I argue that Descartes explains physiology in terms of whole systems, and not in terms of the size, shape and motion of tiny corpuscles (corpuscular mechanics). It is a standard, entrenched view that Descartes’ proper means of explanation in the natural world is through strict reduction to corpuscular mechanics. This view is bolstered by a handful of corpuscular–mechanical explanations in Descartes’ physics, which have been taken to be representative of his treatment of all natural phenomena. However, Descartes’ explanations of (...) the ‘principal parts’ of physiology do not follow the corpuscular–mechanical pattern. Des Chene has identified systems in Descartes’ account of physiology, but takes them ultimately to reduce down to the corpuscle level. I argue that they do not. Rather, Descartes maintains entire systems, with components selected from multiple levels of organization, in order to construct more complete explanations than corpuscular mechanics alone would allow. (shrink)

Descartes understood the subject matter of physics (or natural philosophy) to encompass the whole of nature, including living things. It therefore comprised not only nonvital phenomena, including those we would now denominate as physical, chemical, minerological, magnetic, and atmospheric; it also extended to the world of plants and animals, including the human animal (with the exception of those aspects of the human mind that Descartes assigned to solely to thinking substance: pure intellect and will). Descartes wrote extensively on physiology (...) and on the physiology and psychology of the senses. This chapter examines the notions of *physiology* and *psychology* in medical and natural philosophical works of Descartes' day; follows his efforts to bring physiology into his mechanistic idiom; considers the relation between physiology of the animal machine and psychological functions that yield functionally appropriate behavior; goes into his physiology and psychology of vision; and elaborates the tension in Descartes' works between his metaphysically supported micro-corpuscularism and his discussion of the animal machine as an organic unity comprising various functionally and teleologically characterized systems. The chapter draws on Descartes' works in both metaphysics and natural philosophy, including his Treatise on Man (originally published as L'Homme, 1664). (shrink)

Based on genetic and biochemical advances on the molecular mechanism of circadian rhythms, a computational model for the mammalian circadian clock is used to examine the dynamical bases of circadian‐clock‐related physiological disorders in humans. Entrainment by the light–dark cycle with a phase advance or a phase delay is associated with the Familial advanced sleep phase syndrome (FASPS) or the Delayed sleep phase syndrome (DSPS), respectively. Lack of entrainment corresponding to the occurrence of quasiperiodic oscillations with or without phase jump can (...) be associated with the non‐24 h sleep–wake syndrome. In the close vicinity of the entrainment domain, the model uncovers the possibility of infradian oscillations of very long period. Perturbation in the form of chronic jet lag, as used in mice, prevents entrainment of the circadian clock and results in chaotic or quasiperiodic oscillations. It is important to clarify the conditions for entrainment and for its failure because dysfunctions of the circadian clock may lead to physiological disorders, which pertain not only to the sleep–wake cycle but also to mood and cancer. BioEssays 30:590–600, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded. An increase in cellular glucose uptake will lead to increased production (...) of ROS. This in turn activates the stress‐responsive Jun‐N‐terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance. Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state. BioEssays 29:811–818, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Chakras are a basic concept of yoga but typically are ignored by scientific research on yoga, probably because descriptions of chakras can appear like a fanciful mythology. Chakras are commonly considered to be centers of concentrated metaphysical energy. Although clear physiological effects exist for yoga practices, no explanation of how chakras influence physiological function has been broadly accepted either in the scientific community or among yoga scholars. This problem is exacerbated by the fact that yoga is based on subjective experience, (...) and practitioners often shun objective descriptions. This essay builds on earlier work hypothesizing that intercellular gap junction connections provide a physiological mechanism underlying subtle energy systems described in yoga as well as other disciplines such as acupuncture. Three physical aspects of chakras are distinguished that are integrated through gap junction mechanisms and are proposed to have arisen during embryological development. Furthermore, electrical conductance associated with a high concentration of gap junctions could generate phenomena that, when subjectively experienced, have the radiant qualities attributed to chakras. This theory provides a scientific rationale for previously unexplained details of chakra theory and offers a new orientation to conceptualizing and studying such subjective phenomena. (shrink)

Recent research has pointed to the importance of the prenatal environment in the etiology of autism spectrum disorder (ASD) but the biological mechanisms which mitigate these environmental factors are not clear. Mitochondrial metabolism abnormalities, inflammation and oxidative stress as common physiological disturbances associated with ASD. Network analysis of the scientific literature identified several leading prenatal environmental factors associated with ASD, particularly air pollution, pesticides, the microbiome and epigenetics. These leading prenatal environmental factors were found to be most associated with inflammation, (...) followed by oxidative stress and mitochondrial dysfunction. Other prenatal factors associated with ASD not identified by the network analysis were also found to be significantly associated with these common physiological disturbances. A better understanding of the biological mechanism which mediate the effect of prenatal environmental factors can lead to insights of how ASD develops and the development of targeted therapeutics to prevent ASD from occuring. (shrink)

It is commonplace for a single physiological mechanism to seed multiple phenomena, and for multiple mechanisms to contribute to a single phenomenon. We propose that the flash-lag effect should not be considered a phenomenon with a single cause. Instead, its various aspects arise from the convergence of a number of different mechanisms proposed in the literature. We further give an example of how a neuron's generic spatio-temporal response profile can form a physiological basis not only of but also of many (...) of the other proposed flash-lag mechanisms, thus recapitulating a spectrum of flash-lag phenomena. Finally, in agreeing that such basic predictive mechanisms are present throughout the brain, we argue that motor prediction contributes more to biological fitness than visual prediction. (shrink)

Nielsen has not demonstrated that NREM dreams are regularly accompanied by fragments of the REM state. However, even if this hypothetical correlation could be demonstrated, its physiological basis would be indeterminate. The REM state is a configuration of physiological variables, the basis of which is a control mechanism that recruits and coordinates multiple sub-mechanisms into a stereotyped pattern. The diverse sub-mechanisms underlying each individual component of the REM state do not have an intrinsic relationship with the REM state itself. [Nielsen].

Mechanistic studies may be defined as ‘an experiment, using an intervention in healthy subjects or patients, to better understand human biology and/or disease’. Such studies provide useful physiological insights into clinical conditions in humans and expand our knowledge of physiology in health and disease. Well-planned mechanistic studies are therefore a vital step in progressing drug discovery in humans. It is important in such studies that the rights and safety of research participants are preserved, while at the same (...) time not allowing lengthy and complex approval procedures to stifle and potentially prohibit this type of research. (shrink)

This volume emphasizes the diversity and fruitfulness of early modern mechanism as a program, as a concept, as a model. Mechanistic study of the living body but also of the mind and mental processes are examined in careful historical focus, dealing with figures ranging from the first-rank (Bacon, Descartes, Spinoza, Cudworth, Gassendi, Locke, Leibniz, Kant) to less well-known individuals (Scaliger, Martini) or prominent natural philosophers who have been neglected in recent years (Willis, Steno, etc.). The volume moves from early (...) modern medicine and physiology to late Enlightenment and even early 19th-century psychology, always maintaining a conceptual focus. It is a contribution to a newly active field in the history and philosophy of early modern life science. It is of interest to scholars studying the history of medicine and the development of mechanistic theories. (shrink)

Sexually‐selected exaggerated traits tend to be unusually reliable signals of individual condition, as their expression tends to be more sensitive to nutritional history and physiological circumstance than that of other phenotypes. As such, these traits are the foundation for many models of sexual selection and animal communication, such as “handicap” and “good genes” models. Exactly how expression of these traits is linked to the bearer's condition has been a central yet unresolved question, in part because the underlying physiological mechanisms regulating (...) their development have remained largely unknown. Recent discoveries across animals as diverse as deer, beetles, and flies now implicate the widely conserved insulin‐like signaling pathway, as a common physiological mechanism regulating condition‐sensitive structures with extreme growth. This raises the exciting possibility that one highly conserved pathway may underlie the evolution of trait exaggeration in a multitude of sexually‐selected signal traits across the animal kingdom. (shrink)

Descartes’s mechanistic account of the passions is sometimes dismissed as one which lacks the resources toadequately explain the cognitive aspect of emotion. By some, he is taken to be “feeling theorist”, reducing thepassions to a mere awareness of the physiological state of the soul-body union. If this reading of Descartes’spassions is correct, his theory fails not only because it cannot account for the intentional nature of the passions,but also because the passions cannot play the role in Descartes’s moral theory (...) they are meant to play. I arguethat Descartes’s account is not best read as a feeling theory. I defend a reading of the Cartesian passions whichacknowledges their mechanistic nature, arguing that for Descartes, passions are modes of the soul withcognitive significance, they are perceptions of relational axiological properties. Thus, Descartes’s theory of thepassions has the resources to connect it with an account of good conduct. As a means of elaborating on thenormative nature of the passions I consider the role of generosity in Descartes’s moral theory. (shrink)

Descartes’s mechanistic account of the passions is sometimes dismissed as one which lacks the resources to adequately explain the cognitive aspect of emotion. By some, he is taken to be “feeling theorist”, reducing the passions to a mere awareness of the physiological state of the soul-body union. If this reading of Descartes’s passions is correct, his theory fails not only because it cannot account for the intentional nature of the passions, but also because the passions cannot play the role (...) in Descartes’s moral theory they are meant to play. I argue that Descartes’s account is not best read as a feeling theory. I defend a reading of the Cartesian passions which acknowledges their mechanistic nature, arguing that for Descartes, passions are modes of the soul with cognitive significance, they are perceptions of relational axiological properties. Thus, Descartes’s theory of the passions has the resources to connect it with an account of good conduct. As a means of elaborating on the normative nature of the passions I consider the role of generosity in Descartes’s moral theory. (shrink)

Apoptosis is a physiological mechanism for the removal of unwanted or damaged cells. Apoptotic cells are rarely seen in living tissues, however, because of their rapid and efficient removal by phagocytosis. Phagocytotic cells such as macrophages or dendritic cells recognize apoptotic cells by specific changes of cell surface markers, which usually are not present on normal cells. One such event is the exposure of phosphatidylserine, which moves from the plasma membrane inner leaflet to the outer leaflet in preapoptotic cells. An (...) unresolved problem, however, was the nature of the phosphatidylserine receptor on the phagocytotic cells. In a recent issue of Nature, Fadok et al.(1) have reported the cloning of a phosphatidylserine receptor using an antibody raised against activated macrophages. Antibody treatment of these macrophages blocks this capacity to engulf. BioEssays 22:878–881, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Marjorie Grene has argued in a number of contexts that any attempt to reduce the explanation of human actions to “mechanistic” explanations is doomed to failure in advance because it is absurd. “This argument examines the status of the reductivist thesis in its own terms and reduces it to absurdity …” ; “the attempt to reduce human purposive, or ‘intentional,‘ action to physiology and ultimately to physics and chemistry is an absurdity rather than simply a confusion”. I wish (...) to show that this argument is fallacious because it involves a petitio principii; and if Plato can be credited with introducing the same argument in the Theaetetus, as she suggests, so much the worse for Plato. (shrink)

In Gottfried Wilhelm Leibniz's time, micro-mechanism seemed to dominate, though not exclusively, the more innovative trend in physiology, and microscopic anatomy determined the representation of living beings. The basic postulate was that human understanding could rely on microscopic observation and account for microstructures by framing mechanical models: along that trend, hope was to attain the real causes of physiological phenomena. In his natural philosophy, Leibniz grants living beings a prominent place. His metaphysics contains arguments and notions that build on (...) physiological concepts to express the condition of finite substances and the relationship between substances in the phenomenal world. For Leibniz, at least in the later stages of his career, the account of living individuals and of their properties would provide access to a well-founded representation of corporeal substances in general. This article looks at Leibniz's views on physiology and organic bodies, focusing on his conception of living beings as "machines of nature" and his theory of monads. (shrink)

At the end of the nineteenth century, approaches from experimental physiology made inroads into embryological research. A new generation of embryologists felt urged to study the mechanisms of organ formation. This new program, most prominently defended by Wilhelm Roux, was called Entwicklungsmechanik. Named variously as “causal embryology”, “physiological embryology” or “developmental mechanics”, it catalyzed the movement of embryology from a descriptive science to one exploring causal mechanisms. This article examines the specific scientific and epistemological meaning of the mechanistic (...) approaches of embryological development by focusing on Wilhelm His’ histogenetic work. Roux was neither the first, nor the only one to argue for an experimental exploration of causes in embryology. At the time of Roux, physiological explanations of the genesis of the anatomical forms were developing in parallel, not only in German-speaking countries, but in France, Switzerland and English-speaking countries as well. The experimental approach and the cellular descriptions of embryogenesis were already omni-present when Roux proposed his Entwicklungsmechanik. However, these approaches remained disjointed. It appears that it was Wilhelm His who first succeeded in combining the question of the causal factors determining epigenesis, which was closely connected with experimentation on, and cellular descriptions of, development, in a coherent and concrete synthesis, making him one of the true initiators of the developmental mechanics. (shrink)

A common and enduring early modern intuition is that materialists reduce organisms in general and human beings in particular to automata. Wasn’t a famous book of the time entitled L’Homme-Machine? In fact, the machine is employed as an analogy, and there was a specifically materialist form of embodiment, in which the body is not reduced to an inanimate machine, but is conceived as an affective, flesh-and-blood entity. We discuss how mechanist and vitalist models of organism exist in a more complementary (...) relation than hitherto imagined, with conceptions of embodiment resulting from experimental physiology. From La Mettrie to Bernard, mechanism, body and embodiment are constantly overlapping, modifying and overdetermining one another; embodiment came to be scientifically addressed under the successive figures of vie organique and then milieu intérieur, thereby overcoming the often lamented divide between scientific image and living experience. (shrink)

We may now ask the question: In what historical perspective should we place the work of Richard Goldschmidt? There is no doubt that in the period 1910–1950 Goldschmidt was an important and prolific figure in the history of biology in general, and of genetics in particular. His textbook on physiological genetics, published in 1938, was an amazing compendium of ideas put forward in the previous half-century about how genes influence physiology and development. His earlier studies on the genetic and (...) geographic distribution of the various species and races of Lymantria contributed soundly to an understanding of the inheritance and development of sex, as well as the genetics of speciation. He was a curious mixture of the experimentalist, empiricist, and theorizer, who could grasp both the large and the small at once and wrap them into the same integrated and coherent package.In insisting on trying to relate genetics to development, Goldschmidt was continually forced to speculate and to forsake experimental fact for generalized theory. In refusing to reconcile a physiological and developmental conception with a corpuscular theory of the gene, he forced himself to substitute for a large body of experimentally verified evidence, vague and general speculations which did not lead in any precise direction. L. C. Dunn summarizes succinctly the effect of Goldschmidt's thinking on the development of genetic theory: Although Goldschmidt's ideas had a considerable influence in directing attention to the developmental processes intervening between genes and characters, they did not lead to the establishment of a general theory of development in genetical terms. In fact, at the end of the period, as signalized by Goldschmidt's book of 1938 [Physiological Gentics] doubt remained whether there was a field with a defined problem which could be identified as developmental genetics.Yet the frequency with which Goldschmidt is cited by later writers suggests that there is a more positive side to his contribution than this. The early Mendelians had recognized the genic constitution of organisms and the Drosophila workers had uncovered in detail the chromosomal mechanism of heredity. These great discoveries were of classical character, solidly based on a multitude of well established facts. By themselves, however, they would not have been sufficient to place genetics in the central position within biology which it was to assume. Beyond the “static” analysis of gene transmission an insight was needed into the dynamic role of genes in cellular physiology, biochemistry, and development. Goldschmidt recognized this aspect and outlined in brilliant generalizations a physiological theory of genetics. Necessarily the prophetic nature of this achievement — romantic in the sense of Ostwald's classification of great scientists and their discoveries — transcended its factual basis. It was the audacity of the theoretician unimpeded by the still scanty data which gave a new focus to biological thought.Some have called Goldschmidt an “obstructionist” in the history of genetics—one whose efforts were largely directed toward useless and continual criticism — challenge for the sake of challenge. As this line of argument goes, time wasted answering Goldschmidt's poorly conceived criticisms could have been better used to pursue new lines of thought within the classical gene theory. Sometimes historians are upbraided for studying the work of such “obstructionists,” or even the work of those whose ideas have later proved to be inadequate. This argument misses the point of history and the lessons which it can teach. Perhaps Goldschmidt did take the time of a number of the classical geneticists who tried to answer his objections to the gene theory; and perhaps many of his own ideas about genes were, by today's view, “wrong.” These are always easier judgments to make by hindsight than at the moment. But that is not the point. Goldschmidt had a considerable influence on his contemporaries, and to dismiss him as an obstructionist because his opponents later proved to be more nearly right, distorts history and obscures significant questions which we might well be asking. It might be valuable to know why Goldschmidt felt compelled to be an iconoclast —and how that impulse, psychological in orgin, led him to overlook critical items of evidence which his opponents considered more carefully. It might also be valuable to try and understand how a contemporary of Goldschmidt or. Morgan really viewed the gene theory — what were its strong and weak point? Such questions are not readily answered by studying the work of only those men who were correct by later standards.Answers to some of the above questions can be gleaned from this study of Goldschmidt — though the first, and most psychologically oriented, question is largely untouched here.On the one hand, Goldschmidt forced classical geneticists to reexamine the foundation of their ideas about the nature, inviolability, and even physical dimensions of genes. He also kept alive the very real problems of gene physiology and its relations to development — a relationship that was given less attention by the Drosophila school in their pursuit of the transmission process. On a broader level he emphasized to the biological community a principle that was in danger of being lost in the enthusiasm surrounding the expansion of the Mendelian-chromosome theory. The point was that all theories in science are transient, logical constructs which should not be held as sacred. Time and again, as the history of science has shown, theories become rigid structures which retard new modes of thought. From Goldschmidt's perspective, the gene theory was in danger of performing just that function, for it was preventing workers from viewing the gene in a functional as well as a structural light.On the other hand, examining the work of critics (or even of outright “obstructionists”) gives the historian an opportunity to observe how the more established community of scholars at some point in time reacts to challenges of its cherished ideas. The fact that many workers in his own day (such as Beadle, Luria, Delbruck, Sturtevant, Bridges, and others), as well as most geneticists today, saw Goldschmidt as having been largely “obstructionist” is useful historical (and/or sociological) data. Clearly, as this paper has tried to show, Goldschmidt's ideas were not all obstructionist, and his viewpoint that genes must be considered functionally was one which was clearly valid, premature as it may have been from an experimental and technique point of view. Perhaps Goldschmidt's major fault was that he developed alternative theories which were not easily testable. Nonetheless, his challenge to a fundamental and established idea brought forth a reaction from many members of the genetic community which indicates how unwilling they were to reconsider the formalized theory on which their work was based. While many of Goldschmidt's criticisms — and particularly his way of making them — arose out of his own idiosyncrasies, they were also a product of his times. His view of the nature of theory-construction, and his rejection of old-style reductionism and mechanism, were part of a growing awareness within the world scientific community that explanations based on reducing complex phenomena to ultimate particles or units were clearly inadequate. The success of the Mendelian-chromosome theory had obscured that fact for many geneticists, but to Goldschmidt it was a point that could not be allowed to pass unnoticed. (shrink)

The topic of disease mechanisms is of clinical importance, as our understanding of such mechanisms plays an important role in how we approach devising treatments for disease. In this paper, I critique an argument made by Mauro Nervi, in which he asserts that pathology is often better viewed in the context of distinct theoretical mechanisms. I use this critique as a starting point to argue that viewing pathology as a broken-normal, malfunctioning mechanism is more therapeutically practical and more relevant to (...) clinical drug design, than creating a theoretical separation of pathology from physiology. (shrink)

Beginning in the mid-1930s the comparative physiologists Laurence Irving and Per Fredrik Scholander pioneered the study of diving mammals, particularly harbor seals. Although resting on earlier work dating back to the late nineteenth century, their research was distinctive in several ways. In contrast to medically oriented physiology, the approaches of Irving and Scholander were strongly influenced by natural history, zoology, ecology, and evolutionary biology. Diving mammals, they argued, shared the cardiopulmonary physiology of terrestrial mammals, but evolution had modified (...) these basic adaptive processes in extreme ways. In particular, seals’ remarkable ability to hold breath, lower metabolism, produce energy anaerobically, and resist asphyxiation, provided a sharp contrast with terrestrial mammals, including humans. This diving physiology was an extreme elaboration of a general regulatory mechanism that allowed seals and other diving mammals to remain active underwater for extended periods. The decrease in heart rate referred to as bradycardia or the “diving reflex” was highly developed in diving mammals, but also found in less developed form in many other organisms faced by asphyxia. It therefore served as a kind of “master switch” for lowering metabolism in diving, hibernation, parturition, drowning, and other physiological responses involving lack of oxygen. Studying bradycardia unified a wide diversity of physiological phenomena, while also providing a context for contrasting the physiological responses of various species, including humans. Conducted in the laboratory and the field, this research served as a bridge between a comparative physiological ecology focused on non-human species and a human-centered general physiology. (shrink)

Some natural philosophers in the 17th century believed that they could control their own innards, specifically the animal spirits coursing incessantly through brain and nerves, in order to discipline or harness passion, cognition and action under rational guidance. This chapter addresses the mechanisms thought necessary after Eden for controlling the physiology of passion. The tragedy of human embedding in the body, with its cognitive and moral limitations, was paired with a sense of our confinement in sequential time. I use (...) two strands of 17th-century natural philosophy to exemplify forms of the perceived connection between physiology, memory, and the passions. I deal at length with Cartesian mechanism, and more briefly with Restoration natural philosophy in England. These are fruitful historical domains for connecting cognition and culture, since relations of domination, disruption, or accommodation between present and past are in play for both selves and societies. Despite the difficulty of integrating affect with cognition in theories of brain and mind, the capacity to treat passion and memory together is crucial for future cognitive science to address issues which outsiders care about. (shrink)

This paper focuses on an understudied aspect of Hobbes's natural philosophy: his approach to the domain of life. I concentrate on the role assigned by Hobbes to the heart, which occupies a central role in both his account of human physiology and of the origin of animal locomotion. With this, I have three goals in mind. First, I aim to offer a cross-section of Hobbes's effort to provide a mechanistic picture of human life. Second, I aim to contextualize (...) Hobbes's views in the seventeenth-century debates on human physiology and animal locomotion. In particular, I will compare Hobbes's views with the theories put forth by Harvey, Descartes, the Galenic, and Peripatetic traditions. Also, I will show that Hobbes was receptive to advances within contemporary English physiology and chemistry. Third, by means of a comparison with Descartes, I advance some hypothesis to explain why Hobbes indentified the heart, and not the brain (as was increasingly com... (shrink)

Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus (...) was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena – structures, processes or the mechanisms that explain them – through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes. (shrink)

At fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+ concentration. The precise sequence of events that occur between sperm‐egg contact and the increases in intracellular Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that (...) specifically comigrates with Ca2+ oscillation‐inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+ oscillations may have wider physiological significance since sperm oscillin can induce Ca2+ oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations. (shrink)

Oxygenated derivatives of cholesterol (oxysterols) are widely distributed in nature, being found in the blood and tissues of animals and man as well as in foodstuff. They exhibit many biological activities which are of potential physiological, pathological or pharmacological importance. Many oxysterols have been found to be potent inhibitors of cholesterol biosynthesis and one or more oxysterols may play a role as the physiologic feedback regulator of cholesterol synthesis. Oxysterols also inhibit cell replication and have cytotoxic properties effects which suggest (...) that these sterols may participate in the regulation of cell proliferation and may be potentially useful as therapeutic agents for cancer. Furthermore, there is considerable evidence that oxysterols may be involved in the pathogenesis of atherosclerosis. Although the mechanism of action of oxysterols in all these instances is not well understood, the existence of cytosolic and microsomal proteins which bind oxysterols with high affinity and specificity suggests that this group of compounds may represent a family of intracellular regulatory molecules. (shrink)

Cowan makes an intriguing case for a fundamental limit in the number of chunks that can be stored in short term memory. Chunks are collections of concepts that have strong associations to one another and much weaker associations to other chunks. A translation of this definition for the visual domain would be that a visual chunk is a collection of features that belong to the same perceptual group. Here, we will first address the neuronal mechanisms that may demarcate visual chunks. (...) Then we critically evaluate to what extent these mechanisms might be responsible for the limit on the number of chunks that can be held in STM. We conclude that the clarity with which the psychophysical data point to the number four is not matched by a similarly clear limit imposed by physiological mechanisms. (shrink)

Steroid‐hormone‐activated receptor proteins are among the best‐understood class of factors for altering gene transcription in cells. Steroid receptors are of major importance in maintaining normal human physiology by responding to circulating concentrations of steroid in the nM range. Nonetheless, most studies of steroid receptor action have been conducted using the supra‐physiological conditions of saturating concentrations (≥100 nM) of potent synthetic steroid agonists. Here we summarize the recent developments arising from experiments using two clinically relevant conditions: subsaturating concentrations of agonist (...) (to mimic the circulating concentrations in mammals) and saturating concentrations of antagonists (which are employed in endocrine therapies to block the actions of endogenous steroids). These studies have revealed new facets of steroid hormone action that could not be uncovered by conventional experiments with saturating concentrations of agonist steroids, such as a plethora of factors/conditions for the differential control of gene expression by physiological levels of steroid, a rational approach for examining the gene‐specific variations in partial agonist activity of antisteroids, and a dissociation of steroid potency and efficacy that implies the existence of separate, and possibly novel, mechanistic steps and cofactors. BioEssays 30:744–756, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This paper argues that, contrary to the claims of Alan Chalmers, Boyle understood his experimental work to be intimately related to his mechanical philosophy. Its central claim is that the mechanical philosophy has a heuristic structure that motivates and gives direction to Boyle's experimental programme. Boyle was able to delimit the scope of possible explanations of any phenomenon by positing both that all qualities are ultimately reducible to a select group of mechanical qualities and that all explanations of natural phenomena (...) are to be in terms of the operations of machines and are to appeal only to qualities that are already familiar. This is illustrated by his investigations into the Torricellian experiment. Boyle's explanation of the elevation of the mercurial cylinder by appeal to the spring of the air was an intermediate mechanical explanation. Boyle was convinced that the spring of the air was ultimately reducible to the mechanical qualities. This in turn had implications for his research into the cause of respiration. In a move that was both parsimonious and consistent with the broad requirements of the mechanical philosophy, Boyle was able to solve the problem of the cause of the inflow of air into the lungs by appeal to his research in pneumatics. This application of a mechanical explanation in pneumatics to physiology is just what one would expect if the mechanical philosophy was as universal as Boyle claimed it to be. Therefore, far from Boyle's experiments having a life of their own, they were clearly directed by and understood in terms of the mechanical philosophy.Keywords: Air-pump; Boyle; Chalmers; Experiment; Explanation; Mechanism. (shrink)

Parvalbumins (PVs) are acidic, intracellular Ca2+‐binding proteins of low molecular weight. They are associated with several Ca2+‐mediated cellular activities and physiological processes. It has been suggested that PV might function as a “Ca2+ shuttle” transporting Ca2+ from troponin‐C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus, PV may contribute to the performance of rapid, phasic movements by accelerating the contraction–relaxation cycle of fast‐twitch muscle fibers. Interestingly, PVs promote the generation of power stroke in fish by speeding (...) up the rate of relaxation and thus provide impetus to attain maximal sustainable speeds. However, immunological monitoring of diverse tissues demonstrated that PVs are also present in non‐muscle cells. The axoplasmic transport and various intracellular secretory mechanisms including the endocrine secretions seem to be controlled by the Ca2+ regulation machinery. Any defect in the Ca2+ handling apparatus may cause several clinical problems; for instance, PV deficiency alters the neuronal activity, a key mechanism leading to epileptic seizures. Moreover, atypical relaxation of the heart results in diastolic dysfunction, which is a major cause of heart failure predominantly among the aged people. PV may offer a unique potential to correct defective relaxation in energetically compromised failing hearts through PV gene transfer. Consequently, PV gene transfer may present a new therapeutic approach to correct cellular disturbances in Ca2+ signaling pathways of diseased organs. Hence, PVs appear to be amazingly useful candidate proteins regulating a variety of cellular functions through action on Ca2+ flux management. (shrink)

This paper examines the implications of the Doctrine of Specific Nerve Energies for contemporary philosophy and psychology. Part I analyzed Johannes Peter Muller’s canonical formulation of the Doctrine, arguing that it follows from empirical results combined with methodological principles. Here, I argue that these methodological principles remain valid in psychology today, consequently, any naturalistic philosophy of perception must accept the Doctrine’s skeptical conclusion, that the qualities of our perceptual experience are not determined by, and thus do not reveal the nature (...) of, their causes in the world. Nevertheless, this does not mean that we must be global skeptics; rather, I argue that contemporary epistemology of perception should embrace Muller’s own response to the Doctrine: epistemic structural realism. As articulated by Muller’s student, Helmholtz, structural realism follows from the Doctrine once we recognize that active exploration constitutes part of the mechanism that determines perceptual experience, a view congenial to contemporary theories of embodied perception in cognitive science. Structural realists in philosophy of science should likewise heed the lessons of the Doctrine, as it played a critical part in the early history of their view, and may still serve a constructive role as exemplar today. (shrink)

ArgumentEvery new level achieved by technology attracted the attention of physiologists and turned their thoughts in a new direction; they often unwittingly modeled life processes in the image of contemporary engineering achievements.–This article reinterprets the debate between orthodox followers of the Pavlovian reflex theory and Soviet “cybernetic physiologists” in the 1950s and 60s as a clash of opposing man-machine metaphors. While both sides accused each other of “mechanistic,” reductionist methodology, they did not see anything “mechanistic” about their own (...) central metaphors: the telephone switchboard metaphor for nervous activity, and the analogies between the human body and a servomechanism and between the human brain and a computer. I argue that the scientific utility of machine analogies was closely intertwined with their philosophical and political meanings and that new interpretations of these metaphors emerged as a result of political conflicts and a realignment of forces within the scientific community and in society at large. I suggest that the constant travel of man-machine analogies back and forth between physiology and technology has blurred the traditional categories of the “mechanistic” and the “organic” in Soviet neurophysiology, as perhaps in the history of physiology in general. (shrink)

The crystal δ‐endotoxins of Bacillus thuringiensis (Bt) are a family of insecticidal proteins which have been known for some time to kill insects by lysing their gut epithelial cells, but the precise molecular mechanism of toxicity has remained elusive. The recent publication of the crystal structure of a Bt δ‐endotoxin has made it possible for us to model the molecular events that occur as the toxin binds to its receptor and inserts into the membrane to form a pore. Using our (...) knowledge of insect gut physiology, we can also predict the effect on the insect of the formation of a toxic pore. We present a new model to explain the events that occur in the insect gut during toxin action. (shrink)

In the first decades of the twentieth century, the process of photosynthesis was still a mystery: Plant scientists were able to measure what entered and left a plant, but little was known about the intermediate biochemical and biophysical processes that took place. This state of affairs started to change between the two world wars, when a number of young scientists in Europe and the United States, all of whom identified with the methods and goals of physicochemical biology, selected photosynthesis as (...) a topic of research. The protagonists had much in common: They had studied physics and chemistry (although not necessarily plant physiology) to a high level; they used physicochemical methods to study the basic processes of life; they believed these processes were the same, or very similar, in all life forms; and they were affiliated with institutions that fostered this kind of study. This set of cognitive, methodological, and material resources enabled these protagonists to transfer their knowledge of the concepts and techniques from microbiology and human biochemistry, for example, to the study of plant metabolism. These transfers of knowledge had a great influence on the way in which the biochemistry and biophysics of photosynthesis would be studied over the following decades. Through the use of four historical cases, this paper analyzes these knowledge transfers, as well as the investigative pathways that made them possible. (shrink)

Understanding the evolutionary role of environmentally induced phenotypic variation (i.e., plasticity) is an important issue in developmental evolution. A major physiological response to environmental change is cellular stress, which is counteracted by generic stress reactions detoxifying the cell. A model, stress‐induced evolutionary innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types, is described. Previous findings suggest that the cell differentiation cascade of a cell type (...) critical to pregnancy in humans, the decidual stromal cell, evolved from a cellular stress reaction. It is hypothesized that the stress reaction in these cells was elicited ancestrally via inflammation caused by embryo attachment. The present study proposes that SIEI is a distinct form of plasticity‐based evolutionary change leading to the origin of novel structures rather than adaptive transformation of pre‐existing characters. (shrink)

In 1872, Emil du Bois-Reymond delivered an astonishing lecture entitled “The Limits of Science” at a Congress of German Scientists and Physicians in Leipzig. No stranger to polemic and bellicose oratory, and possessing among his generation of physiologists unmatched rhetorical abilities, du Bois-Reymond had already attracted much public recognition and acclaim for his denigration of French culture at a time when belligerence and competition between Prussia and France had peaked. Yet, the topic of his 1872 lecture had a signal significance (...) which not only would inform du Bois-Reymond’s subsequent public lectures on literature, art, civilization and science, and the place of Darwin in the modern world, but would also elaborate a mechanistic and fatalistic view of consciousness, one that denied scientific understanding of the phenomenon as even obtainable. Controversy exploded—and from all quarters. Renowned scientists accused him of pessimism and of failing to apprehend the progress of in .. (shrink)

Autonomous sensory meridian response (ASMR) and affective touch (AT) are two phenomena that have been independently investigated from separate lines of research. In this article, I provide a unified theoretical framework for understanding and studying them as complementary processes. I highlight their shared biological basis and positive effects on emotional and psychophysiological regulation. Drawing from evolutionary and developmental theories, I propose that ASMR results from the development of biological mechanisms associated with early affiliative behaviour and self‐regulation, similar to AT. I (...) also propose a multimodal interoceptive mechanism underlying both phenomena, suggesting that different sensory systems could specifically respond to affective stimulation (caresses, whispers and affective faces), where the integration of those inputs occurs in the brain's interoceptive hubs, allowing physiological regulation. The implications of this proposal are discussed with a view to future research that jointly examines ASMR and AT, and their potential impact on improving emotional well‐being and mental health. (shrink)

Major strands of the history of scientific psychology proposed less mechanistic explanations of behavior than the “series of billiard ball reactions” that Ellis ascribes to them. I tease apart psychological systems based on hedonism and those based on stimulus-response mechanisms-and then tease apart basic hedonism and drive-reduction hedonism, to layout psychological and neuroscientific foundations for the active, dynamic, cognitive, emotive, and "spiritual" dynamics of human nature which Ellis calls us to affirm. I trace these distinctions through the drive-reduction psychoanalysis (...) of Freud, the drive-reduction behaviorism of Hull, and the non-drive-reductive hedonistic system of Skinner. Then I trace the recent neuroscience of reward and punishment circuits and putative narcissistic and altruistic circuits, to conclude that Behaviorism and Neuroscience support broad hedonistic but major non-drive-reduction motivational systems. I affirm Ellis’ contention that emotions are basically “active”, although with some caveats and questions. (shrink)

This paper argues that, contrary to the claims of Alan Chalmers, Boyle understood his experimental work to be intimately related to his mechanical philosophy. Its central claim is that the mechanical philosophy has a heuristic structure that motivates and gives direction to Boyle's experimental programme. Boyle was able to delimit the scope of possible explanations of any phenomenon by positing both that all qualities are ultimately reducible to a select group of mechanical qualities and that all explanations of natural phenomena (...) are to be in terms of the operations of machines and are to appeal only to qualities that are already familiar. This is illustrated by his investigations into the Torricellian experiment. Boyle's explanation of the elevation of the mercurial cylinder by appeal to the spring of the air was an intermediate mechanical explanation. Boyle was convinced that the spring of the air was ultimately reducible to the mechanical qualities. This in turn had implications for his research into the cause of respiration. In a move that was both parsimonious and consistent with the broad requirements of the mechanical philosophy, Boyle was able to solve the problem of the cause of the inflow of air into the lungs by appeal to his research in pneumatics. This application of a mechanical explanation in pneumatics to physiology is just what one would expect if the mechanical philosophy was as universal as Boyle claimed it to be. Therefore, far from Boyle's experiments having a life of their own, they were clearly directed by and understood in terms of the mechanical philosophy. (shrink)

A mathematical model based upon catastrophe theory is derived to describe the kinematics of the wing beat in Dipteran flight. The parameters of the model correspond to anatomical and physiological characteristics of the insect.

Diffusion theory explains in physical terms how materials move through a medium, e.g. water or a biological fluid. There are strong and widely acknowledged grounds for doubting the applicability of this theory in biology, although it continues to be accepted almost uncritically and taught as a basis of both biology and medicine. Our principal aim is to explore how this situation arose and has been allowed to continue seemingly unchallenged for more than 150 years. The main shortcomings of diffusion theory (...) will be briefly reviewed to show that the entrenchment of this theory in the corpus of biological knowledge needs to be explained, especially as there are equally valid historical grounds for presuming that bulk fluid movement powered by the energy of cell metabolism plays a prominent note in the transport of molecules in the living body. First, the theory's evolution, notably from its origins in connection with the mechanistic materialist philosophy of mid nineteenth century physiology, is discussed. Following this, the entrenchment of the theory in twentieth century biology is analyzed in relation to three situations: the mechanism of oxygen transport between air and mammalian tissues; the structure and function of cell membranes; and the nature of the intermediary metabolism, with its implicit presumptions about the intracellular organization and the movement of molecules within it. In our final section, we consider several historically based alternatives to diffusion theory, all of which have their precursors in nineteenth and twentieth century philosophy of science. (shrink)