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.

/pdf/modeling-and-simulation-of-genetic-regulatory-systems-a-2pgggkutcb.pdf

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.

/pdf/extracellular-matrix-degradation-and-remodeling-in-32jsm155da.pdf

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

The reliable dependence of many features of contemporary organisms on changes in gene content and activity is tied to the processes of Mendelian inheritance and Darwinian evolution. With regard to morphological characters, however, Mendelian inheritance is the exception rather than the rule, and neo-Darwinian mechanisms in any case do not account for the origination (as opposed to the inherited variation) of such characters. It is proposed, therefore, that multicellular organisms passed through a pre-Mendelian, pre-Darwinian phase, whereby cells, genes and gene products constituted complex systems with context-dependent, self-organizing morphogenetic capabilities. An example is provided of a plausible ’core’ mechanism for the development of the vertebrate limb that is both inherently pattern forming and morphogenetically plastic. It is suggested that most complex multicellular structures originated from such systems. The notion that genes are privileged determinants of biological characters can only be sustained by neglecting questions of evolutionary origination and the evolution of developmental mechanisms.

The pre-Mendelian, pre-Darwinian world: shifting relations between genetic and epigenetic mechanisms in early multicellular evolution.

On the basis of recent experimental results obtained using a model biological system, we argue that well-known physical phenomena like wetting and percolation may play a significant role in morphogenetic changes which occur during development. We also present results of scanning microscopy studies on the structure of the system, which support our theoretical conclusions.

Phase transition and morphogenesis in a model biological system

https://faculty.washington.edu/scottjdw/pdfs/zhang_dev_biol_1996_p51.pdf

Nuclear Localization of Type II cAMP-Dependent Protein Kinase during Limb Cartilage Differentiation Is Associated with a Novel Developmentally Regulated A-Kinase Anchoring Protein

/pdf/evolution-in-four-dimensions-genetic-epigenetic-behavioral-2wof3n8pn6.pdf

Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. Eva Jablonka and Marion Lamb.

The interaction of heparin with the NH2-terminal domain of human plasma fibronectin was studied by using matrix-driven translocation, an assay for the adhesion of extracellular macromolecules with cell or particle surfaces within artificial collagen matrices. Partial desulfation of heparin rendered it ineffective in competitively inhibiting the interaction of the fibronectin NH2-terminal domain with heparin-coated particles, suggesting a role for sulfate groups of heparin in the interaction. Analysis of the fibronectin domain in terms of its primary structure, its proposed organization into "type I modules", and its hydrophilic and flexible segments led to the identification of several arginine-containing sites of potential interaction with the sulfate groups of heparin. Modification of increasing numbers of arginine side chains with 1,2-cyclohexanedione under mild conditions eventually led to decreases in translocation-promoting activity, and of heparin binding capacity as measured in a gel-shift assay, but the major portions of these functions were retained even when the four most accessible arginines (attributed to sites in and adjacent to the large loops of the type I modules) were modified. With the modification of additional arginines (attributed to sites in the small loops), both functions were lost. The peptide Gly-Arg-Gly, corresponding to a repeated determinant at the tips of two small loops, inhibited translocation, but arginine alone did not. Cleavage of the large loops by CNBr also led to loss of translocation-promoting activity. The correspondence between the molecular determinants of matrix-driven translocation and those previously found for mesenchymal morphogenesis indicates the utility of this system in the analysis of adhesive interactions of biological importance.

Stuart A. Newman

Papers

The pre-Mendelian, pre-Darwinian world: shifting relations between genetic and epigenetic mechanisms in early multicellular evolution.

Phase transition and morphogenesis in a model biological system

Nuclear Localization of Type II cAMP-Dependent Protein Kinase during Limb Cartilage Differentiation Is Associated with a Novel Developmentally Regulated A-Kinase Anchoring Protein

Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. Eva Jablonka and Marion Lamb.

Interaction of fibronectin with heparin in model extracellular matrices: role of arginine residues and sulfate groups.