1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/596B270197FE27DE5FABB598B6210622/S0025557200150892a.pdf/div-class-title-span-class-italic-the-geometry-of-biological-time-span-by-a-t-winfree-pp-544-dm68-corrected-second-printing-1990-isbn-3-540-52528-9-springer-div.pdf

The geometry of biological time , by A. T. Winfree. Pp 544. DM68. Corrected Second Printing 1990. ISBN 3-540-52528-9 (Springer)

The spatiotemporal expression of genes in an organism is determined by regulatory systems that involve a large number of genes connected through a complex network of interactions. As an intuitive understanding of the behavior of these systems is hard to obtain, computer tools for the modeling and simulation of genetic regulatory networks will be indispensable. This report reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, ordinary and partial differential equations, stochastic equations, Boolean networks and their generalizations, qualitative differential equations, and rule-based formalisms. In addition, the report discusses how these formalisms have been used in the modeling and simulation of regulatory systems.

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Modeling and simulation of genetic regulatory systems: a literature review.

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.

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Extracellular Matrix Degradation and Remodeling in Development and Disease

In the adult human, mesenchymal stem cells (MSCs) resident in bone marrow retain the capacity to proliferate and differentiate along multiple connective tissue lineages, including cartilage. In this study, culture-expanded human MSCs (hMSCs) of 60 human donors were induced to express the morphology and gene products of chondrocytes. Chondrogenesis was induced by culturing hMSCs in micromass pellets in the presence of a defined medium that included 100 nM dexamethasone and 10 ng/ml transforming growth factor-beta(3) (TGF-beta(3)). Within 14 days, cells secreted an extracellular matrix incorporating type II collagen, aggrecan, and anionic proteoglycans. hMSCs could be further differentiated to the hypertrophic state by the addition of 50 nM thyroxine, the withdrawal of TGF-beta(3), and the reduction of dexamethasone concentration to 1 nM. Increased understanding of the induction of chondrogenic differentiation should lead to further progress in defining the mechanisms responsible for the generation of cartilaginous tissues, their maintenance, and their regeneration.

Chondrogenic Differentiation of Cultured Human Mesenchymal Stem Cells from Marrow

To gain performance, developers often build scientific applications in procedural languages, such as C or Fortran, which unfortunately reduces flexibility. To address this imbalance, the authors present CompuCell3D, a multitiered, flexible, and scalable problem-solving environment for morphogenesis simulations that's written in C++ using object-oriented design patterns.

From Genes to Organisms Via the Cell: A Problem-Solving Environment for Multicellular Development

During vertebrate limb development, various genes of the Hox family, the products of which influence skeletal element identity, are expressed in specific spatiotemporal patterns in the limb bud mesenchyme. At the same time, the cells also exhibit ‘self-organizing’ behavior – interacting with each other via extracellular matrix and cell-cell adhesive molecules to form the arrays of mesenchymal condensations that lead to the cartilaginous skeletal primordia. A recent study by Yokouchi et al.(1) establishes a connection between these phenomena. They misexpressed the product of the Hoxa-13 gene in chick limb buds and demonstrated both skeletal pattern perturbations and changes in cell-cell adhesivity in mesenchyme aberrantly expressing this protein.

Sticky fingers: Hox genes and cell adhesion in vertebrate limb development.

Dynamical systems in which geometrically extended model cells produce and interact with diffusible (morphogen) and nondiffusible (extracellular matrix) chemical fields have proved very useful as models for developmental processes. The embryonic vertebrate limb is an apt system for such mathematical and computational modeling since it has been the subject of hundreds of experimental studies, and its normal and variant morphologies and spatiotemporal organization of expressed genes are well known. Because of its stereotypical proximodistally generated increase in the number of parallel skeletal elements, the limb lends itself to being modeled by Turing-type systems which are capable of producing periodic, or quasiperiodic, arrangements of spot- and stripe-like elements. This chapter describes several such models, including, (i) a system of partial differential equations in which changing cell density enters into the dynamics explicitly, (ii) a model for morphogen dynamics alone, derived from the latter system in the "morphostatic limit" where cell movement relaxes on a much slower time-scale than cell differentiation, (iii) a discrete stochastic model for the simplified pattern formation that occurs when limb cells are placed in planar culture, and (iv) several hybrid models in which continuum morphogen systems interact with cells represented as energy-minimizing mesoscopic entities. Progress in devising computational methods for handling 3D, multiscale, multimodel simulations of organogenesis is discussed, as well as for simulating reaction-diffusion dynamics in domains of irregular shape.

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Multiscale Models for Vertebrate Limb Development

During the process of matrix-driven translocation, certain types of cells or polystyrene latex beads are transported between compositionally different regions of a collagen matrix. Under appropriate conditions this translocation depends on an interaction between the cell or particle surface and fibronectin. We now show that this interaction takes place at a site located within the first 31 kDa of the amino-terminal end of the fibronectin molecule. Using defined fibronectin fragments and monoclonal antibodies directed against specific fibronectin domains, this site is established as both necessary and sufficient for the promotion of matrix-driven translocation. Competition experiments using heparin, heparan sulfate, and other sulfated polysaccharides show that this fibronectin site interacts with heparin-like cell or particle surface components in promoting matrix-driven translocation. Treatment of cells with heparinase renders them unresponsive to the translocational effect. An antibody directed against the amino-terminal domain of fibronectin completely inhibits matrix-driven translocation without interfering with heparin binding, suggesting that a post-binding conformational change in fibronectin may be required for promotion of the effect.

Matrix-driven translocation: dependence on interaction of amino-terminal domain of fibronectin with heparin-like surface components of cells or particles

Stuart A. Newman

Papers

From Genes to Organisms Via the Cell: A Problem-Solving Environment for Multicellular Development

Sticky fingers: Hox genes and cell adhesion in vertebrate limb development.

Multiscale Models for Vertebrate Limb Development

Matrix-driven translocation: dependence on interaction of amino-terminal domain of fibronectin with heparin-like surface components of cells or particles

Origination of Organismal Form