10,424 research outputs found
Exploring emergent properties in cellular homeostasis using OnGuard to model K+ and other ion transport in guard cells
It is widely recognized that the nature and characteristics of transport across eukaryotic membranes are so complex as to defy intuitive understanding. In these circumstances, quantitative mathematical modeling is an essential tool, both to integrate detailed knowledge of individual transporters and to extract the properties emergent from their interactions. As the first, fully integrated and quantitative modeling environment for the study of ion transport dynamics in a plant cell, OnGuard offers a unique tool for exploring homeostatic properties emerging from the interactions of ion transport, both at the plasma membrane and tonoplast in the guard cell. OnGuard has already yielded detail sufficient to guide phenotypic and mutational studies, and it represents a key step toward ‘reverse engineering’ of stomatal guard cell physiology, based on rational design and testing in simulation, to improve water use efficiency and carbon assimilation. Its construction from the HoTSig libraries enables translation of the software to other cell types, including growing root hairs and pollen. The problems inherent to transport are nonetheless challenging, and are compounded for those unfamiliar with conceptual ‘mindset’ of the modeler. Here we set out guidelines for the use of OnGuard and outline a standardized approach that will enable users to advance quickly to its application both in the classroom and laboratory. We also highlight the uncanny and emergent property of OnGuard models to reproduce the ‘communication’ evident between the plasma membrane and tonoplast of the guard cell
Spatial fluctuations at vertices of epithelial layers: quantification of regulation by Rho pathway
In living matter, shape fluctuations induced by acto-myosin are usually
studied in vitro via reconstituted gels, whose properties are controlled by
changing the concentrations of actin, myosin and cross-linkers. Such an
approach deliberately avoids to consider the complexity of biochemical
signaling inherent to living systems. Acto-myosin activity inside living cells
is mainly regulated by the Rho signaling pathway which is composed of multiple
layers of coupled activators and inhibitors. We investigate how such a pathway
controls the dynamics of confluent epithelial tissues by tracking the
displacements of the junction points between cells. Using a phenomenological
model to analyze the vertex fluctuations, we rationalize the effects of
different Rho signaling targets on the emergent tissue activity by quantifying
the effective diffusion coefficient, the persistence time and persistence
length of the fluctuations. Our results reveal an unanticipated correlation
between layers of activation/inhibition and spatial fluctuations within
tissues. Overall, this work connects the regulation via biochemical signaling
with mesoscopic spatial fluctuations, with potential application to the study
of structural rearrangements in epithelial tissues.Comment: 8 pages, 3 figure
The Origins of Computational Mechanics: A Brief Intellectual History and Several Clarifications
The principle goal of computational mechanics is to define pattern and
structure so that the organization of complex systems can be detected and
quantified. Computational mechanics developed from efforts in the 1970s and
early 1980s to identify strange attractors as the mechanism driving weak fluid
turbulence via the method of reconstructing attractor geometry from measurement
time series and in the mid-1980s to estimate equations of motion directly from
complex time series. In providing a mathematical and operational definition of
structure it addressed weaknesses of these early approaches to discovering
patterns in natural systems.
Since then, computational mechanics has led to a range of results from
theoretical physics and nonlinear mathematics to diverse applications---from
closed-form analysis of Markov and non-Markov stochastic processes that are
ergodic or nonergodic and their measures of information and intrinsic
computation to complex materials and deterministic chaos and intelligence in
Maxwellian demons to quantum compression of classical processes and the
evolution of computation and language.
This brief review clarifies several misunderstandings and addresses concerns
recently raised regarding early works in the field (1980s). We show that
misguided evaluations of the contributions of computational mechanics are
groundless and stem from a lack of familiarity with its basic goals and from a
failure to consider its historical context. For all practical purposes, its
modern methods and results largely supersede the early works. This not only
renders recent criticism moot and shows the solid ground on which computational
mechanics stands but, most importantly, shows the significant progress achieved
over three decades and points to the many intriguing and outstanding challenges
in understanding the computational nature of complex dynamic systems.Comment: 11 pages, 123 citations;
http://csc.ucdavis.edu/~cmg/compmech/pubs/cmr.ht
Neural Models of Normal and Abnormal Behavior: What Do Schizophrenia, Parkinsonism, Attention Deficit Disorder, and Depression Have in Common?
Defense Advanced Research Projects Agency and Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333
Synthetic biology—putting engineering into biology
Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis—synthetic biology’s system fabrication process—supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.
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