to achieve more than the sum of their parts in the context of prediction, analysis, and redesign of biological systems

Age structure landscapes emerge from the equilibrium between aging and rejuvenation in bacterial populations.

The physiological asymmetry between daughters of a mother bacterium is produced by the inheritance of either old poles, carrying non-genetic damage, or newly synthesized poles. However, as bacteria display long-term growth stability leading to physiological immortality, there is controversy on whether asymmetry corresponds to aging. Here we show that deterministic age structure landscapes emerge from physiologically immortal bacterial lineages. Through single-cell microscopy and microfluidic techniques, we demonstrate that aging and rejuvenating bacterial lineages reach two distinct states of growth equilibria. These equilibria display stabilizing properties, which we quantified according to the compensatory trajectories of continuous lineages throughout generations. Finally, we show that the physiological asymmetry between aging and rejuvenating lineages produces complex age structure landscapes, resulting in a deterministic phenotypic heterogeneity that is neither an artifact of starvation nor a product of extrinsic damage. These findings indicate that physiological immortality and cellular aging can both be manifested in single celled organisms

Phase lagging model of brain response to external stimuli - modeling of single action potential

In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions where the results can be verified against the real EEG signal.Comment: 19 page

Space Station Freedom ECLSS: A step toward autonomous regenerative life support systems

The Environmental Control and Life Support System (ECLSS) is a Freedom Station distributed system with inherent applicability to extensive automation primarily due to its comparatively long control system latencies. These allow longer contemplation times in which to form a more intelligent control strategy and to prevent and diagnose faults. The regenerative nature of the Space Station Freedom ECLSS will contribute closed loop complexities never before encountered in life support systems. A study to determine ECLSS automation approaches has been completed. The ECLSS baseline software and system processes could be augmented with more advanced fault management and regenerative control systems for a more autonomous evolutionary system, as well as serving as a firm foundation for future regenerative life support systems. Emerging advanced software technology and tools can be successfully applied to fault management, but a fully automated life support system will require research and development of regenerative control systems and models. The baseline Environmental Control and Life Support System utilizes ground tests in development of batch chemical and microbial control processes. Long duration regenerative life support systems will require more active chemical and microbial feedback control systems which, in turn, will require advancements in regenerative life support models and tools. These models can be verified using ground and on orbit life support test and operational data, and used in the engineering analysis of proposed intelligent instrumentation feedback and flexible process control technologies for future autonomous regenerative life support systems, including the evolutionary Space Station Freedom ECLSS

KPP reaction-diffusion systems with loss inside a cylinder: convergence toward the problem with Robin boundary conditions

We consider in this paper a reaction-diffusion system under a KPP hypothesis in a cylindrical domain in the presence of a shear flow. Such systems arise in predator-prey models as well as in combustion models with heat losses. Similarly to the single equation case, the existence of a minimal speed c* and of traveling front solutions for every speed c > c* has been shown both in the cases of heat losses distributed inside the domain or on the boundary. Here, we deal with the accordance between the two models by choosing heat losses inside the domain which tend to a Dirac mass located on the boundary. First, using the characterizations of the corresponding minimal speeds, we will see that they converge to the minimal speed of the limiting problem. Then, we will take interest in the convergence of the traveling front solutions of our reaction-diffusion systems. We will show the convergence under some assumptions on those solutions, which in particular can be satisfied in dimension 2

Helicase on DNA: A Phase coexistence based mechanism

We propose a phase coexistence based mechanism for activity of helicases, ubiquitous enzymes that unwind double stranded DNA. The helicase-DNA complex constitutes a fixed-stretch ensemble that entails a coexistence of domains of zipped and unzipped phases of DNA, separated by a domain wall. The motor action of the helicase leads to a change in the position of the fixed constraint thereby shifting the domain wall on dsDNA. We associate this off-equilibrium domain wall motion with the unzipping activity of helicase. We show that this proposal gives a clear and consistent explanation of the main observed features of helicases.Comment: Revtex4. 5 pages. 4 figures. Published versio

Cell Migration with Multiple Pseudopodia: Temporal and Spatial Sensing Models

Cell migration triggered by pseudopodia (or “false feet”) is the most used method of locomotion. A 3D finite element model of a cell migrating over a 2D substrate is proposed, with a particular focus on the mechanical aspects of the biological phenomenon. The decomposition of the deformation gradient is used to reproduce the cyclic phases of protrusion and contraction of the cell, which are tightly synchronized with the adhesion forces at the back and at the front of the cell, respectively. First, a steady active deformation is considered to show the ability of the cell to simultaneously initiate multiple pseudopodia. Here, randomness is considered as a key aspect, which controls both the direction and the amplitude of the false feet. Second, the migration process is described through two different strategies: the temporal and the spatial sensing models. In the temporal model, the cell “sniffs” the surroundings by extending several pseudopodia and only the one that receives a positive input will become the new leading edge, while the others retract. In the spatial model instead, the cell senses the external sources at different spots of the membrane and only protrudes one pseudopod in the direction of the most attractive one