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

Ernest Everett Just's experimental work on post-fertilization events in invertebrate eggs led him to posit a dynamic and directive role for the zygotic “ectoplasm” (cortical cytoplasm), in subsequent development. His perspective was neglected during the years that followed his early death not only because of his well-documented marginalization as an African-American in U.S. science, but because his ideas were at odds with the growing gene-centrism of developmental biology in the latter half of the 20th century. This essay reviews experimental work that shows that the egg cortex in many animal groups is a chemically and mechanically active medium that sustains both spatiotemporal calcium ion transients and periodic deformations in the time leading up to cleavage. These wave phenomena are seen to play regulatory roles in germ plasm localization and gene expression, and influence the reliability and success of developmental outcomes. Just resisted vitalistic explanations for the active processes he observed and inferred regarding the egg cortical cytoplasm, but recognized that the physics and chemistry of his time were inadequate to account for these phenomena and anticipated that expansions of these fields would be necessary to explain them. Here again he proved prescient. Late 20th century developments in the physics of “excitable media” and “soft matter” have provided the bases for models, some of which are described here, of chemical and mechanochemical wave propagation in the activated egg cortex. Lastly, the implications of these post-fertilization phenomena for animal evolution, a problem also addressed by Just, are discussed. Mol. Reprod. Dev. 76: 966–974, 2009. © 2009 Wiley-Liss, Inc.

E.E. Just's "independent irritability" revisited: the activated egg as excitable soft matter.

In the 20th century, genetic explanatory approaches became dominant in both developmental and evolutionary biological research. By contrast, physical approaches, which appeal to properties such as mechanical forces, were largely relegated to the margins, despite important advances in modeling. Recently, there have been renewed attempts to find balanced viewpoints that integrate both biological physics and molecular genetics into explanations of developmental and evolutionary phenomena. Here we introduce the 2017 SICB symposium "Physical and Genetic Mechanisms for Evolutionary Novelty" that was dedicated to exploring empirical cases where both biological physics and developmental genetic considerations are crucial. To further contextualize these case studies, we offer two theoretical frameworks for integrating genetic and physical explanations: combining complementary perspectives and comprehensive unification. We conclude by arguing that intentional reflection on conceptual questions about investigation, explanation, and integration is critical to achieving significant empirical and theoretical advances in our understanding of how novel forms originate across the tree of life.

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Perspectives on Integrating Genetic and Physical Explanations of Evolution and Development: An Introduction to the Symposium.

Biological Physics of the Developing Embryo: Cleavage and blastula formation

Since the early 19 century, scientists have proposed a variety of naturalistic explanations for the organization of matter in living systems, particularly its origin and propagation from parent to offspring. Some biologists (selectionists; adaptationists) favor the idea that such organization arises by natural selection exerted on living materials with little intrinsic structure of their own. Others (structuralists; physicalists) say the complex materials that living creatures are made of have inherent self-organizational properties that determine what the life forms are and how they develop. The lack of conclusive answers despite decades of research and tens of thousands of published studies has allowed empirically unfounded creationist beliefs to persist in broad sectors of the population (Newman 2008). The still primitive understanding of the material basis of living systems also continues to instill awe in scientists, most of whom probably consider the notion of rationally designing organisms an impractical dream. However, the new field of synthetic biology now aims to change this. As I describe below, with its modus operandi of sidestepping biological origins and complexity in favor of simplification and application, ironically*and despite the intentions of the majority of scientists involved*the synthetic biology enterprise verges uncomfortably close to the metaphysics of creationism.

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Stuart A. Newman

Papers

E.E. Just's "independent irritability" revisited: the activated egg as excitable soft matter.

Perspectives on Integrating Genetic and Physical Explanations of Evolution and Development: An Introduction to the Symposium.

Biological Physics of the Developing Embryo: Cleavage and blastula formation

Synthetic Biology: Life as App Store

Biological Physics of the Developing Embryo: Organogenesis