Comprehensive Physiology Wiley Online Library

Unitary Physiology

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ABSTRACT

The common relationships among a great variety of biological phenomena seem enigmatic when considered solely at the level of the phenotype. The deep connections in physiology, for example, between the effects of maternal food restriction in utero and the subsequent incidence of metabolic syndrome in offspring, the effects of microgravity on cell polarity and reproduction in yeast, stress effects on jellyfish, and their endless longevity, or the relationship between nutrient abundance and the colonial form in slime molds, are not apparent by phenotypic observation. Yet all of these phenomena are ultimately determined by the Target of Rapamycin (TOR) gene and its associated signaling complexes. In the same manner, the unfolding of evolutionary physiology can be explained by a comparable application of the common principle of cell‐cell signaling extending across complex developmental and phylogenetic traits. It is asserted that a critical set of physiologic and phenotypic adaptations emanated from a few crucial, ancestral receptor gene duplications that enabled the successful terrestrial transition of vertebrates from water to land. In combination, mTor and its cognate receptors and a few crucial genetic duplications provide a mechanistic common denominator across a diverse spectrum of biological responses. The proper understanding of their purpose yields a unified concept of physiology and its evolutionary development. © 2018 American Physiological Society. Compr Physiol 8:761‐771, 2018.

References
 1.Aberg KM, Man MQ, Gallo RL, Ganz T, Crumrine D, Brown BE, Choi EH, Kim DK, Schröder JM, Feingold KR, Elias PM. Co‐regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. J Invest Dermatol 128: 917‐925, 2008.
 2.Aris‐Brosou S, Chen X, Perry SF, Moon TW. Timing of the functional diversification of alpha‐ and beta‐adrenoceptors in fish and other vertebrates. Ann N Y Acad Sci 1163: 343‐347, 2009.
 3.Ballweg S, Ernst R. Control of membrane fluidity: The OLE pathway in focus. Biol Chem 398: 215‐228, 2017.
 4.Barker DJ. The developmental origins of adult disease. J Am Coll Nutr 23: 588S‐595S, 2004.
 5.Barker DJ. The origins of the developmental origins theory. J Intern Med 261: 412‐417, 2007.
 6.Beall MH, van den Wijngaard JP, van Gemert MJ, Ross MG. Amniotic fluid water dynamics. Placenta 28: 816‐823, 2007.
 7.Bernhard W. Lung surfactant: Function and composition in the context of development and respiratory physiology. Ann Anat 208: 146‐150, 2016.
 8.Besnard V, Wert SE, Stahlman MT, Postle AD, Xu Y, Ikegami M, Whitsett JA. Deletion of Scap in alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts. J Biol Chem 284: 4018‐4030, 2009.
 9.Bloch K. Sterol molecule: Structure, biosynthesis, and function. Steroids 57: 378‐383, 1992.
 10.Bosch RJ, Rodríguez‐Puyol D, Bover J, Rodríguez‐Puyol M. Parathyroid hormone‐related protein: Roles in the glomerulus. Exp Nephrol 7: 212‐216, 1999.
 11.Bosch RJ, Rojo‐Linares P, Torrecillas‐Casamayor G, Iglesias‐Cruz MC, Rodríguez‐Puyol D, Rodríguez‐Puyol M. Effects of parathyroid hormone‐related protein on human mesangial cells in culture. Am J Physiol 277: E990‐E995, 1999.
 12.Boyce WT, Kobor MS. Development and the epigenome: The ‘synapse’ of gene‐environment interplay. Dev Sci 18: 1‐23, 2015.
 13.Bridgham JT, Carroll SM, Thornton JW. Evolution of hormone‐receptor complexity by molecular exploitation. Science 312: 97‐101, 2006.
 14.Brown JM, Firtel RA. Regulation of cell‐fate determination in Dictyostelium. Dev Biol 216: 426‐441, 1999.
 15.Canales J. The Physicist and the Philosopher. Princeton, NJ: Princeton University Press, 2015.
 16.Cannon WB. The Wisdom of the Body. New York: W.W. Norton, 1963.
 17.Cappellesso R, Nicole L, Guido A, Pizzol D. Spaceflight osteoporosis: Current state and future perspective. Endocr Regul 49: 231‐239, 2015.
 18.Case RM, Eisner D, Gurney A, Jones O, Muallem S, Verkhratsky A. Evolution of calcium homeostasis: From birth of the first cell to an omnipresent signaling system. Cell Calcium 42: 345‐350, 2007.
 19.Clack JA. Gaining Ground. Bloomington, IN: Indiana University Press, 2012.
 20.Cohen KM, Finney SC, Gibbard, PL, Fan, J‐X. Episodes 36: 199‐204. International Commission on Stratigraphy 2013.
 21.Collins S, Bolanowski MA, Caron MG, Lefkowitz RJ. Genetic regulation of beta‐adrenergic receptors. Annu Rev Physiol 51: 203‐215, 1989.
 22.Crick F. Central dogma of molecular biology. Nature 1970, 227: 561‐563.
 23.Daniels CB, Orgeig S. The comparative biology of pulmonary surfactant: Past, present and future. Comp Biochem Physiol A Mol Integr Physiol 129: 9‐36, 2001.
 24.Daniels CB, Orgeig S, Sullivan LC, Ling N, Bennett MB, Schürch S, Val AL, Brauner CJ. The origin and evolution of the surfactant system in fish: Insights into the evolution of lungs and swim bladders. Physiol Biochem Zool 77: 732‐749, 2004.
 25.Dasgupta C, Sakurai R, Wang Y, Guo P, Ambalavanan N, Torday JS, Rehan VK. Hyperoxia‐induced neonatal rat lung injury involves activation of TGF‐{beta} and Wnt signaling and is protected by rosiglitazone. Am J Physiol Lung Cell Mol Physiol 296: L1031‐L1041, 2009.
 26.De Duve C. Evolution of the peroxisome. Ann N Y Acad Sci 168: 369‐381, 1969.
 27.Deamer D. The role of lipid membranes in life's origin. Life (Basel) 7(1): 5, 2017.
 28.Demayo F, Minoo P, Plopper CG, Schuger L, Shannon J, Torday JS. Mesenchymal‐epithelial interactions in lung development and repair: Are modeling and remodeling the same process? Am J Physiol Lung Cell Mol Physiol 4283: L510‐L517, 2002.
 29.Deng YL, Xiong XZ, Cheng NS. Organ fibrosis inhibited by blocking transforming growth factor‐β signaling via peroxisome proliferator‐activated receptor γ agonists. Hepatobiliary Pancreat Dis Int 11: 467‐478, 2012.
 30.Dollo, L. Les lois de l'évolution. Bull Soc Belge Geol Pal Hydr VII: 164–166, 1893.
 31.Edeling M, Ragi G, Huang S, Pavenstädt H, Susztak K. Developmental signaling pathways in renal fibrosis: The roles of Notch, Wnt and Hedgehog. Nat Rev Nephrol 12: 426‐439, 2016.
 32.Escolar JD, Escolar A. Lung hysteresis: A morphological view. Histol Histopathol 19: 159–166, 2004.
 33.Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, Vazquez J, Valencia A, Tress ML. Multiple evidence strands suggest that there may be as few as 19,000 human protein‐coding genes. Hum Mol Genet 23: 5866‐5878, 2014.
 34.Fajardo G, Zhao M, Urashima T, Farahani S, Hu DQ, Reddy S, Bernstein D. Deletion of the β2‐adrenergic receptor prevents the development of cardiomyopathy in mice. J Mol Cell Cardiol 63: 155‐164, 2013.
 35.Fang Y, Tan J, Zhang Q. Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells. Cell Biol Int 39: 891‐898, 2015.
 36.Fiaturi N, Castellot JJ Jr, Nielsen HC. Neuregulin‐ErbB4 signaling in the developing lung alveolus: A brief review. J Cell Commun Signal 8: 105‐111, 2014.
 37.Foley J, Longely BJ, Wysolmerski JJ, Dreyer BE, Broadus AE, Philbrick WM. PTHrP regulates epidermal differentiation in adult mice. J Invest Dermatol 111: 1122‐1128, 1998.
 38.Fung E, Tsukamoto H. Morphogen‐related therapeutic targets for liver fibrosis. Clin Res Hepatol Gastroenterol 39: S69‐S74, 2015.
 39.Gao Y, Raj JU. Parathyroid hormone‐related protein‐mediated responses in pulmonary arteries and veins of newborn lambs. Am J Physiol Lung Cell Mol Physiol 289: L60‐L66, 2005.
 40.Gould SJ, Vrba ES. Exaptation—a missing term in the science of form. Paleobiology 8: 4‐15, 1982.
 41.Griffiths WJ, Abdel‐Khalik J, Yutuc E, Morgan AH, Gilmore I, Hearn T, Wang Y. Cholesterolomics: An update. Anal Biochem 524: 56‐67, 2017.
 42.Gu Z, Liu Y, Zhang Y, Jin S, Chen Q, Goltzman D, Karaplis A, Miao D. Absence of PTHrP nuclear localization and carboxyl terminus sequences leads to abnormal brain development and function. PLoS One 7: e41542, 2012.
 43.Guex J. Retrograde Evolution During Major Extinction Crises. New York: Springer, 2016.
 44.Hallman M, Glumoff V, Rämet M. Surfactant in respiratory distress syndrome and lung injury. Comp Biochem Physiol A Mol Integr Physiol 129: 287‐294, 2001.
 45.Himms‐Hagen J. Lipid metabolism during cold‐exposure and during cold‐acclimation. Lipids 7: 310‐323, 1972.
 46.Hobson JA, Hong CC, Friston KJ. Virtual reality and consciousness inference in dreaming. Front Psychol 5: 1133, 2014.
 47.Hochane M, Raison D, Coquard C, Imhoff O, Massfelder T, Moulin B, Helwig JJ, Barthelmebs M. Parathyroid hormone‐related protein is a mitogenic and a survival factor of mesangial cells from male mice: Role of intracrine and paracrine pathways. Endocrinology 154: 853‐864, 2013.
 48.Howden R, Kleeberger SR. Genetic and environmental influences on gas exchange. Compr Physiol 2: 2595‐2614, 2012.
 49.Hsia CC, Hyde DM, Weibel ER. Lung structure and the intrinsic challenges of gas exchange. Compr Physiol 6: 827‐895, 2016.
 50.Hu Y, Lu Q, Liu W, Zhang Y, Li M, Zhao H. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction. PLoS Genet 13: e1006836, 2017.
 51.Huang K, Fingar DC. Growing knowledge of the mTOR signaling network. Semin Cell Dev Biol 36: 79‐90, 2014.
 52.Janský L. Humoral control of hyper‐ and hypometabolic states. J Physiol (Paris) 78: 872‐874, 1982‐1983.
 53.Jia G, Aroor AR, Martinez‐Lemus LA, Sowers JR. Overnutrition, mTOR signaling, and cardiovascular diseases. Am J Physiol Regul Integr Comp Physiol 307: R1198‐R1206, 2014.
 54.Kakui Y, Sato M. Differentiating the roles of microtubule‐associated proteins at meiotic kinetochores during chromosome segregation. Chromosoma 125: 309‐320, 2016.
 55.Kaller M, Nellen W, Chubb JR. Epigenetics in Dictyostelium. Methods Mol Biol 346: 491‐505, 2006.
 56.Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VL, Kronenberg HM, Mulligan RC. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone‐related peptide gene. Genes Dev 8: 277‐289, 1994.
 57.Kasahara Y, Takayanagi Y, Kawada T, Itoi K, Nishimori K. Impaired thermoregulatory ability of oxytocin‐deficient mice during cold‐exposure. Biosci Biotechnol Biochem 71: 3122‐3126 2007.
 58.Korzh S, Winata CL, Zheng W, Yang S, Yin A, Ingham P, Korzh V, Gong Z. The interaction of epithelial Ihha and mesenchymal Fgf10 in zebrafish esophageal and swimbladder development. Dev Biol 359: 262‐276, 2011.
 59.Koupil I. The Uppsala studies on developmental origins of health and disease. J Intern Med 261: 426‐436, 2007.
 60.Krebs HA. The August Krogh Principle: “For many problems there is an animal on which it can be most conveniently studied.” J Exp Zool 194: 221‐226, 1975.
 61.Lang F, Pearce D. Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway. Nephrol Dial Transplant 31: 200‐205, 2016.
 62.Lehmann M, Baarsma HA, Königshoff M. WNT signaling in lung aging and disease. Ann Am Thorac Soc 13: S411‐S416, 2016.
 63.Lelièvre SA. Tissue polarity‐dependent control of mammary epithelial homeostasis and cancer development: An epigenetic perspective. J Mammary Gland Biol Neoplasia 15: 49‐63, 2010.
 64.Leszczyńska‐Gorzelak B. Fetal programming of the metabolic syndrome. Taiwan J Li, J. Molecular regulators of nerve conduction—lessons from inherited neuropathies and rodent genetic models. Exp Neurol 267: 209‐218, 2015.
 65.Li J. Molecular regulators of nerve conduction—lessons from inherited neuropathies and rodent genetic models. Exp Neurol 267: 209‐218, 2015.
 66.Lindsey BW, Smith FM, Croll RP. From inflation to flotation: contribution of the swimbladder to whole‐body density and swimming depth during development of the zebrafish (Danio rerio). Zebrafish 7: 85‐96, 2010.
 67.Lingwood D, Simons K. Lipid rafts as a membrane‐organizing principle. Science 327: 46‐50, 2010.
 68.Lisenkova AA, Grigorenko AP, Tyazhelova TV, Andreeva TV, Gusev FE, Manakhov AD, Goltsov AY, Piraino S, Miglietta MP, Rogaev EI. Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii, the “immortal” jellyfish with a reversible life‐cycle. Mol Phylogenet Evol 107: 232‐238, 2017.
 69.Longo S, Bollani L, Decembrino L, Di Comite A, Angelini M, Stronati M. Short‐term and long‐term sequelae in intrauterine growth retardation (IUGR). J Matern Fetal Neonatal Med 26: 222‐225, 2013.
 70.Machamer P, Darden L, Carver CF. Thinking about mechanisms. Phil Sci 67: 1‐25, 2000.
 71.Maina JN. Structure, function and evolution of the gas exchangers: Comparative perspectives. J Anat 201: 281‐304, 2002.
 72.Maina JN. Critical appraisal of some factors pertinent to the functional designs of the gas exchangers. Cell Tissue Res 367: 747‐767, 2017.
 73.Marciniak A, Patro‐Małysza J, Kimber‐Trojnar Ż, Marciniak B, Oleszczuk J, Leszczyńska‐Gorzelak B. Fetal programming of the metabolic syndrome. Taiwan J Obstet Gynecol 56: 133‐138, 2017
 74.Margulis, L. Symbiogenesis. A new principle of evolution rediscovery of Boris Mikhaylovich Kozo‐Polyansky (1890–1957). Paleontol J 44: 1525–1539, 2011.
 75.McEwen BS, Wingfield JC. The concept of allostasis in biology and biomedicine. Mechanotransduction in lung development. Am J Med Sci 316: 205‐208, 1998.
 76.Miller WB. Cognition, information fields and hologenomic entanglement: Evolution in light and shadow. Biology (Basel) 5(2): 21, 2016.
 77.Miller WB Jr, Torday JS. A systematic approach to cancer: Evolution beyond selection. Clin Transl Med 6: 2, 2017.
 78.Milsom WK, Jackson DC. Hibernation and gas exchange. Compr Physiol 1: 397‐420, 2011.
 79.Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi‐osmotic type of mechanism. Nature 191: 144‐148, 1961.
 80.Moss L. Is the philosophy of mechanism philosophy enough? Stud Hist Philos Biol Biomed Sci 43: 164‐172, 2012.
 81.Mouritsen OG, Zuckermann MJ. What's so special about cholesterol? Lipids 39(11): 1101‐1113, 2004.
 82.Najrana T, Sanchez‐Esteban J. Mechanotransduction as an adaptation to gravity. Front Pediatr 4: 140, 2016.
 83.Neary R, Watson CJ, Baugh JA. Epigenetics and the overhealing wound: The role of DNA methylation in fibrosis. Fibrogenesis Tissue Repair 8: 18, 2015.
 84.Nicholson DJ. The concept of mechanism in biology. Stud Hist Philos Biol Biomed Sci 43: 152‐163, 2012.
 85.Ohashi K, Fujiwara S, Mizuno K. Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction. J Biochem 161: 245‐254, 2017.
 86.Orgeig S, Daniels CB. The roles of cholesterol in pulmonary surfactant: Insights from comparative and evolutionary studies. Comp Biochem Physiol A Mol Integr Physiol 129: 75‐89, 2001.
 87.Orgeig S, Morrison JL, Daniels CB. Evolution, development, and function of the pulmonary surfactant system in normal and perturbed environments. Compr Physiol 6: 363‐422, 2015.
 88.Painter, RC; Osmond, C; Gluckman, P; Hanson, M; Phillips, DI; Roseboom, TJ. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG 115: 1243‐1249, 2008.
 89.Parker, LN. Adrenarche. Endocrinol Metab Clin North Am 20: 71‐83, 1991.
 90.Perry SF, Sander M. Reconstructing the evolution of the respiratory apparatus in tetrapods. Respir Physiol Neurobiol 144: 125‐139, 2004.
 91.Perry SF, Carrier DR. The coupled evolution of breathing and locomotion as a game of leapfrog. Physiol Biochem Zool 79: 997‐999, 2006.
 92.Pinheiro PL, Cardoso JC, Power DM, Canário AV. Functional characterization and evolution of PTH/PTHrP receptors: Insights from the chicken. BMC Evol Biol 12: 110, 2012.
 93.Pires‐daSilva A, Sommer RJ. The evolution of signalling pathways in animal development. Nat Rev Genet 4: 39‐49, 2003.
 94.Plato: Timaeus, Critias, Cleitophon, Menexenus, Epistles. Cambridge, UK: Harvard University Press, 1929.
 95.Prem C, Salvenmoser W, Würtz J, Pelster B. Swim bladder gas gland cells produce surfactant: in vivo and in culture. Am J Physiol Regul Integr Comp Physiol 279: R2336‐R2343, 2000.
 96.Purevdorj‐Gage B, Sheehan KB, Hyman LE. Effects of low‐shear modeled microgravity on cell function, gene expression, and phenotype in Saccharomyces cerevisiae. Appl Environ Microbiol 72: 4569‐4575, 2006.
 97.Rehan VK, Fong J, Lee R, Sakurai R, Wang ZM, Dahl MJ, Lane RH, Albertine KH, Torday JS. Mechanism of reduced lung injury by high‐frequency nasal ventilation in a preterm lamb model of neonatal chronic lung disease. Pediatr Res 70: 462‐466, 2011.
 98.Rehan VK, Li Y, Corral J, Saraswat A, Husain S, Dhar A, Sakurai R, Khorram O, Torday JS. Metyrapone blocks maternal food restriction‐induced changes in female rat offspring lung development. Reprod Sci 21: 517‐525, 2014.
 99.Rehan VK, Torday JS. Exploiting the PTHrP signaling pathway to treat chronic lung disease. Drugs Today (Barc) 43: 317‐331, 2007.
 100.Rehan VK, Torday JS. PPARγ signaling mediates the evolution, development, homeostasis, and repair of the lung. PPAR Res 2012: 289867, 2012.
 101.Rehan VK, Wang Y, Sugano S, Romero S, Chen X, Santos J, Khazanchi A, Torday JS. Mechanism of nicotine‐induced pulmonary fibroblast transdifferentiation. Am J Physiol Lung Cell Mol Physiol 289: L667‐L6676, 2005.
 102.Romer AS. The Vertebrate Story. Chicago, IL: University of Chicago Press, Chicago, 1949.
 103.Rubin LP, Kovacs CS, De Paepe ME, Tsai SW, Torday JS, Kronenberg HM. Arrested pulmonary alveolar cytodifferentiation and defective surfactant synthesis in mice missing the gene for parathyroid hormone‐related protein. Dev Dyn 230: 278‐289, 2004.
 104.Ruiz‐Camp J, Morty RE. Divergent fibroblast growth factor signaling pathways in lung fibroblast subsets: Where do we go from here? Am J Physiol Lung Cell Mol Physiol 309: L751‐L755, 2015.
 105.Sanchez‐Esteban J, Tsai SW, Sang J, Qin J, Torday JS, Rubin LP. Effects of mechanical forces on lung‐specific gene expression. Am J Med Sci 316: 200‐204, 1998.
 106.Santrock JW. Children. 9. New York, NY: McGraw‐Hill, 1998.
 107.Najrana RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 168: 960‐976, 2017.
 108.Schrodinger E. What is Life? New York, NY: MacMillan, 1944.
 109.Schulz LC. The Dutch Hunger Winter and the developmental origins of health and disease. Proc Natl Acad Sci U S A 107: 16757‐16758, 2010.
 110.Schutz B. Gravity from the Ground Up: An Introductory Guide to Gravity and General Relativity. Cambridge, UK: Cambridge University Press, 2004.
 111.Seki Y, Williams L, Vuguin PM, Charron MJ. Minireview: Epigenetic programming of diabetes and obesity: Animal models. Endocrinology 153: 1031‐1038, 2012.
 112.Shapiro JA. Evolution, A View from the 21st Century. Indianapolis, IN: FT Press Science, 2011.
 113.Soliman GA. The mammalian target of rapamycin signaling network and gene regulation. Curr Opin Lipidol 16: 317‐323, 2005.
 114.Storr SJ, Woolston CM, Zhang Y, Martin SG. Redox environment, free radical, and oxidative DNA damage. Antioxid Redox Signal 18: 2399‐23408, 2013.
 115.Suri LN, McCaig L, Picardi MV, Ospina OL, Veldhuizen RA, Staples JF, Possmayer F, Yao LJ, Perez‐Gil J, Orgeig S. Adaptation to low body temperature influences pulmonary surfactant composition thereby increasing fluidity while maintaining appropriately ordered membrane structure and surface activity. Biochim Biophys Acta 1818: 1581‐1589, 2012.
 116.Swanson AM, David AL. Animal models of fetal growth restriction: Considerations for translational medicine. Placenta 36: 623‐630, 2015.
 117.Symonds ME, Sebert SP, Hyatt MA, Budge H. Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol. 5: 604‐610, 2009.
 118.Tadenev ALD, Tarchini B. The spindle orientation machinery beyond mitosis: When cell specialization demands polarization. Adv Exp Med Biol 1002: 209‐225, 2017.
 119.Torday JS. Parathyroid hormone‐related protein is a gravisensor in lung and bone cell biology. Adv Space Res 32: 1569‐1576, 2003.
 120.Torday JS. Evolution and cell physiology. 1. Cell signaling is all of biology. Am J Physiol Cell Physiol 305: C682‐C689, 2013.
 121.Torday JS. Evolutionary biology redux. Perspect Biol Med 56: 455‐484, 2013.
 122.Torday JS. A central theory of biology. Med Hypotheses 85: 49‐57, 2015.
 123.Torday JS. Homeostasis as the mechanism of evolution. Biology (Basel) 4: 573‐590, 2015.
 124.Torday JS. Life is simple‐biologic complexity is an epiphenomenon. Biology (Basel) 5(2): 17, 2016.
 125.Torday JS. Heterochrony as diachronically modified cell‐cell interactions. Biology (Basel) 5(1): 4, 2016.
 126.Torday J, Rehan V. Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression. Exp Lung Res 37: 376‐386, 2011.
 127.Torday JS, Miller WB. The unicellular state as a point source in a quantum biological system. Biology (Basel) 5(2): 2016.
 128.Torday JS, Miller WB. Phenotype as agent for epigenetic inheritance. Biology (Basel) 5(3), 2016.
 129.Torday JS, Miller WB Jr. Biologic relativity: Who is the observer and what is observed? Prog Biophys Mol Biol 121: 29‐34, 2016.
 130.Torday JS, Miller WB Jr. On the evolution of the mammalian brain. Front Syst Neurosci 10: 31, 2016.
 131.Torday JS, Miller WB Jr. A systems approach to physiologic evolution: From micelles to consciousness. J Cell Physiol 233: 162‐167, 2017.
 132.Torday JS, Rehan VK. Stretch‐stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin. Am J Physiol Lung Cell Mol Physiol 283: L130‐L135, 2002.
 133.Torday JS, Rehan VK. Mechanotransduction determines the structure and function of lung and bone: A theoretical model for the pathophysiology of chronic disease. Cell Biochem Biophys 37: 235‐246, 2003.
 134.Torday JS, Rehan VK. Deconvoluting lung evolution using functional/comparative genomics. Am J Respir Cell Mol Biol 31: 8‐12, 2004.
 135.Torday JS, Rehan VK. The evolutionary continuum from lung development to homeostasis and repair. Am J Physiol Lung Cell Mol Physiol 292: L608‐L611, 2007.
 136.Torday JS, Rehan VK. Cell‐cell signaling drives the evolution of complex traits: Introduction‐lung evo‐devo. Integr Comp Biol 49: 142‐154, 2009.
 137.Torday JS, Rehan VK. The evolution of cell communication: The road not taken. Cell Commun Insights 2: 17‐25, 2009.
 138.Torday JS, Rehan VK. Evolutionary Biology, Cell‐Cell Communication and Complex Disease. Hoboken, NJ: Wiley, 2012.
 139.Torday JS, Rehan VK. On the evolution of the pulmonary alveolar lipofibroblast. Exp Cell Res 340: 215‐219, 2016.
 140.Torday JS, Rehan VK. Evolution, the Logic of Biology. London, UK: Wiley‐Blackwell, 2017.
 141.Torday JS, Sanchez‐Esteban J, Rubin LP. Paracrine mediators of mechanotransduction in lung development. Am J Med Sci 316: 205‐208, 1998.
 142.Varela FG, Maturana HR, Uribe R. Autopoiesis: The organization of living systems, its characterization and a model. Curr Mod Biol 5: 187‐196, 1974.
 143.Warburton D, El‐Hashash A, Carraro G, Tiozzo C, Sala F, Rogers O, De Langhe S, Kemp PJ, Riccardi D, Torday J, Bellusci S, Shi W, Lubkin SR, Jesudason E. Lung organogenesis. Curr Top Dev Biol 90: 73‐158, 2010.
 144.Watson RA, Szathmáry E. How can evolution learn? Trends Ecol Evol 31: 147‐157, 2016.
 145.West JB. Role of the fragility of the pulmonary blood‐gas barrier in the evolution of the pulmonary circulation. Am J Physiol Regul Integr Comp Physiol 304: R171‐R176, 2013.
 146.West JB, Elliott AR, Guy HJ, Prisk GK. Pulmonary function in space. JAMA 277: 1957‐1961, 1997.
 147.Xu Y, Lai E, Liu J, Lin J, Yang C, Jia C, Li Y, Bai X, Li M. IKK interacts with rictor and regulates mTORC2. Cell Signal 25: 2239‐2245, 2013.
 148.Yao NY, Potter AC, Potirniche I‐D, Vishwanath A. Discrete time crystals: Rigidity, criticality, and realizations. Phys Rev Lett 118(3), 2017.
 149.Zheng W, Wang Z, Collins JE, Andrews RM, Stemple D, Gong Z. Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung. PLoS One 6: e24019, 2011.

Teaching Material

J. S. Torday, W. B. Miller, Jr. Unitary Physiology. Compr Physiol. 8: 2018, 761-771.

Didactic Synopsis

Major Teaching Points:

  • By using the cell-cell interaction mechanisms of embryogenesis and phylogeny, physiology can be understood as a continuous process of evolution from unicellular to multicellular organisms.
  • First principles of physiology: The origins of life as prototypical cells is predicated on negative entropy, driven by chemiosmosis, and controlled by homeostasis.
  • Growth factor signaling: Cells determine their phenotypes using soluble growth factors, both to adapt to their environment and to one another.
  • From embryogenesis to homeostasis: The culmination of morphologic development is the growth factor signaling that maintains and regenerates cell physiology of tissues, organs, and organisms.
  • Homeostasis as the mechanism for evolution: the cell signaling mechanisms that establish homeostasis are “plastic,” monitoring the environment to determine whether to remain at equipoise or change to adapt to change.
  • Evolution as iterative preadaptations/exaptations: The cellular changes that occur during evolution are derived from preexisting genetic mechanisms that are reallocated to adapt to new conditions.
  • Pleiotropy as a way of understanding physiologic complexity: The evolutionary reallocation of genetic mechanisms is manifested as pleiotropy, the same gene controlling different structures/functions.


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How to Cite

John S. Torday, William B. Miller, Jr. Unitary Physiology. Compr Physiol 2018, 8: 761-771. doi: 10.1002/cphy.c170035