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

Biological Physics of the Developing Embryo: Introduction: Biology and physics

Beginning three decades ago scientists learned how to sequence DNA and transfer it from one kind of organism to another. Since that time, claims about the power of the gene to determine and transform the properties of living forms have been unremitting in academic and popular venues. When proposals were first made to improve foods and other crop plants by introducing exogenous genes (experimental transgenesis, a type of genetic engineering), unsurprisingly, questions were raised about the capability of the methods to also induce harmful effects. Scenarios included the impairment of the quality and safety of fruits and vegetables, making them allergenic or toxic to humans and nonhumans who consume them, and the creation of superweeds, which could disrupt wild or farmed ecosystems. By 2005, however, when more than 90 percent of the annual soybean crop and 50 percent of the corn crop in the United States had come to be genetically engineered*a transformation in agricultural production that took less than a decade*efforts at regulation that had once made precautionary sense were increasingly portrayed as irrational. A constant stream of articles and books by ideological technophiles and recipients of corporate largesse now portray resistance to, and even reservations

Genetically Modified Foods and the Attack on Nature

In the previous chapters we have followed the process of rapid cell divisions in the early embryo until the formation of the blastula, initially a solid mass of cells poised to develop into the structurally and functionally differentiated organism. Adhesive differentials along the surfaces of individual cells of the early blastula, the blastomeres, drive the formation of spaces or lumens (see Fig. 4.2) within the embryos of most species. As a result, the typical blastula acquires a geometrically simple closed spheroidal structure that consists of a single cell layer enclosing the hollow blastocoel. By the time the blastula has developed, the embryo already contains, or begins to generate, a number of differentiated cell types (see Chapter 3). Insofar as these cell types have or acquire distinct physical (adhesive, contractile) properties, compartmentalization or other forms of regional segregation start taking place. This regionalization, accompanied by the collective movement of the resulting cell masses, gives rise in most cases to embryos consisting of two major cell layers, referred to as “germ layers,” along with some subsidiary populations of cells. The various modes of cell rearrangement by which a solid or single-layered blastula becomes multilayered are known collectively as gastrulation . In “diploblastic” animals, such as sponges and coelenterates (hydra, jellyfish), gastrulation is complete when the two germ layers, the outer ectoderm , and inner endoderm , are established. Further cell specialization occurs within these two main layers and any subsidiary cell populations.

Biological Physics of the Developing Embryo: Epithelial morphogenesis: gastrulation and neurulation

Marta Linde-Medina’s historical and analytical essay on theories of organic form shows that the road to our contemporary understanding was bumpy and tortuous, with not everybody arriving at the same place (Linde-Medina 2010). Among modern biologists, some (the inheritors of the mid-twentieth century Modern Synthesis) advocate a view in which the forms of multicellular organisms are generated by hierarchical algorithms, inscribed in the language of nucleotide sequence. These developmental programs are presumed to have emerged through a process of relatively blind search in which individuals whose genomes contained coding changes that led to small, functionally superior anatomies and physiologies were successively enriched in their respective populations. The molding of the forms by functional requirements leads Linde-Medina to term this school of thought “externalist.” Other biologists (physicalists) hold that organisms and their organs assume stereotypic morphological motifs by virtue of the material properties of their tissues. The molding forces in this case are largely those of middle-scale (mesoscopic) self-organizing physical processes inherent to these materials, leading the author to term this view “internalist.” It is sometimes claimed that the physicalist framework denies a role for natural selection. But it can be seen from the description above that this paradigm is directed toward explaining the origination of biological forms, not their survival, persistence or abundance. Not every form that is possibly generated by self-organizing processes can find a place in the ecosystems available to it (Batten, et al. 2008). Competition for resources and mates, niche selection and construction, and many other aspects of organism-environment and organism-organism interaction classically considered by the post-Darwin synthesis must therefore enter into the scientific understanding of why the biosphere has the composition it does, even for advocates of the physicalist approach. Of course, nothing in Linde-Medina’s essay denies this.

http://www.ludus-vitalis.org/ojs/index.php/ludus/article/download/172/170

The developmental specificity of physical mechanisms

An abundant nonhistone protein (Mr, 125,000) is lost from the chromatin embryonic chicken precartilage mesenchyme cells as they differentiate into cartilage [Newman, SA., Birnbaum, J & Yeoh, G.C.T.(1976) Nature (London) 259, 417-418]. We have now examined the chromatin proteins of precartilage and cartilage cells of chicken embryos carrying the talpid2 gene which causes a perturbed patern of cartilage differentiation in the homozygous state. We find that homozygous talpid2 precartilage chromatin differs from that of the normal cell type in having its abundant precartilage chromatin protein decreased to a Mr of approximately 120,000 and in having a "precocious" cartilage-like pattern of proteins in the Mr 35,500-36,500 region. The precartilage chromatin of talpid2 heterozygotes is completely normal within the resolution of our techniques, as is the cartilage chromatin of the homozygote and heterozygote talpid2 embryos. The correlation of an aberration in a developmentally significant chromatin protein with the perturbed development of its tissue of origin is discussed.

Stuart A. Newman

Papers

Biological Physics of the Developing Embryo: Introduction: Biology and physics

Genetically Modified Foods and the Attack on Nature

Biological Physics of the Developing Embryo: Epithelial morphogenesis: gastrulation and neurulation

The developmental specificity of physical mechanisms

Talpid2 mutant of the chicken with perturbed cartilage development has an altered precartilage-specific chromatin protein