Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights.

Protein synthesis rates are determined, at the translational level, by properties of the transcript's sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we propose transcript length as a further key determinant of translation efficiency.

Cooperative response and clustering: Consequences of membrane-mediated interactions among mechanosensitive channels.

Mechanosensitive channels are ion channels which act as cells' safety valves, opening when the osmotic pressure becomes too high and making cells avoid damage by releasing ions. They are found on the cellular membrane of a large number of organisms. They interact with each other by means of deformations they induce in the membrane.

Brief isoflurane anaesthesia affects differential gene expression, gene ontology and gene networks in rat brain.

Much is still unknown about the mechanisms of effects of even brief anaesthesia on the brain and previous studies have simply compared differential expression profiles with and without anaesthesia. We hypothesised that network analysis, in addition to the traditional differential gene expression and ontology analysis, would enable identification of the effects of anaesthesia on interactions between genes. Rats (n=10 per group) were randomised to anaesthesia with isoflurane in oxygen or oxygen only for 15min, and 6h later brains were removed.

Oxygen-Driven Tumour Growth Model: A Pathology-Relevant Mathematical Approach.

Xenografts--as simplified animal models of cancer-differ substantially in vasculature and stromal architecture when compared to clinical tumours. This makes mathematical model-based predictions of clinical outcome challenging. Our objective is to further understand differences in tumour progression and physiology between animal models and the clinic.

Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans.

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.

High-resolution replication profiles define the stochastic nature of genome replication initiation and termination.

Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time.

The dynamics of genome replication using deep sequencing.

Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number during a synchronous S-phase allowed the precise determination of genome replication.

Stochastic association of neighboring replicons creates replication factories in budding yeast.

Inside the nucleus, DNA replication is organized at discrete sites called replication factories, consisting of DNA polymerases and other replication proteins. Replication factories play important roles in coordinating replication and in responding to replication stress. However, it remains unknown how replicons are organized for processing at each replication factory.

Integrated stress response of Escherichia coli to methylglyoxal: transcriptional readthrough from the nemRA operon enhances protection through increased expression of glyoxalase I.

Methylglyoxal (MG) elicits activation of K(+) efflux systems to protect cells against the toxicity of the electrophile. ChIP-chip targeting RNA polymerase, supported by a range of other biochemical measurements and mutant creation, was used to identify genes transcribed in response to MG and which complement this rapid response. The SOS DNA repair regulon is induced at cytotoxic levels of MG, even when exposure to MG is transient.

A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi.

Background: Saccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation.

Combinatorial stresses kill pathogenic Candida species.

Pathogenic microbes exist in dynamic niches and have evolved robust adaptive responses to promote survival in their hosts. The major fungal pathogens of humans, Candida albicans and Candida glabrata, are exposed to a range of environmental stresses in their hosts including osmotic, oxidative and nitrosative stresses. Significant efforts have been devoted to the characterization of the adaptive responses to each of these stresses.

Optimal placement of origins for DNA replication.

DNA replication is an essential process in biology and its timing must be robust so that cells can divide properly. Random fluctuations in the formation of replication starting points, called origins, and the subsequent activation of proteins lead to variations in the replication time. We analyze these stochastic properties of DNA and derive the positions of origins corresponding to the minimum replication time.

Reacting particles in open chaotic flows.

We study the collision probability p of particles advected by open flows with chaotic advection. We show that p scales with the particle size (or, alternatively, reaction distance) δ as a power law whose coefficient is determined by the fractal dimensions of the invariant sets defined by the advection dynamics. We also argue that this same scaling also holds for the reaction rate of active particles in the low-density regime.

Are the fractal skeletons the explanation for the narrowing of arteries due to cell trapping in a disturbed blood flow?

We show that common circulatory diseases, such as stenoses and aneurysms, generate chaotic advection of blood particles. This phenomenon has major consequences on the way the biochemical particles behave. Chaotic advection leads to a peculiar filamentary particle distribution, which in turn creates a favorable environment for particle reactions.

A matter of life or death: modeling DNA damage and repair in bacteria.

DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection between DNA repair and death is far from straightforward, and suggests that the repair mechanisms can be a double-edged sword.

Escape from attracting sets in randomly perturbed systems.

The dynamics of escape from an attractive state due to random perturbations is of central interest to many areas in science. Previous studies of escape in chaotic systems have rather focused on the case of unbounded noise, usually assumed to have Gaussian distribution. In this paper, we address the problem of escape induced by bounded noise.

Fractal structures in stenoses and aneurysms in blood vessels.

Recent advances in the field of chaotic advection provide the impetus to revisit the dynamics of particles transported by blood flow in the presence of vessel wall irregularities. The irregularity, being either a narrowing or expansion of the vessel, mimicking stenoses or aneurysms, generates abnormal flow patterns that lead to a peculiar filamentary distribution of advected particles, which, in the blood, would include platelets. Using a simple model, we show how the filamentary distribution depends on the size of the vessel wall irregularity, and how it varies under resting or exercise conditions.

Random fluctuation leads to forbidden escape of particles.

A great number of physical processes are described within the context of Hamiltonian scattering. Previous studies have rather been focused on trajectories starting outside invariant structures, since the ones starting inside are expected to stay trapped there forever. This is true though only for the deterministic case.

Mathematical modelling of whole chromosome replication.

All chromosomes must be completely replicated prior to cell division, a requirement that demands the activation of a sufficient number of appropriately distributed DNA replication origins. Here we investigate how the activity of multiple origins on each chromosome is coordinated to ensure successful replication. We present a stochastic model for whole chromosome replication where the dynamics are based upon the parameters of individual origins.

Emerging attractors and the transition from dissipative to conservative dynamics.

The topological structure of basin boundaries plays a fundamental role in the sensitivity to the final state in chaotic dynamical systems. Herewith we present a study on the dynamics of dissipative systems close to the Hamiltonian limit, emphasizing the increasing number of periodic attractors, and on the structural changes in their basin boundaries as the dissipation approaches zero. We show numerically that a power law with nontrivial exponent describes the growth of the total number of periodic attractors as the damping is decreased.

Transition to chaotic scattering: signatures in the differential cross section.

We show that bifurcations in chaotic scattering manifest themselves through the appearance of an infinitely fine-scale structure of singularities in the cross section. These "rainbow singularities" are created in a cascade, which is closely related to the bifurcation cascade undergone by the set of trapped orbits (the chaotic saddle). This cascade provides a signature in the differential cross section of the complex pattern of bifurcations of orbits underlying the transition to chaotic scattering.

Onset of chaotic advection in open flows.

In this paper we investigate the transition to chaos in the motion of particles advected by open flows with obstacles. By means of a topological argument, we show that the separation points on the surface of the obstacle imply the existence of a saddle point downstream from the obstacle, with an associated heteroclinic orbit. We argue that as soon as the flow becomes time periodic, these orbits give rise to heteroclinic tangles, causing passively advected particles to experience transient chaos.

Strange nonchaotic repellers.

We show the existence of strange nonchaotic repellers--that is, systems with transient dynamics whose nonattracting invariant set is fractal, but whose maximum Lyapunov coefficient is zero. We introduce the concept using a simple one-dimensional map and argue that strange nonchaotic repellers are a general phenomenon, occurring in bifurcation points of transient chaotic systems. All strange nonchaotic systems studied to date have been attractors; here, it is revealed that strange nonchaotic sets are also present in transient systems.

Signatures of fractal clustering of aerosols advected under gravity.

Aerosols under chaotic advection often approach a strange attractor. They move chaotically on this fractal set but, in the presence of gravity, they have a net vertical motion downwards. In practical situations, observational data may be available only at a given level, for example, at the ground level.

Traffic of particles in complex networks.

The study of the information flow through communication networks, such as the Internet, is of great importance. In the Internet, information flows in discrete units ("packets"), and the capacity of storage and processing of information of computers is finite. Thus if there are many packets walking on the network at the same time, they will interfere with each other.