Asymmetric stochastic switching driven by intrinsic molecular noise

Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

Growth factor- and cytokine-driven pathways governing liver stemness and differentiation.

Liver is unique in its capacity to regenerate in response to injury or tissue loss. Hepatocytes and other liver cells are able to proliferate and repopulate the liver. However, when this response is impaired, the contribution of hepatic progenitors becomes very relevant. Here, we present an update of recent studies on growth factors and cytokine-driven intracellular pathways that govern liver stem/progenitor cell expansion and differentiation, and the relevance of these signals in liver development, regeneration and carcinogenesis. Tyrosine kinase receptor signaling, in particular, c-Met, epidermal growth factor receptors or fibroblast growth factor receptors, contribute to proliferation, survival and differentiation of liver stem/progenitor cells. Different evidence suggests a dual role for the transforming growth factor (TGF)-β signaling pathway in liver stemness and differentiation. On the one hand, TGF-β mediates progression of differentiation from a progenitor stage, but on the other hand, it contributes to the expansion of liver stem cells. Hedgehog family ligands are necessary to promote hepatoblast proliferation but need to be shut off to permit subsequent hepatoblast differentiation. In the same line, the Wnt family and β-catenin/T-cell factor pathway is clearly involved in the maintenance of liver stemness phenotype, and its repression is necessary for liver differentiation during development. Collectively, data indicate that liver stem/progenitor cells follow their own rules and regulations. The same signals that are essential for their activation, expansion and differentiation are good candidates to contribute, under adequate conditions, to the paradigm of transformation from a pro-regenerative to a pro-tumorigenic role. From a clinical perspective, this is a fundamental issue for liver stem/progenitor cell-based therapies.

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Peer-reviewed

Chaotic dynamics of electric-field domains in periodically driven superlattices

Self-sustained time-dependent current oscillations under dc voltage bias have been observed in recent experiments on n-doped semiconductor superlattices with sequential resonant tunneling. The current oscillations are caused by the motion and recycling of the domain wall separating low- and high-electric-field regions of the superlattice, as the analysis of a discrete drift model shows and experimental evidence supports. Numerical simulation shows that different nonlinear dynamical regimes of the domain wall appear when an external microwave signal is superimposed on the dc bias and its driving frequency and driving amplitude vary. On the frequency-amplitude parameter plane, there are regions of entrainment and quasiperiodicity forming Arnold tongues. Chaos is demonstrated to appear at the boundaries of the tongues and in the regions where they overlap. Coexistence of up to four electric-field domains randomly nucleated in space is detected under ac+dc driving.

Multifractal dimension of chaotic attractors in a driven semiconductor superlattice

The multifractal dimension of chaotic attractors has been studied in a weakly coupled superlattice driven by an incommensurate sinusoidal voltage as a function of the driving voltage amplitude. The derived multifractal dimension for the observed bifurcation sequence shows different characteristics for chaotic, quasiperiodic, and frequency-locked attractors. In the chaotic regime, strange attractors are observed. Even in the quasiperiodic regime, attractors with a certain degree of strangeness may exist. From the observed multifractal dimensions, the deterministic nature of the chaotic oscillations is clearly identified.

The dynamics of biofilm bacterial communities is driven by flow wax and wane in a temporary stream

Biofilm communities are exposed to long periods of desiccation in temporary streams. We investigated how water flow intermittency affected the bacterial community structure colonizing three different streambed compartments in a Mediterranean stream. Massive parallel sequencing revealed different bacterial communities in biofilms from sand sediments and cobbles. Bacterial communities were similar (62% of shared operational taxonomic units) in the epipsammic and hyporheic biofilms, and more diverse than those in the epilithic biofilms. The non-flow phase caused a decrease of bacterial diversity in the biofilms, when communities included only bacterial taxa assumed to be adapted to water stress. The most sensitive bacterial communities to flow intermittency were in the epilithic, where the exposure to physical stress was the highest. In sand sediments a wide group of bacterial taxa was tolerant to desiccation. During non-flow the proliferation of opportunistic taxa in the superficial compartments evidenced the biological link with the terrestrial environment. Bacterial communities better tolerate rewetting than desiccation, since a major number of taxa tolerant to rewetting occurred in all biofilms. Overall, bacterial communities in sandy compartments showed higher resistance to flow intermittency than those in epilithic biofilms

Comparison of a deterministic and a data driven model to describe MBR fouling

Membrane bioreactors (MBRs) are a combination of activated sludge bioreactors and membrane filtration, enabling high quality effluent with a small footprint. However, they can be beset by fouling, which causes an increase in transmembrane pressure (TMP). Modelling and simulation of changes in TMP could be useful to describe fouling through the identification of the most relevant operating conditions. Using experimental data from a MBR pilot plant operated for 462days, two different models were developed: a deterministic model using activated sludge model n°2d (ASM2d) for the biological component and a resistance in-series model for the filtration component as well as a data-driven model based on multivariable regressions. Once validated, these models were used to describe membrane fouling (as changes in TMP over time) under different operating conditions. The deterministic model performed better at higher temperatures (>20°C), constant operating conditions (DO set-point, membrane air-flow, pH and ORP), and high mixed liquor suspended solids (>6.9gL-1) and flux changes. At low pH (<7) or periods with higher pH changes, the data-driven model was more accurate. Changes in the DO set-point of the aerobic reactor that affected the TMP were also better described by the data-driven model. By combining the use of both models, a better description of fouling can be achieved under different operating conditions