Homeostasis as the Mechanism of Evolution.

Homeostasis is conventionally thought of merely as a synchronic (same time) servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time) mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology

Pleiotropy as the Mechanism for Evolving Novelty: Same Signal, Different Result.

In contrast to the probabilistic way of thinking about pleiotropy as the random expression of a single gene that generates two or more distinct phenotypic traits, it is actually a deterministic consequence of the evolution of complex physiology from the unicellular state. Pleiotropic novelties emerge through recombinations and permutations of cell-cell signaling exercised during reproduction based on both past and present physical and physiologic conditions, in service to the future needs of the organism for its continued survival. Functional homologies ranging from the lung to the kidney, skin, brain, thyroid and pituitary exemplify the evolutionary mechanistic strategy of pleiotropy. The power of this perspective is exemplified by the resolution of evolutionary gradualism and punctuated equilibrium in much the same way that Niels Bohr resolved the paradoxical duality of light as Complementarity

A systematic approach to cancer: evolution beyond selection.

Cancer is typically scrutinized as a pathological process characterized by chromosomal aberrations and clonal expansion subject to stochastic Darwinian selection within adaptive cellular ecosystems. Cognition based evolution is suggested as an alternative approach to cancer development and progression in which neoplastic cells of differing karyotypes and cellular lineages are assessed as self-referential agencies with purposive participation within tissue microenvironments. As distinct self-aware entities, neoplastic cells occupy unique participant/observer status within tissue ecologies. In consequence, neoplastic proliferation by clonal lineages is enhanced by the advantaged utilization of ecological resources through flexible re-connection with progenitor evolutionary stages

The Unicellular State as a Point Source in a Quantum Biological System.

A point source is the central and most important point or place for any group of cohering phenomena. Evolutionary development presumes that biological processes are sequentially linked, but neither directed from, nor centralized within, any specific biologic structure or stage. However, such an epigenomic entity exists and its transforming effects can be understood through the obligatory recapitulation of all eukaryotic lifeforms through a zygotic unicellular phase. This requisite biological conjunction can now be properly assessed as the focal point of reconciliation between biology and quantum phenomena, illustrated by deconvoluting complex physiologic traits back to their unicellular origins

Cell-cell communication predicts aging, senescence and death: an integrated, predictive evolutionary approach

None of the extant theories of aging have proven to be effective in advancing our knowledge of senescence or mortality. In contrast to the gene-centric focus on evolution, the mechanism of cell-cell interactions as the driving force for evolution as the logic of biology is proposed. Since the distribution of  bioenergy over the course of the life cycle is skewed towards the reproductive phase, bioenergy flags in the post-reproductive stage of life, causing failure of cell-cell signaling, loss of homeostatic control, senescence and death. In the interim, the phenotype acts as the ‘agent’ for epigenetic inheritance, obtaining ‘marks’ that inform the organism of changes in the environment. Such marks are inherited by the offspring, providing it with foreknowledge of the environment to come. The organism appears to ‘return’ to the unicellular state over the course of the life cycle, but in reality meiosis is the mechanism of epigenetic inheritance, the adult phenotype being the means for transmitting the epigenetic marks obtained from the environment back to the organism

Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cell–cell signaling and extrinsic factors is the reverse of the “top-down” conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a “middle-out” cell–cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cell–cell communication as the basis for complex physiologic traits, from sponges to man

Evolution, the ‘Mechanism’ of Big History: The Grande Synthesis

Big History traces the Cosmologic arc from the Singularity/Big Bang to the present. Similarly, evolutionary biology, as “all of biology”, represents the arc of life from its origins. There is mechanistic consilience between Quantum Mechanics, The First Principles of PhYsiology and evolutionary biology that is perpetually centered on the unicellular level. The phenotypic adaptations in reaction to geophysical and geochemical changes that culminate in culture are forged at the level of the recapitulating unicellular zygote. This perspective offers a synthesis for the animate and inanimate alike as Big History. The cell as the mechanistic basis for both evolution and Big History offers a novel synthesis for Humanism and Science

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats.

BackgroundBy stimulating lipofibroblast maturation, parenterally administered peroxisome proliferator-activated receptor γ (PPARγ) agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury.MethodsOne-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24 h; animals were exposed to 21% or 95% O2 for up to 72 h. Twenty-four and 72 h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels.ResultsNebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.ConclusionNebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females