Skeletal muscle formation is studied in vitro with myogenic cell lines and primary muscle cell cultures, and in vivo with embryos of several species. We review several of the notable advances obtained from studies of cultured cells, including the recognition of myoblast diversity, isolation of the MyoD family of muscle regulatory factors, and identification of promoter elements required for muscle‐specific gene expression. These studies have led to the ideas that myoblast diversity underlies the formation of the multiple types of (...) fast and slow muscle fibers, and that myogenesis is controlled by a combination of ubiquitous and muscle‐specific transcriptional regulators that may be different for each gene. We further review some unexpected results that have been obtained when ideas from work in culture have been tested in developing animals. The studies in vivo point to additional molecular and cellular mechanisms that regulate muscle formation in the animal. (shrink)

Amphibians that undergo a metamorphosis provide an unparalleled opportunity to investigate how skeletal shape is generated, preserved, and transformed in development. Their pharyngeal arch (PA) cartilages, which support breathing and feeding behaviors, form embryonically from cranial neural crest cells, grow isometrically at larval stages, and abruptly change shape during metamorphosis. Further, the shape changes occur in three different ways: some adult cartilages form de novo, others emerge from within resorbing larval cartilages and some larval cartilages reshape themselves at (...) the cellular level. Isometric growth followed by abrupt shape change is unique to amphibian PA cartilages, which suggests that the origin and evolution of amphibian metamorphosis has been influenced by the tissue properties of cartilage. This essay reviews the functional role of the PA skeleton in frogs and salamanders and presents a mechanistic framework for understanding how its shape is generated, preserved, and transformed at the levels of cell behavior and specification mechanisms. (shrink)

In humans, there are two skeletal muscle α‐actinins, encoded by ACTN2 and ACTN3, and the ACTN3 genotype is associated with human athletic performance. Remarkably, approximately 1 billion people worldwide are deficient in α‐actinin‐3 due to the common ACTN3 R577X polymorphism. The α‐actinins are an ancient family of actin‐binding proteins with structural, signalling and metabolic functions. The skeletal muscle α‐actinins diverged ∼250–300 million years ago, and ACTN3 has since developed restricted expression in fast muscle fibres. Despite ACTN2 and ACTN3 (...) retaining considerable sequence similarity, it is likely that following duplication there was a divergence in function explaining why α‐actinin‐2 cannot completely compensate for the absence of α‐actinin‐3. This paper focuses on the role of skeletal muscle α‐actinins, and how possible changes in functions between these duplicates fit in the context of gene duplication paradigms. (shrink)

Cytoskeletal organization in embryonic skeletal muscle cells has been examined by transmission electron microscopy; the technique involves preparation using the platinum replication method of freezedried samples, with and without cryofracture. The cytoskeletons in developing muscle cells appear to play a role in preserving cell shape as well as in anchoring myofibrils to cell membrane.

It has been commonly claimed that prehistoric warfare in Japan began in the Yayoi period. Population increases due to the introduction of agriculture from the Korean Peninsula to Japan resulted in the lack of land for cultivation and resources for the population, eventually triggering competition over land. This hypothesis has been supported by the demographic data inferred from historical changes in Kamekan, a burial system used especially in the Kyushu area in the Yayoi period. The present study aims to examine (...) the previous claim by using an expanded dataset of human skeletal remains and Kamekan. First, in order to quantify the intensity of warfare, we developed a database of injured individuals found in the middle phase of the Yayoi period in two large populations in the northern Kyushu area, the Fukuoka plain and the upperand middle-stream of the Homan River. Second, we collected Kamekan data from site reports published after 1990 and constructed a comprehensive database to infer the demography in these areas. Finally, we compared the frequency of injured individuals and the inferred demography. The results suggest that the frequency of injured individuals and the population increase tended to be higher at the upper- and middle-stream of the Homan River than on the Fukuoka plain. Different assumptions of the lifetime of each type of Kamekan can produce mixed results on the relationship between demography and the frequency of injured individuals. They were positively correlated under the traditional assumption of constant time intervals, while there was no correlation using time intervals based on carbon dating by the National Museum of Japanese History. Thus, our results are partially consistent with the previous claim that the population increase and the lack of land and resources due to the introduction of agriculture were causes of warfare in the northern Kyushu area in the middle phase of the Yayoi period. (shrink)

Despite decades of research, remaining safety concerns regarding disease transmission, heterotopic tissue formation, and tumorigenicity have kept stem cell‐based therapies largely outside the standard‐of‐care for musculoskeletal medicine. Recent insights into trophic and immune regulatory activities of mesenchymal stem cells (MSCs), although incomplete, have stimulated a plethora of new clinical trials for indications far beyond simply supplying progenitors to replenish or re‐build lost/damaged tissues. Cell banks are being established and cell‐based products are in active clinical trials. Moreover, significant advances have also (...) been made in the field of pluripotent stem cells, in particular the recent development of induced pluripotent stem cells. Their indefinite proliferation potential promises to overcome the limited supply of tissue‐specific cells and adult stem cells. However, substantial hurdles related to their safety must be overcome for these cells to be clinically applicable. (shrink)

Gene targeting has allowed the dissection of complex biological processes at the genetic level. Our understanding of the nuances of skeletal muscle development has been greatly increased by the analysis of mice carrying targeted null mutations in the Myf‐5, MyoD and myogenin genes, encoding members of the myogenic regulatory factor (MRF) family. These experiments have elucidated the hierarchical relationships existing between the MRFs, and established that functional redundancy is a feature of the MRF regulatory network. Either MyoD or (...) Myf‐5 is sufficient for the formation or survival of skeletal myoblasts. Myogenin acts later in development and plays an essential in vivo role in the terminal differentiation of myotubes. (shrink)

Ubiquitin is the most phylogenetically conserved protein known. This 8,500 Da polypeptide can be covalently attached to cellular proteins as a posttranslational modification. In most cases, the addition of multiple ubiquitin adducts to a protein targets it for rapid degradation by a multisubunit protease known as the 26S proteasome. While the ubiquitin/26S proteasome pathway is responsible for the degradation of the bulk of cellular proteins during homeostasis, it may also be responsible for the rapid loss of protein during the programmed (...) death of certain cells, such as skeletal muscle during insect metamorphosis. In addition, alterations in the expression and regulation of ubiquitin may play significant roles in pathological disorders. For example, dramatic increases in ubiquitin and ubiquitin‐protein conjugates are observed in a wide variety of neurodegenerative disorders, including Alzheimer's disease. Patients suffering from the autoimmune disease systemic lupus erythematosus generate antibodies reacting with ubiquitin and ubiquitinated histones. At present, it is not known whether these changes in ubiquitin expression and regulation initiate pathological changes in these diseases or if they are altered as a consequence of these disorders. (shrink)

During vertebrate limb development, various genes of the Hox family, the products of which influence skeletal element identity, are expressed in specific spatiotemporal patterns in the limb bud mesenchyme. At the same time, the cells also exhibit ‘self‐organizing’ behavior – interacting with each other via extracellular matrix and cell‐cell adhesive molecules to form the arrays of mesenchymal condensations that lead to the cartilaginous skeletal primordia. A recent study by Yokouchi et al.(1) establishes a connection between these phenomena. (...) They misexpressed the product of the Hoxa‐13 gene in chick limb buds and demonstrated both skeletal pattern perturbations and changes in cell‐cell adhesivity in mesenchyme aberrantly expressing this protein. (shrink)

The author of the Yogav sistha Mah r m yana has liberation (moksa) foremost on her or his mind and this focus appears to relegate virtue (dharma) to poor relation status. Yet, R ma's question to Vasistha is, 'How should one live in this world?' This signals a strongly ethical stance and opens another avenue of exploration; the possibility that the teachings on the realisation of liberation are concomitant with the teachings regarding the embodiment of virtue. The aim of this (...) paper is to flesh out the admittedly skeletal frame of virtue by comparing the theories in the Yogav sistha with Aristotle's elaboration of virtue in the Nicomachean Ethics. I argue that, in spite of fundamental metaphysical differences between the two philosophers, the stages of moral development described in the Yogav sistha harmonise with Aristotle's theories and provide insights into problems that arise in Aristotle's work. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Human Life is Radical Reality: An Idea Developed from the Conceptions of Dilthey, Heidegger, and Ortega y GassetBob SandmeyerHoward N. Tuttle. Human Life is Radical Reality: An Idea Developed from the Conceptions of Dilthey, Heidegger, and Ortega y Gasset. New York: Peter Lang, 2005. Pp. x + 200. Cloth, $59.95.This is a book which seeks to sketch out a coherent philosophy of life. By arguing that "human life (...) is radical reality," Professor Tuttle places the ontological priority of "my life" over and against that of every reality encountered in that life. Yet the life at issue in this book is no solus ipse, and the things or pragmata of this life do not therefore depend on the I for their being. As Ortega y Gasset asserts, I am myself and my circumstances. Neither subject nor substance exists independently of the other. As such, each bears the mark of this bi-polarity (40, 45). Hence human life, "my life," is not conceived here as a subjective immanence but rather as a carnate life that projects itself, i.e., its possibilities, into the concrete situation of its worldly circumstances. Indeed, the narrative structure of this projection expresses a central categorical feature of human life, its historicity. "Human life becomes here conceived as the historical stream of the inner and outer, the 'I' and its world" (155). Every reality takes its meaning from—in truth, has its status as a transcendent reality from—the manner and the guise in which it appears within the narrative of this self-construction of my life (5, 26, 40, 45, 88, 156, 171). This is a thesis, Tuttle argues, that has its roots in the writings of three figures: Wilhelm Dilthey, to whom the author refers as the "founder of the philosophy of human life," Martin Heidegger, the famous German philosopher whose explication of the structure of Dasein is central to the situated intersubjectivity of "my life" articulated in this book, and José Ortega y Gasset, the Spanish philosopher whose writings arguably play the most central role in the work (6, 26, 142, 155, 166).Professor Tuttle ought to be commended for the breadth of his undertaking and the economy of his presentation. Given its ambition, this is a short work of no more than 179 pages excluding notes and bibliography. This pithiness and a general lack of technical jargon speak well of the work, especially as it seems likely to find its way into the hands of young scholars interested in existential phenomenology, Lebensphilosophie, and continental philosophy generally. Indeed, within this broad field there are too few efforts like this one which seek to examine the interconnection of these three philosophers. Yet the very attributes that make this book a favorable addition to any collection also contribute to a serious defect in the work. Where its brevity demands precise articulation, the book often falls into repetition. The discussion of the distinction between clock time and lived time, for instance, comes across as especially belabored. Throughout the work, there are passages which appear virtually identical in different sections. And where its accessible presentation offers an easy introduction to some very difficult material, its lack of focus leaves one to wonder about the efficacy of its message. As Professor Tuttle remarks in the last lines of the work, "this essay is at very best only a collection of abstract and skeletal thought forms that have been generated within my life in its relation to its circumstances" (178).Reading the work, then, one wonders if it is best suited for the young scholar, the accomplished academic, or both. A lack of sufficient background footnoting restricts the acceptability of this work as a tool for serious research. For instance, given the aims of the book one would expect that Heidegger's lectures on "Wilhelm Dilthey's Research and the Struggle for a Historical Worldview" would have a prominent role in the essay, yet it is not even cited. The essay thus seems best directed towards more novice scholars. Yet the skeletal feel of the work and the unfocused integration of many of the themes from the different writings of Dilthey, Heidegger, and Ortega y Gasset... (shrink)

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non‐endosteal perisinusoidal niche. Single‐cell molecular profiling and in vivo cell lineage analyses play key roles (...) in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor‐making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast‐chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell‐like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation. (shrink)

The development of the vertebrate skeleton is under complex genetic control, and good progress is being made towards identifying the genes responsible. A recent paper(1) contributes to this progress by describing transgenic mice in which the homeobox‐containing MHox gene has been disrupted. MHox(−/−) mice have a range of skeletal defects, involving loss or shortening of structures in the skull, face and limb. Puzzling features of the MHox(−/−) mutation, which has similar effects on bones with very different embryological origins (...) and yet spares other bones completely, may hold clues to the mechanisms that shape the skeleton. MHox(−/−) mice, used in conjunction with other skeletal mutants, will be important tools for exploring these mechanisms further. (shrink)

Skeletal myoblasts have their origin early in embryogenesis within specific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle‐specific phenotype after they have received the appropriate environmental signals. Once proliferating myoblasts enter the differentiation programme they withdraw from the cell cycle and form post‐mitotic multinucleated myofibres (myogenesis); this transformation is accompanied by muscle‐specific gene expression. Muscle development is associated with complex and diverse protein isoform transitions, generated by differential gene expression (...) and mRNA splicing. The myofibres are in a state of dynamic adaptation in response to hormones, mechanical activity and motor innervation, which modulate differential gene expression and splicing during this functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterations in gene and isoform expression, biochemical properties and morphological features that precipitate in modified contractile/mechanical characteristics. Insight into the molecular events that control these events was provided by the recent characterisation of the MyoD gene family, which encodes helix‐loop‐helix proteins; these activate muscle‐specific transcription and serve as targets for a variety of physiological stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contractile protein gene families, and (2) induce thyroid hormone receptor‐transcription factor interactions critical to gene expression. (shrink)

Development of gene transfer systems provides a key tool for understanding gene function. Exciting and often unexpected consequences from embryo manipulations are yielding insights into molecular mechanisms underlying development under normal and pathogenic states, and are providing animal models for diseases. Contributing to this progress is the elegant work on c‐fos(1), where Wagner and coworkers identify this proto‐oncogene as a primary factor which directs cell differentiation along the osteoclast/macrophage lineages, and thus regulates bone remodeling. Their studies support a (...) link between skeletogenesis, marrow formation and hematopoiesis, and may help to delineate mechanisms underlying the oncogenic transformation of skeletal and hematopoietic cells. (shrink)

A pianist’s movements are fundamental to music-making by producing the musical sounds and the expressive movements of the trunk and arms which communicate the music’s structural and emotional information making it valuable for this review to examine upper-body movement in the performance process in combination with the factors important in skill acquisition. The underpinning playing technique must be efficient with economic muscle use by using body segments according to their design and movement potential with the arm segments mechanically linked to (...) produce coordinated and fluent movement. Two physiologically and pianistically important actions proposed by early music scientists to deliver the keystroke involve dropping the hand from the shoulders towards the keys via a wave action with the joints activated sequentially, and forearm rotation to position the fingers for the keystroke, an action followed by the elbow/upper-arm rotating in the opposite direction. Both actions spare the forearm muscles by generating the energy needed in the larger shoulder muscles. The hand in the playing position has a curved palm through action of the metacarpal (knuckle) joints and curved fingers. Palm/finger posture controls sound quality from loud, high tempo sounds to a more mellow legato articulation, and to perform effectively the forearms should slope down towards the keyboard. The technique must be automatic through systematic practice which develops the motor skills for proficient playing, with practice duration tempered to reduce the risk of causing injury through overuse of the forearm muscles. Efficient movement patterns and strategic muscle relaxation which results in faster movement are realized only through extensive training. The constant movements of the head and trunk, and flowing arm movement with frequent hand lifts and rotational elbow movements, although generated in producing the playing technique, resonate with audience members who perceive them as expressive and thereby creating in them an empathic engagement with the music. It was proposed that music students be trained in the mechanical aspects of upper-body use in the playing technique, and practice strategies, with specialist pedagogy for children to develop motor skills for efficient playing, and training methods fostering an appreciation of the communicative aspects of music performance. (shrink)

What is the primary function of consciousness in the nervous system? The answer to this question remains enigmatic, not so much because of a lack of relevant data, but because of the lack of a conceptual framework with which to interpret the data. To this end, we have developed Passive Frame Theory, an internally coherent framework that, from an action-based perspective, synthesizes empirically supported hypotheses from diverse fields of investigation. The theory proposes that the primary function of consciousness is well-circumscribed, (...) serving the 'somatic nervous system[. For this system, consciousness serves as a frame that constrains and directs skeletal muscle output, thereby yielding adaptive behavior. The mechanism by which consciousness achieves this is more counterintuitive, passive, and “low level” than the kinds of functions that theorists have previously attributed to consciousness. Passive frame theory begins to illuminate (a) what consciousness contributes to nervous function, (b) how consciousness achieves this function, and (c) the neuroanatomical substrates of conscious processes. Our untraditional, action-based perspective focuses on olfaction instead of on vision and is 'descriptive' (describing the products of nature as they evolved to be) rather than 'normative' (construing processes in terms of how they should function). Passive frame theory begins to isolate the neuroanatomical, cognitive-mechanistic, and representational (e.g., conscious contents) processes associated with consciousness. (shrink)

My paper argues for the claim that religious experience may provide evidential reasons in support of religious beliefs. I name such a claim epistemic view of mystical experience (EM). In the first section, I sketch two approaches to EM. Swinburne, Alston and Plantinga (among others) develop a notable defense of EM. On the contrary, seminal works by Feuerbach and Bultmann offer the opposite account. I briefly show how to resist to the criticism of EM. In light of such line of (...) reasoning, I move to Alston's Theory of Doxastic Practices (TDP) in the second section. After giving a skeletal account of TDP, I construe an argument in Alstonian terms against the naturalist refutations of EM. In the third section, I highlight the main problem with TDP, that is, the claim that perceptions and religious experiences have an analogical relation. Examples from sacred texts of different traditions show that such a claim fails to grasp what a religious experience is. In the final section I give a preliminary account of the notion of presentational experience, and show that it is possible to defend EM more plausibly than TDP does by the use of this notion. (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints (...) act in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)

My purpose is to refute the intentionalist approach to perception. Drawing from mainstream literature, I identify a principle on which any version of intentional theory relies. My paper is a detailed attack on the truth of the principle. In the first section I will introduce terminology and will taxonomize various statements of the intentional view. In the second section I will briefly outline a sketch of the skeletal intentionalist theory that develops from the assumption of the principle alone. Then, (...) in the third section, I will advance my reasons against this theory. In the fourth section, I will set forth anintuitive and definitive counterexample to the adequacy of the principle of intentionalism to accounting for ordinary perception. Moving from this, in the fifth section, I will provide some reasons explaining why intentionalism is condemned at being unsuccessful. Finally, in the last section of the paper, I will give my conclusions. (shrink)

Mechanical stimulation has a critical role in the development and maintenance of the skeleton. This function requires the perception of extracellular stimuli as well as their conversion into intracellular biochemical responses. This process is called mechanotransduction and is mediated by a plethora of molecular events that regulate bone metabolism. Indeed, mechanoreceptors, such as integrins, G protein‐coupled receptors, receptor protein tyrosine kinases, and stretch‐activated Ca2+ channels, together with their downstream effectors coordinate the transmission of load‐induced signals to the nucleus and (...) the expression of bone‐related genes. During the past decade, scientists have gained increasing insight into the molecular networks implicated in bone mechanotransduction. In the present paper, we consider the major signaling cascades and transcription factors that control bone and cartilage mechanobiology and discuss the influence of the mechanical microenvironment on the determination of skeletal morphology. (shrink)

Public participation is well known for its practitioner insights and wealth of case reports. This knowledge is essential and has been well employed. Likewise, the theoretical literature on public participation is growing rapidly. The need for better conceptual and theoretical understandings of public participation has become clear. Public participation theories have not received great attention, and few have been proposed or tested. Yet theory offers much to practitioners of various interventions. The authors summarize work toward developing a public participation theory (...) and propose a way to conceptualize its skeletal components. The authors recognize that any theory must acknowledge that different people have different beliefs about what public participation should accomplish. Further, contextual variables affect a process’s character and outcomes. The authors begin with a discussion of theory’s importance to scholars, practitioners, and participants and provide an overview of existing approaches. The authors present findings from two empirical case studies used to further develop their theory of fair and competent public participation. They conclude with some observations about challenges and ways forward. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage (...) during the Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

This article explores the use of model organisms in studying the cognitive phenomenon of decision-making. Drawing on the framework of biological control to develop a skeletal conception of decision-making, we show that two core features of decision-making mechanisms can be identified by studying model organisms, such as E. coli, jellyfish, C. elegans, lamprey, and so on. First, decision mechanisms are distributed and heterarchically structured. Second, they depend heavily on chemical information processing, such as that involving neuromodulators. We end by (...) discussing the implications for studying distinctively human decision-making. (shrink)

Neurological diseases, particularly in the context of aging, have serious impacts on quality of life and can negatively affect bone health. The brain-bone axis is critically important for skeletal metabolism, sensory innervation, and endocrine cross-talk between these organs. This review discusses current evidence for the cellular and molecular mechanisms by which various neurological disease categories, including autoimmune, developmental, dementia-related, movement, neuromuscular, stroke, trauma, and psychological, impart changes in bone homeostasis and mass, as well as fracture risk. Likewise, how bone (...) may affect neurological function is discussed. Gaining a better understanding of brain-bone interactions, particularly in patients with underlying neurological disorders, may lead to development of novel therapies and discovery of shared risk factors, as well as highlight the need for broad, whole-health clinical approaches toward treatment. (shrink)

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation (...) of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration. (shrink)

I outline five issues in philosophy of colour that deserve greater attention and provide skeletal frameworks for how future work on these topics could be carried out. The issues are: colour and metaphilosophy, colour and artistic practice, colour and virtual/augmented reality, colour and imagination, and colour and the predictive mind. Some of these issues have been a focus of important recent works. Thus, colour conjoined with each of metaphilosophy, artistic practice and imagination have all been examined in at least (...) a few recent publications – see below for references. It is clear, however, that these recent works are signals that there is much still to be done. By contrast, while at present there is a great deal of interest in the predictive mind, the intersection of colour and the predictive mind is vastly underexplored. This is despite the fact that the philosophy and science of colour are rather developed disciplines. Finally, while there have been some very important recent works on virtual and augmented reality, the significance of colour for these studies has yet to be examined. It is my hope that after reading this article readers are convinced not only that the philosophy of colour has a rich, recent history, but also a very bright future. (shrink)

Hesyre was a high court official in ancient Egypt and lived about 2650 bc during the reign of King Djoser. He managed to combine religious as well as secular posts, and has the distinction of being the first recorded physician and firstknown dentist in history. Healthcare developed at an early period in ancient Egyptian history as is supported by the evidence from the skeletal and mummified remains, from the artistic record, as well as from inscriptional and textual sources. These (...) textual sources, the medical papyri, provide details of medical procedures undertaken, drugs employed and treatments provided - some of which have influenced modern medical practice. What we know about Hesyre comes from his impressive tomb at Saqqara, the walls of which are brightly decorated with items of daily life. Additionally, the tomb contained six fine wooden panels listing Hesyres titles, among them those relating to his practice of medicine and dentistry. (shrink)

Adenosine 5′-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term ‘purinergic’ was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. There (...) are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer. (shrink)

A two-stage procedure is described which induces type-logical grammar lexicons from sentences annotated with skeletal terms of the simply typed lambda calculus. First, a generalized formulae-as-types correspondence is exploited to obtain all the type-logical proofs of the sample sentences from their lambda terms. The resulting lexicons are then optimally unified. The first stage constitutes the semantic bootstrapping (Pinker, Language Learnability and Language Development, Harvard University Press, 1984), while the unification procedure of Buszkowski and Penn represents a first attempt (...) at structure-dependent distributional learning of the syntactic and semantic categories. This effort extends earlier induction procedures (Buszkowski and Penn, 1990, Studia Logica 49, 431–454; Kanazawa, 1998, CSLI Publications and the European Association for Logic, Language and Information) for classical categorial grammar to at first the non-associative Lambek calculus, and then to a large class of type logics enriched by modal operators and structural rules. (shrink)

A two-stage procedure is described which induces type-logical grammar lexicons from sentences annotated with skeletal terms of the simply typed lambda calculus. First, a generalized formulae-as-types correspondence is exploited to obtain all the type-logical proofs of the sample sentences from their lambda terms. The resulting lexicons are then optimally unified. The first stage constitutes the semantic bootstrapping (Pinker, Language Learnability and Language Development, Harvard University Press, 1984), while the unification procedure of Buszkowski and Penn represents a first attempt (...) at structure-dependent distributional learning of the syntactic and semantic categories. This effort extends earlier induction procedures (Buszkowski and Penn, 1990, Studia Logica 49, 431–454; Kanazawa, 1998, CSLI Publications and the European Association for Logic, Language and Information) for classical categorial grammar to at first the non-associative Lambek calculus, and then to a large class of type logics enriched by modal operators and structural rules. (shrink)

It is necessary to take into account the data of science in the theoretical debates conducted by scientists contributing ontological theories in order to develop new approaches to theological issues in Islamic thought. Even, Kalam scholars with the duty of defending and basing the principles of Islam in the classical sense have established a theological understanding intertwined with science in understanding both existence philosophically and the Script theologically. With its discoveries and theories in the last century, it can be argued (...) that modern science has made a serious progress compared to the past. Maintaining its own methodology and paradigm, every scientific discipline has the opportunity to benefit from the methods and data of other disciplines. Consequently, it is possible to assert that Kalam can enjoy the same opportunity too, as long as staying in its own problem area. According to modern science, the motion system is the unity of structures that enable living things to move. Moreover, Bones and joints, which are the structures of the skeletal system, are passive elements of the movement system. Muscles, on the other hand, are the active elements of the movement system and provide the movement of the body by affecting the bones and joints. Muscle tissue shapes the body by adhering to the bones, besides enabling movement activity to occur. One of the most important systems that provide movement is the nervous system. Because for a person to have movement, the muscles must contract, and the muscles must be stimulated for the contraction of the muscles. The system that enables this contraction to occur is the nervous system. Energy is also required for contraction to occur in the human body. Muscles create energy for movement by first providing their energy from the ATP molecule present in the muscle cells. Considering the movement theories of classical theology scholars, it is seen that they shaped the occurrence of human actions through the concept of potency. While the scholars classify power as spiritual/mental and physical strength in terms of its structure, they have characterized it as accident in terms of its nature. In this context, we can say that the equivalent of the power, which is regarded as necessary for the formation of human acts by the theologians, is the movement system in today's science. The spirit/mental that scholars regard as a structure of power for the occurrence of human action can be regarded as the electrical activity that activates muscles when considered within the framework of the movement system of today's science. It is seen that Kalam scholars emphasize physical competence in their definitions of power as well. At this point, Ash'arians defined the power as the soundness of organs, Mu’tazila expressed it as the presence of organs and their being away from disasters, and the Mâturîdîs stated it as the organs being healthy. With these definitions, Kalam scholars mean that a person should also be physically competent to make a movement. The structures scientifically accepted as biological and physical competence in the movement system are the skeletal system, muscles and nervous system. Therefore, we can say that the strength of the physical fitness/well-being emphasized in the definition of power by theologians corresponds scientifically to the skeletal system, muscles and nervous system. One of the issues that Kalam scholars discuss about power is the issue of the accident of power. The reason why they describe power as an accident is to emphasize its impermanence and to show that it was created by Allah. So, in modern science, electrical activity must occur in the brain in order for human organs to move. The occurrence of this electrical activity is independent of the human being. The fact that electrical activity occurs independently from human beings shows that it conforms to Kalam scholars’ definition of the accident. As a result, we can say that the theory of power created by scholars for human movement has a counterpart in the movement system put forward by today's science. (shrink)

The embryonic vertebrate face is composed of similarly sized buds of neural crest‐derived mesenchyme encased in epithelium. These buds or facial prominences grow and fuse together to give the postnatal morphology characteristic of each species. Here we review the role of neural crest cells and foregut endoderm in differentiating facial features. We relate the developing facial prominences to the skeletal structure of the face and review the signals and genes that have been shown to play an important role in (...) facial morphogenesis. We also examine two experiments one at the genetic level and one at the signal level in which transformation of facial prominences and subsequent change of jaw identity was induced. We propose that signals such as retinoids and BMPs and downstream transcription factors such as Distal‐less related genes specify jaw identity. BioEssays 25:554–568, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The Qur’an has been transmitted as both a written text and an oral recital. This has led to the development of a reading tradition that permits numerous different vocalisations to be made upon the basic skeletal text of the established ʿUthmānī codex. Ibn al-Jazarī chose ten early readers whom he felt were most representative of this tradition and whose readings are treated as canonical up until this day. One of these, the Kufan linguist al-Kisāʾī has been characterised in (...) the literature as more focused on the grammar of the Qur’an than his reader peers. This article explores al-Kisāʾī’s process of ikhtiyār when deciding between various possible readings. The sample for analysis consists of Kisāʾī’s tafarrudāt, the approximately fifty cases in which his reading differs from the other nine readers. By comparing his reading with the comments of early scholars of Qur’anic linguistics, especially his near-contemporary al-Farrāʾ, it is possible to construct a typology of the suspected principal reasons for al-Kisāʾī’s tafarrudāt. Not only are many of these based on grammatical preferences, but they demonstrate a significant degree of consistency. Furthermore, analysis of a cluster of readings with implications for the interpretation of the sharīʿa provides evidence for a subtle exegetical dimension to al-Kisāʾī’s work as a reader-grammarian. (shrink)

The “community effect” is necessary for tissue differentiation. In the Xenopus muscle paradigm, e‐FGF has been identified as a candidate community factor. Standley et al.1 now show that the community effect, mediated through FGF signalling, continues to be important at later stages of development in the posterior part of the embryo. In this region, the paraxial mesoderm is still undergoing segmentation into somites, which are the site of early skeletal muscle formation. Indeed, somitogenesis, together with the read‐out of (...) the Hox code, which confers anteroposterior positional identity, is regulated by FGF signalling. This raises the question of the co‐ordination between these events and the community effect which orchestrates myogenesis. BioEssays 25:13–16, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Broken Theory is a jettisoned collection of fragmentary writing, collected and collaged by new media artist, writer, musician, and theorist Alan Sondheim. Folding theoretical musings, text experiments, and personal confessions into a single textual flow, it examines the somatic foundations of philosophical theory and theorizing, discussing their relationships to the writer and body, and to the phenomenology of failure and fragility of philosophy's production. Writing remains writing, undercuts and corrects itself, is always superseded, always produced within an untoward and bespoke (...) silo - not as an inconceivable last word, but instead a broken contribution to philosophical thinking. The book is based on fragmentation and collapse, displacing annihilation and wandering towards a form of "roiling" within which the text teeters on the verge of disintegration. In other words, the writing develops momentary scaffoldings - writing shored up by the very mechanisms that threaten its disappearance. Broken Theory is prefaced by a text from Maria Damon and followed by an extensive interview with art historian Ryan Whyte. Alan Sondheim is a new media artist, theorist, and writer concerned with the phenomenology of the virtual. He has collaborated with motion capture and virtual environment labs. His work is concerned with the inhabitation of the body in the virtual; with the textuality of the body; with the problematic of mixed reality and codework. His writing is known for its "somatic grit" and skeletal codes that partially appear within and determine the surface. This style embeds interferences among syntax, semantics, and formal systems. The textual body, body of text and writer, are deeply entangled. His current work is based on the psychogeography of real and virtual worlds and their modeling. Most recently he has focused on "semantic ghosting" - the body behind the virtual/symbolic body - and modes of viral dispersion in a series of videos and texts. Sondheim was born in Wilkes-Barre, Pennsylvania, attended Brown University, and has exhibited, taught, and lectured at a number of venues in the United States and abroad. (shrink)

GraphicalExercise, neurotransmitters, growth factors, myokines, and potential effects on the brain.As human life expectancy increases, cognitive decline and memory impairment threaten independence and quality of life. Therefore, finding prevention and treatment strategies for memory impairment is an important health concern. Moreover, a better understanding of the mechanisms involved underlying memory preservation will enable the development of appropriate pharmaceuticals drugs for those who are activity limited. Exercise training as a non-pharmacological tool, has been known to increase the mean lifespan by (...) maintaining general body health and improving the cardiovascular and nervous systems function. Among different exercise training protocols, aerobic exercise has been reported to prevent the progression of memory decline, provided adequate exertion level, duration, and frequency. Mechanisms underlying exercise training effects on memory performance have not been understood yet. Convergent evidence suggest several direct and indirect mechanisms at molecular and supramolecular levels. The supramolecular level includes improvement in blood circulation, synaptic plasticity and neurogenesis which are under controls of complex molecular signaling of neurotransmitters, neurotrophic factors, exerkines, and epigenetics factors. Among these various factors, irisin/BDNF signaling seems to be one of the important mediators of crosstalk between contracted skeletal muscles and the brain during exercise training. This review provides an affordable and effective method to improve cognitive function in old ages, particularly those who are most vulnerable to neurodegenerative disorders. (shrink)

Low‐energy, pulsed electromagnetic fields (PEMFs) have reversed therapeutically resistant pathologic processes in the musculo‐skeletal system. Their development as a non‐thermal therapeutic agent is based on 30 years of study of the electro‐biological properties of connective tissues. Specific energy characteristics in applied PEMFs produce selected biological effects by modifying synthetic and other behavioral patterns of target cells; some mechanisms of action are defined. The technology appears safe and effective in clinical treatment of un‐united fractures, avascular necrosis of bone, and (...) chronic, refractory tendinitis. An expanding, rational use in biomedical science is predicted. (shrink)

The early evolutionary history of echinoderms was reconstructed on the basis of structural-functional considerations and application of the quasi-engineering approach of ‘Konstruktions-Morphologie’. According to the presented evolutionary scenario, a bilaterally symmetrical ancestor, such as an enteropneust-like organism, became gradually modified into a pentaradial echinoderm by passing through an intermediate pterobranch-like stage. The arms of a pentaradial echinoderm are identified as hydraulic outgrowths from the central coelomic cavity of the bilateral ancestor which developed due to a shortening of the body in (...) length but widening in the diameter. The resulting pentaradial symmetry is a consequence of mechanical laws that dictate minimal contact surface areas among hydraulic pneumatic entities. These developed in the coelomic cavity (metacoel) in the bilaterally symmetrical ancestor, when from the already U-shaped mesentery with the intestinal tract two additional U-shaped bows developed directly or subsequently. During the subsequent development tensile chords of the mesentery ‘sewed’ the gut with the body wall first in three and secondly in five ‘seams’. During the direct development five ‘seams’ between tensile chords and body wall developed straightly. These internal tensile chords subdivide the body coelom into five hydraulic subsystems (‘pneus’), which eventually arrange in a pentaradial pattern. The body could then enlarge only between the tensile chords, which means that five hydraulic bulges developed. These bulges initially supported the tentacles and finally each of them enclosed the tentacle until only the feather-like appendages of the tentacles projected over the surface. The tentacles with their feathers were transformedinto the ambulacral system, and the bulges become the arms. These morphological transformations were accompanied and partly determined by specific histological modifications, such as the development of mutable connective tissues and skeletal elements that fused to ossicles and provided shape stabilization in form of a calcareous skeleton in the body wall. The organism resulted was an ancestral echinoderm (‘Ur-Echinoderm’) with an enlarged metacoel, stabilized by hydraulic pressure working againsta capsule of mutable connective tissue, skeletal elements and longitudinal muscles. In regard to these reconstructions, the body structure of echinoderms can be understood as a hydraulic skeletal capsule. (shrink)

Both The Ferment of Knowledge and Geoffrey Cantor’s essay review defined the “eighteenth-century problem” in terms of the lack of a totalizing vision. Forty years on, the problem has shifted to the appropriation of eighteenth-century science by both the political left and the right. As historians grapple with the legacies of slavery and colonialism, an emerging theme is material culture and its “entanglements.” The subject of this essay, collections and collecting, is central to this new historiography. Collections included antiq­uities, natural (...) history, anatomy, and ethnographic objects. My focus will be on human skeletal collections. Historians who have considered skeletal collec­tions have focused mainly on the later eighteenth century and on developing concepts of race and geological time. But their significance is much broader. Collecting entailed entanglements both of cultures and of genres. Such collections could be medical, geological, aesthetic, taxonomic, or all or none of these. Case studies of collections of human bones, skeletons, and skulls reveal a different eighteenth century from that which the historians of 1980 envisaged, and bring questions of value and values to the centre of our reading of history. (shrink)

The myf5 and myoD genes are implicated in the specification of vertebrate skeletal muscle. These genes have been thought to be functionally redundant because neonatal mice bearing homozygous null mutations in either gene show grossly normal muscle development. By analyzing the early embryonic development of the mutants, Michael Rudnicki and coworkers show that trunk muscle development is retarded in embryos bearing myf5 null mutations, while early limb and branchial arch muscle development is retarded by myoD (...) null mutations.1 These results indicate that the myoD and myf5 genes are not redundant but that each controls the early specification of distinct muscle cell lineages. BioEssays 20:357–362, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Integrated developmental and elemental information in teeth provide a unique framework for documenting breastfeeding histories, physiological disruptions, and neurotoxicant exposure in humans and our primate relatives, including ancient hominins. Here we detail our method for detecting the consumption of mothers’ milk and exploring health history through the use of laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) mapping of sectioned nonhuman primate teeth. Calcium‐normalized barium and lead concentrations in tooth enamel and dentine may reflect milk and formula consumption with minimal modification during (...) subsequent tooth mineralization, particularly in dentine. However, skeletal resorption during severe illness, and bioavailable metals in nonmilk foods, can complicate interpretations of nursing behavior. We show that explorations of the patterning of multiple elements may aid in the distinction of these important etiologies. Targeted studies of skeletal chemistry, gastrointestinal maturation, and the dietary bioavailability of metals are needed to optimize these unique records of human health and behavior. (shrink)

Recent studies have yielded new insights into the critical importance of adequate vitamin D3 intake and metabolism. Investigations of the actions of 1,25‐dihydroxyvitamin D3 (calcitriol) on novel target tissues has revealed that this hormone has functions other than its recognized action in regulating blood calcium and phosphate levels. Reports have characterized calcitriol receptors and activities in organs and tissues as diverse as pancreas, skeletal and heart muscle, blood cells, brain, skin, pituitary, parathyroid, kidney, bone and intestine. These studies suggest (...) functions for calcitriol as varied as the regulation of insulin and prolactin secretion, muscle contractility, immune cell metabolism, melanin synthesis and differentiation of blood cells. This information may ultimately help us to understand the etiologies of several kinds of organ dysfunction and lead to the development of tissue‐specific agents for new therapies. (shrink)

The homologies of process within morphogenetic fields provide some of the best evidence for evolution—just as skeletal and organ homologies did earlier. Thus, the evidence for evolution is better than ever. The role of natural selection in evolution, how–ever, is seen to play less an important role. It is merely a filter for unsuccessful morphologies generated by development. Population genetics is destined to change if it is not to become as irrelevant to evolution as Newtonian mechanics is to (...) contempo–rary physics. (shrink)

The homologies of process within morphogenetic fields provide some of the best evidence for evolution—just as skeletal and organ homologies did earlier. Thus, the evidence for evolution is better than ever. The role of natural selection in evolution, however, is seen to play less an important role. It is merely a filter for unsuccessful morphologies generated by development. Population genetics is destined to change if it is not to become as irrelevant to evolution as Newtonian mechanics is to (...) contemporary physics. (Gilbert, Opitz, and Raff 1996, 368). (shrink)