How does conscious thought occur? In the scene 'The cat is next to the dog', the cat is within a proximal distance to the left or right of the dog. This probabilistic proximal left/right cognitive space is an example of a mental 'place field'. A place field -- also in humans presumably represented by place cells in the hippocampus -- represents latent and thus potentially unconscious thought. Mentally 'seeing' the cat to the left or right is an example of a (...) 'localized point' within a place field. A localized point represents manifest and thus conscious thought. As proposed, this field-to-point reduction is naturally described in terms of force dynamics, a prominent theory of causal cognition. Possible generalizations from spatial mental imagery to all conscious occurrences of thought and emotion are discussed. (shrink)

Mammalian outer hair cells generate mechanical forces at acoustic frequencies and can thus amplify the sound stimulus within the inner ear. The mechanism of force generation depends upon the plasma membrane potential but not upon either calcium or ATP. Forces are generated in the lateral cortex along the full length of the cell. The cortex includes a two‐dimensional cytoskeletal lattice composed of circumferential filaments 6–7 nm thick that are cross‐linked by filaments 3–4 nm thick and 40–60 nm (...) long. The two filament types may, respectively, be actin and some form of spectrin. The lattice reinforces the cylindrical shape of the cell and permits limited changes in length. Beneath it lie the lateral cisternae, a regular system of multi‐layered membranes. Force–generation may depend upon voltage‐dependent shape changes in proteins that lie either in the plasma membrane or in the cytoskeletal lattice. (shrink)

The cellular capacity to internalise objects, involving attachment, engulfment and uptake, exists in virtually all organisms. Many uptake reactions are associated with cell signalling. However, the mechanical forces that form endocytotic vesicles are not known. We propose a ‘leverage‐mediated’ uptake mechanism involving lateral cross‐linking processes on the cell surface that can generate the configurational energy to create an inverse curvature of the membrane. BioEssays 26:1344–1350, 2004. © 2004 Wiley Periodicals, Inc.

The YAP/TAZ family of transcriptional co‐activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB‐Hippo/MST‐Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal (...) signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST‐LATS or Src family kinase activity to modulate YAP/TAZ activity. (shrink)

Our human embryonic stem cell debates are not simply about good or bad ethical arguments. The fetus and the embryo have instead become symbols for a larger set of value conflicts occasioned by social and cultural changes. Beneath our stem cell debates lie conflicts between those who would privilege scientific progress and individual choice and others who favour the sanctity of family life and traditional family roles. Also at work, on both the national and international levels, is the (...) use of the embryo by newly emergent social groups to express resentment against cultural elites. The organisational needs of religious groups have also played a role, with the issue of protection of the embryo and fetus serving as a useful means of rallying organisational allegiance in the Roman Catholic and evangelical communities. Because the epiphenomenal moral positions on the status and use of the embryo are driven by the powerful social, cultural or economic forces beneath them, they will most likely change only with shifts in the underlying forces that sustain them. (shrink)

Imagine cells that live in a high‐gradient magnetic field (HGMF). Through what mechanisms do the cells sense a non‐uniform magnetic field and how such a field changes the cell fate? We show that magnetic forces generated by HGMFs can be comparable to intracellular forces and therefore may be capable of altering the functionality of an individual cell and tissues in unprecedented ways. We identify the cellular effectors of such fields and propose novel routes in cell (...) biology predicting new biological effects such as magnetic control of cell‐to‐cell communication and vesicle transport, magnetic control of intracellular ROS levels, magnetically induced differentiation of stem cells, magnetically assisted cell division, or prevention of cells from dividing. On the basis of experimental facts and theoretical modeling we reveal timescales of cellular responses to high‐gradient magnetic fields and suggest an explicit dependence of the cell response time on the magnitude of the magnetic field gradient. (shrink)

Traction forces developed by most cell types play a significant role in the spatial organisation of biological tissues. However, due to the complexity of cell-extracellular matrix interactions, these forces are quantitatively difficult to estimate without explicitly considering cell properties and extracellular mechanical matrix responses. Recent experimental devices elaborated for measuring cell traction on extracellular matrix use cell deposits on a piece of gel placed between one fixed and one moving holder. We formulate here (...) a mathematical model describing the dynamic behaviour of the cell-gel medium in such devices. This model is based on a mechanical force balance quantification of the gel visco-elastic response to the traction forces exerted by the diffusing cells. Thus, we theoretically analyzed and simulated the displacement of the free moving boundary of the system under various conditions for cells and gel concentrations. This modelis then used as the theoretical basis of an experimental device where endothelial cells are seeded on a rectangular biogel of fibrin cast between two floating holders, one fixed and the other linked to a force sensor. From a comparison of displacement of the gel moving boundary simulated by the model and the experimental data recorded from the moving holder displacement, the magnitude of the traction forces exerted by the endothelial cell on the fibrin gel was estimated for different experimental situations. Different analytical expressions for the cell traction term are proposed and the corresponding force quantifications are compared to the traction force measurements reported for various kind of cells with the use of similar or different experimental devices. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a (...) factor of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

The cell is not only the structural, physiological, and developmental unit of life, but also the reproductive one. So far, however, this aspect of the cell has received little attention from historians and philosophers of biology. I will argue that cell theory had far-reaching consequences for how biologists conceptualized the reproductive relationships between germs and adult organisms. Cell theory, as formulated by Theodor Schwann in 1839, implied that this relationship was a specific and lawful one, that (...) is, that germs of a certain kind, all else being equal, would produce adult organisms of the same kind, and vice versa. Questions of preformation and epigenesis took on a new meaning under this presupposition. The question then became one of whether cells could be considered as autonomous agents producing adult organisms of a given species, or whether they were the product of external, organizing forces and thus only a stage in the development of the whole organism. This question became an important issue for nineteenth-century biology. As I will demonstrate, it was the view of cells as autonomous agents which helped both Charles Darwin and Gregor Mendel to think of inheritance as a lawful process. (shrink)

Le présent article propose d’articuler la notion de bêtise telle qu’elle est élaborée par Gilles Deleuze dans ses premiers ouvrages au concept de honte. Dans cette articulation entre pensée philosophique, bêtise et honte, les théories cliniques déployées par Deleuze et Guattari s’imposent comme une élaboration centrale du projet métaphysique porté par Deleuze au travers du concept de bêtise. Le mouvement de pensée initié par Deleuze, prenant une ampleur explicitement clinique et politique avec Guattari, semble être réactivé dans le champ clinique (...) contemporain. Nous observons une actualité (ou une réactualisation) des critiques des théories psychanalytiques et psychiatriques qu’ils ont déployées dans les années 70. La figure deleuzienne de l’idiot permet de penser le type de position qu’occupent les auteurs et les autrices qui, actuellement, soulèvent les enjeux épistémologiques, politiques et cliniques du genre. Sur son revers, elle interroge ce que l’idiotie, au sens deleuzien, fait à la bêtise et à la honte. (shrink)

The cell is not only the structural, physiological, and developmental unit of life, but also the reproductive one. So far, however, this aspect of the cell has received little attention from historians and philosophers of biology. I will argue that cell theory had far-reaching consequences for how biologists conceptualized the reproductive relationships between germs and adult organisms. Cell theory, as formulated by Theodor Schwann in 1839, implied that this relationship was a specific and lawful one, that (...) is, that germs of a certain kind, all else being equal, would produce adult organisms of the same kind, and vice versa. Questions of preformation and epigenesis took on a new meaning under this presupposition. The question then became one of whether cells could be considered as autonomous agents producing adult organisms of a given species, or whether they were the product of external, organizing forces and thus only a stage in the development of the whole organism. This question became an important issue for nineteenth-century biology. As I will demonstrate, it was the view of cells as autonomous agents which helped both Charles Darwin and Gregor Mendel to think of inheritance as a lawful process. (shrink)

CELL AND PSYCHE THE BIOLOGY OF PURPOSE By EDMUND W. SINNOTT. PREFACE TO THE TORCHBOOK EDITION: SINCE the publication of this little book, as the McNair Lectures at the University of North Carolina, the author has written two others, as well as a number of papers, on the same gen eral theme. Though these elaborate the argument a little further, the essence of it is in Cell and Psyche. This is admittedly a specula tion, but one based solidly (...) on biological fact. It has been regarded as rather visionary and metaphysical by some people, but others have been attracted to it by the suggestion it offers for a better understanding of the ancient problem of how mind and body are related to each other. This problem is of such paramount impor tance, not only for a knowledge of what man really is but for the construction of a satisfying life philosophy, that any light thrown on it should be welcome. The suggestion that man's physical life grows out of the basic goal-seeking and purposiveness found in all organic behavior and that this, in turn, is an aspect of the more general self - regulating and normative character evident in the development and activities of living organisms, is at least worth serious consideration. If we are to avoid a dualistic idea of man's nature and to construct a true monism that does not require the sacrifice of the significance of either mind or body, some such conception as this seems a rea sonable means of doing so. It is to be hoped that the wider distri bution now made possible for the present book may result in a more general consideration of this particular relationship between biol ogy and philosophy* E. W. S. CONTENTS: Introduction. i I. Organization, the Distinctive Character of All Life 15 II. Biological Organization and Psychological Activity 43 IIL Some Implications for Philosophy 75 Suggested Readings. 112 Index. 117. INTRODUCTION: IN THE CLAMOR and confusion of our times one fact grows ever clearer beliefs are important. One of the major problems with which men now are faced per haps, indeed, the most important one is the wide dis agreement which still exists in their fundamental philos ophies. What course a man will follow, or a nation, is set in no small measure by his basic creed, by what he really thinks about the true nature of a human being his personality, his freedom, his destiny, his relations to others and to the rest of the universe; by the judgments lie makes as to what qualities and courses of action are admirable and should command his allegiance. These are not academic questions merely. They arc ancient mys teries which long have troubled human hearts and seem today almost as far as ever from solution. The answer a ny* n gives to them is the most significant thing that one can know about him. We may be tempted to under estimate the importance of these inner directives and turn instead to outer influences, to economic and social factors, as more decisive for our actions. But when we look at what the philosophy of Marx has done to set one half the world against the other, at the basic divergence between the thinking of East and West, and at so many other differences in political and religious beliefs which now divide mankind, we can hardly doubt the profound practical import of men's philosophies. It is still true today that as a man thinketh in his heart, so is he. In the minds of men are the most fateful battles fought. Against those ideologies we condemn, force in the end will fail. If our opponents cannot be convinced, or their ideas reconci. (shrink)

The closely related debates concerning abortion, the protection of the embryo and stem cell science have captured the legislative agenda in Mexico in recent years. This paper examines some contemporary debates related to stem cell science and the legal and political action that has followed in the wake of the latest Supreme Court judgment on abortion, which debates are directly linked to the degrees of protection of the embryo stipulated in the Mexican Constitution. While some Mexican states have (...) opted to take no further action, others, where conservative political forces are in the majority, have been very active in seeking to ensure that their constitutions are amended to protect human life from conception onwards. This intense legislative activity has not, however, been repeated at the federal level, where there is currently no overarching national regulatory framework governing stem cell research. Although major efforts have been made by the conservative block within the Senate to bring forward legislative proposals for the prohibition of human embryonic stem cell research, and despite the public expression by the federal government of its commitment to encourage inward investment and innovation in the area of biotechnology, stem cell science has, so far, remained unregulated. The legislative challenge is to resist the pressure that has been injected by religious leaders and to act in accordance with the values and principles adopted by the community in the Mexican Constitution. In the final analysis, Mexico faces particular difficulties in accommodating conservative political forces on one hand, while recognising on the other its need, as an emerging economy, to promote a progressive approach to innovation in biotechnology. (shrink)

Physical forces regulate numerous biological processes during development, physiology, and pathology. Forces between the external environment and intracellular actin cytoskeleton are primarily transmitted through integrin‐containing focal adhesions and cadherin‐containing adherens junctions. Crosstalk between these complexes is well established and modulates the mechanical landscape of the cell. However, integrins and cadherins constitute large families of adhesion receptors and form multiple complexes by interacting with different ligands, adaptor proteins, and cytoskeletal filaments. Recent findings indicate that integrin‐containing hemidesmosomes oppose force (...) transduction and traction force generation by focal adhesions. The cytolinker plectin mediates this crosstalk by coupling intermediate filaments to the actin cytoskeleton. Similarly, cadherins in desmosomes might modulate force generation by adherens junctions. Moreover, mechanotransduction can be influenced by podosomes, clathrin lattices, and tetraspanin‐enriched microdomains. This review discusses mechanotransduction by multiple integrin‐ and cadherin‐based cell adhesion complexes, which together with the associated cytoskeleton form an integrated network that allows cells to sense, process, and respond to their physical environment. (shrink)

According to vitalism, living organisms differ from machines and all other inanimate objects by being endowed with an indwelling immaterial directive agency, ‘vital force,’ or entelechy . While support for vitalism fell away in the late nineteenth century many biologists in the early twentieth century embraced a non vitalist philosophy variously termed organicism/holism/emergentism which aimed at replacing the actions of an immaterial spirit with what was seen as an equivalent but perfectly natural agency—the emergent autonomous activity of the whole organism. (...) Organicists hold that organisms unlike machines are ‘more than the sum of their parts’ and predict that the vital properties of living things can never be explained in terms of mechanical analogies and that the reductionist agenda is doomed to failure. Here we review the current status of the mechanist and organicist conceptions of life particularly as they apply to the cell. We argue that despite the advances in biological knowledge over the past six decades since the molecular biological revolution, especially in the fields of genetics and cell biology the unique properties of living cells have still not been simulated in mechanical systems nor yielded to reductionist—analytical explanations. And we conclude that despite the dominance of the mechanistic–reductionist paradigm through most of the past century the possibility of a twentyfirst century organicist revival cannot be easily discounted. (shrink)

Although analogical reasoning has long been a popular method of reasoning in bioethics, current literature does not sufficiently grasp its variety. We assert that the main shortcoming is the fact that an analogy's value is often judged on the extent of similarity between the source situation and the target situation, while in (bio)ethics, analogies are often used because of certain dissimilarities rather than in spite of them. We make a clear distinction between dissimilarities that aim to reinforce a similar approach (...) in the source situation and the target situation and dissimilarities that aim to undermine or denounce a similar approach. The former kind of dissimilarity offers the analogy more normative force than if there were no dissimilarities present; this is often overlooked by authors who regard all relevant dissimilarities as detrimental to the analogy's strength. Another observation is that an evaluation of the normative force of an analogy cannot be made independently of moral principles or theories. Without these, one cannot select which elements in an analogy are morally relevant nor determine how they should be interpreted. (shrink)

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. (...) We propose here an evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Significant strides have been made in recent years towards understanding the molecular basis of cell cycle progression in the model bacterium Caulobacter crescentus. At the heart of cell cycle regulation is a multicomponent transcriptional feedback loop, governing the production of successive regulatory waves or pulses of at least three master regulatory proteins. These oscillating master regulators direct the execution of phase‐specific events and, importantly, through intrinsic genetic switches not only determine the length of a given phase, but also (...) provide the driving force that catapults the cell into the next stage of the cell cycle. The genetic switches act as fail safe mechanisms that prevent the cell cycle from relapsing and thus govern the ordered production and the periodicity of these regulatory waves. Here, we detail how the master regulators CtrA, GcrA and DnaA coordinate cell cycle progression and polar development in Caulobacter. BioEssays 28: 355–361, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The position of the spindle determines the position of the cleavage plane, and is thus crucial for cell division. Although spindle positioning has been extensively studied, the underlying forces ultimately responsible for moving the spindle remain poorly understood. A recent pioneering study by Garzon‐Coral et al. uses magnetic tweezers to perform the first direct measurements of the forces involved in positioning the mitotic spindle. Combining this with molecular perturbations and geometrical effects, they use their data to argue (...) that the forces that keep the spindle in its proper position for cell division arise from astral microtubules growing and pushing against the cell's cortex. Here, we review these ground‐breaking experiments, the various biomechanical models for spindle positioning that they seek to differentiate, and discuss new questions raised by these measurements. (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)

Beta‐oxidation of fatty acids and detoxification of reactive oxygen species are generally accepted as being fundamental functions of peroxisomes. Additionally, these pathways might have been the driving force favoring the selection of this compartment during eukaryotic evolution. Here we performed phylogenetic analyses of enzymes involved in beta‐oxidation of fatty acids in Bacteria, Eukaryota, and Archaea. These imply an alpha‐proteobacterial origin for three out of four enzymes. By integrating the enzymes' history into the contrasting models on the origin of eukaryotic cells, (...) we conclude that peroxisomes most likely evolved non‐symbiotically and subsequent to the acquisition of mitochondria in an archaeal host cell. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 97-114 [Access article in PDF] Stem Cell Research in the U.S. after the President's Speech of August 2001 Cynthia B. Cohen On 9 August 2001, in a nationally televised speech, President Bush addressed the contentious question of whether to provide federal funds for human embryonic stem cell research (White House 2001).1 This research involves taking the primordial cells found in (...) embryos and transforming them into certain specialized cells, such as those of the heart, nerves, and muscles, with the ultimate goal of transferring these cells into patients to repair damaged cells and tissues. In his remarks, the President authorized funding for research only on stem cells already harvested from remaining embryos at in vitro fertilization (IVF) centers as of 9 August 2001, the date of the speech. In a "Fact Sheet" about embryonic stem cell research, he added the ethical requirements that (1) the donors of embryos gave informed consent to the derivation of stem cells from their embryos, (2) the embryos were created solely for reproductive purposes, and (3) no financial inducements were given to the embryo donors. The President also prohibited federally funded research on embryonic stem cells derived from embryos after 9 August 2001, as well as the creation of embryos for research purposes and the cloning of human embryos for both reproductive and research purposes. He did not seek to ban the pursuit of embryonic stem cell research with private funds. "This allows us to explore the promise and potential of stem-cell research without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of embryos," the President stated (White House 2001).The President's speech stirred intense controversy. Many applauded the new policy because it allowed some embryonic stem cell research to proceed, thereby raising hope that treatments might be developed for those suffering from such conditions as Parkinson's disease, Alzheimer's disease, and diabetes. Others supported it on grounds that it would discourage the future destruction of embryos in stem cell research. They maintained that although it was wrong to have derived stem cells from embryos, this wrong was no longer remediable and it therefore was justifiable to allow research using such embryos to proceed. Some, however, objected to the new policy because they held that it unduly limited the [End Page 97] number of embryonic stem cells available for federally funded research. Still others opposed it on grounds that it made the federal government complicit in what they took to be the wrongful destruction of human embryos that had taken place prior to 9 August 2001. The President established the President's Council on Bioethics by executive order in November 2001 and charged it, among other tasks, with monitoring stem cell research and recommending guidelines and regulations for biomedical innovations.Questions about the moral status of human embryos have so captured public attention since the President issued his remarks that other significant ethical and policy issues raised about stem cell research inside the Beltway have remained in the shadows. A number of individuals and organizations—legislators, scientists, patient groups, the President's Council on Bioethics, ethicists, religious task forces, and social commentators—have attempted to bring these other issues to legislative and public attention. They also have revisited the more publicly prominent question of what sorts of protections we owe to human embryos. In response, Congress has attempted to address several of these newly emerging issues at hearings and in legislation. I review these efforts, consider developing issues and arguments, and conclude by exploring possible future directions for federal and private sector stem cell policy. The Availability of Embryonic Stem Cell Lines to Federally Funded Researchers President Bush, in developing his stem cell research policy, accepted a distinction between the "derivation" and the "use" of embryos enunciated by the General Counsel of the Department of Health and Human Services toward the end of the Clinton administration. This distinction was adopted to avoid contravening the Dickey-Wicker Amendment (added... (shrink)

Où trouver la force de continuer à vivre quand des épreuves terribles privent de l'énergie ou du désir nécessaires pour perpétuer une existence devenue en apparence absurde? Les récits de résilience sont nombreux. Mais il aura fallu attendre Nietzsche pour que la philosophie s'empare avec acuité de cette question. ± [...] je fis de ma volonté de santé, de vivre, ma philosophie? : accablé d'une maladie terriblement douloureuse, l'auteur du Gai Savoir fait d'une expérience vécue un terrain d'expérimentation pour la (...) pensée. La force de vivre est exclusive chez lui de toute recherche d'un quelconque salut dans une foi ou dans une cause. Non pas fuir la maladie, mais se l'approprier en l'explorant par la pensée. En découlent une leçon et une question. Une leçon : la souffrance ne prive pas la vie de son sens, ni ne préjuge de sa valeur. Une question, celle du philosophe qui se fait ± médecin de la civilisation? : le nihilisme peut-il être surmonté? (shrink)

Appartient-il au philosophe de fixer strictement la compréhension de notre concept d'art, ou doit-il limiter sa tâche à celle d'une clarification de ses usages? À cette question, les textes de Jean-Pierre Cometti réunis dans ce volume répondent en choisissant la voie d'une esthétique « minimale », qui renonce aux vertiges de l'ontologie et aux ambitions définitionnelle de la philosophie analytique de l'art, tout en prenant acte du caractère caduc des grands récits spéculatifs hérités de l'esthétique idéaliste ou des mirages de (...) la déconstruction. (shrink)

An important question for bacterial cell division is how the invaginating septum can overcome the turgor force generated by the high osmolarity of the cytoplasm. I suggest that it may not need to. Several studies in Gram‐negative bacteria have shown that the periplasm is isoosmolar with the cytoplasm. Indirect evidence suggests that this is also true for Gram‐positive bacteria. In this case the invagination of the septum takes place within the uniformly high osmotic pressure environment, and does not have (...) to fight turgor pressure. A related question is how the V‐shaped constriction of Gram‐negative bacteria relates to the plate‐like septum of Gram‐positive bacteria. I collected evidence that Gram‐negative bacteria have a latent capability of forming plate‐like septa, and present a model in which septal division is the basic mechanism in both Gram‐positive and Gram‐negative bacteria. (shrink)

Résumé L’immortalité est la grande quête de l’humanité, l’utopie par excellence. René Barjavel, dans son roman de science fiction Le grand secret, pense la convergence entre l’amour qui défie le temps, la science qui vient à bout de la maladie et la sagesse qui triomphe de la mort. Spinoza nous rappelle que la mort ne peut pas avoir ontologiquement une place dans la pensée des vivants et Bergson suppose un « courant de vie » traversant les corps et les générations, (...) se divisant et s’intensifiant sans perdre de force. Cette force de vivre n’a rien à voir avec les nouvelles philosophies du trans-humain ou du post-humain qui s’imaginent une post-humanité vivant plus longtemps, en meilleure santé et moins malheureuse, grâce à la biotechnologie. Si l’humanité a représenté dans la ligne de l’évolution une ouverture exceptionnelle, celle-ci est intensification, création et émancipation et non pas extension et rajout comme le veulent les sciences de la vie. (shrink)

Shape and locomotion of tissue cells depend on the interaction of elements of the cytoskeleton, adhesion to the substrate and an intracellular hydrostatic pressure. The existence of this pressure becomes obvious from increase in cell volume on cessation of contractile forces and from observations with ultrasound acoustic microscopy. Wherever such an internal pressure is established, it is involved in generation of shape and driving force of cell locomotion. Therefore each hypothesis on cell shape and locomotion must (...) consider this property of a living cell. Apparently different types of locomotion depend on differences in substrate adhesion and/or cytoskeleton organisation. (shrink)

The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. (...) Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives. (shrink)

Somatic cell nuclear transfer (SCNT) remains a controversial technique, one that has elicited a variety of regulatory responses throughout the world. On March 29, 2005, Canada's Assisted Human Reproduction Act came into force. This law prohibits a number of research activities, including SCNT. Given the pluralistic nature of Canadian society, the creation of this law stands as an interesting case study of the policy-making process and how and why a liberal democracy ends up making the relatively rare decision to (...) use a statutory prohibition, backed by severe penalties, to stop a particular scientific activity. In this article, we provide a comprehensive and systematic legal analysis of the legislative process and parliamentary debates associated with the passage of this law. (shrink)

The chromosomes which segregate in anaphase I of meiosis are usually physically bound together through chiasmata. This association is necessary for proper segregation, since univalents sort independently from one another in the first meiotic division and this frequently leads to genetically unbalanced offspring. There are, however, a number of species where genetic exchanges in the form of meiotic cross‐overs, the prerequisite of the formation of chiasmata, are routinely missing in one sex or between specific chromosomes. These species nevertheless manage to (...) segregate these non‐exchange chromosomes. There are four direct modes for associating achiasmatic chromosomes: (a) modified SC, (b) adhesion of chromatids comparable to somatic pairing, (c) ‘stickiness’ of heterochromatin or (d) specific ‘segregation bodies’, consisting of material structurally different from chromatin. There is also the possibility that the spindlepossibly joining forces with the kinetochores‐carries out the faithful segregation of univalents which are not directly physically attached to one another. Finally, amphitelic orientation of univalents in metaphase I and pairing of the chromatids in meiosis II appear to ensure correct segregation as well. (shrink)

Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease, a transmissible cancer, afflicting Tasmanian devils, provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts. Here we provide an overview of (...) parasite-induced host life history adaptations, then both phenotypic plasticity of LH responses and changes in allele frequencies that affect LH traits of Tasmanian devils in response to DFTD are discussed. We conclude that akin to parasites, cancer can directly and indirectly affect devil LH traits and trigger host evolutionary responses. Consequently, it is important to consider oncogenic processes as a selective force in wildlife. Exposure to transmissible cancer cells, i.e., Tasmanian devil facial tumour cells, can cause changes to life history traits either as the result of phenotypic plasticity in response to exposure during the lifetime of the individual or as the result of evolutionary change in LH traits due to selection over generations.Photo credits: Frédéric Thomas, Sarah Peck, Geordie Jennings. (shrink)

The affinities of antibodies (Abs) for their target antigens (Ags) gradually increase in vivo following an infection or vaccination, but reach saturation at values well below those realisable in vitro. This ‘affinity ceiling’ could in many cases restrict our ability to fight infections and compromise vaccines. What determines the affinity ceiling has been an unresolved question for decades. Here, we argue that it arises from the strength of the chain of protein complexes that is pulled by B cells during the (...) process of Ag acquisition. The affinity ceiling is determined by the strength of the weakest link in the chain. We identify the weakest link and show that the resulting affinity ceiling can explain the Ab affinities realized in vivo, providing a conceptual understanding of Ab affinity maturation. We explore plausible evolutionary underpinnings of the affinity ceiling, examine supporting evidence and alternative hypotheses and discuss implications for vaccination strategies. (shrink)

La force créatrice du discours que décrit Taylor permet-elle aux subordonnés de parler en leur nom propre? Pour répondre à cette question, j’emprunte au concept de politique de Jacques Rancière. J’affirme que la distinction de Taylor entre HLC et HHH ressemble à celle qu’établit Rancière entre «politique» et «police». Toutefois, parce que la force créatrice du discours réitère l’ordre humain, elle n’est pas politique en elle-même. J’aborde l’exemple de la relation «avunculaire» présenté par de Taylor pour illustrer à quel moment (...) la force créatrice peut s’avérer, ou non, un fondement de la politique. (shrink)

Stem cell tourism—the flow of patients from home countries to destination countries to obtain stem cell treatment—is a growing business in China. Many concerns have been raised regarding fraudsters that operate unsafe stem cell therapies and an officialdom that turns a blind eye to the questionable technology. The Chinese regulatory approach to stem cell research is based on Guidelines and Administrative Measures, rather than legislation, and may have no binding force on certain institutions, such as military (...) hospitals. There is no liability and traceability system and no visible set of penalties for non-compliance in the stem cell legal framework. In addition to the lack of safety and efficacy systems in the regulations, no specific expert authority has been established to monitor stem cell therapy to date. Recognizing the global nature of stem cell tourism, this article argues that resolving stem cell tourism issues may require not only the Chinese government but also an international mechanism for transparency and ethical oversight. A stringent set of international regulations that govern stem cell therapies can encourage China to improve stem cell regulation and enforcement to fulfill its obligations. Through an international consensus, a minimum standard for clinical stem cell research and a central enforcement system will be provided. As a result, rogue clinics that conduct unauthorized stem cell therapies can be penalized, and countries that are reluctant to implement the reconciled regulations should be sanctioned. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Future Directions for Oversight of Stem Cell Research in the United States: An UpdateMary A. Majumder (bio) and Cynthia B. Cohen (bio)On 9 March 2009, President Barack Obama (2009a) signed an executive order revoking the statement issued by President George W. Bush during a televised speech in August 2001, in which the latter had sharply restricted the scope of federally funded human embryonic stem cell (hESC) research (...) to cell lines derived (without federal funding) prior to 9:00 P.M. EDT on 9 August 2001. Action by President Obama to remove the cut-off date had been expected. It came as a surprise, however, that he gave authority to determine the scope of eligible research to the Director of the National Institutes of Health (NIH), referencing only general concerns of responsibility, scientific worth, and legality.1 This contrasted not only with the approach of former President Bush, but also with that of former President Clinton, who had expressed personal opposition to the creation of embryos for research and had a distinction between hESCs derived from embryos created for research and those derived from spare embryos enshrined in NIH policy.President Obama’s remarks upon signing the executive order give some insight into the thinking behind his approach. Implicit in them are the views that earlystage human embryos outside the womb do not have full moral status and that the destruction of human embryos in the effort to care for and ease the suffering of human beings who do have full moral status does not devalue human life. The President also stressed that the decision to pursue hESC research reflected not only his opinion, but also a broad social consensus. He concluded with strong ethical commitments on two fronts:We will develop strict guidelines, which we will rigorously enforce, because we cannot ever tolerate misuse or abuse. And we will ensure that our government never opens the door to the use of cloning for human reproduction. It is dangerous, profoundly wrong, and has no place in our society, or any society.(Obama 2009b)The specific guarantee that President Obama gave against government support for the development of cloning techniques for human reproductive purposes made his silence on the use of cloning for research seem significant. Comments he had made in the course of the campaign (Obama 2008) suggested that he would affirm [End Page 195] the Clinton-era policy of limiting federal funding to hESCs derived from spare embryos. Did this silence mean that President Obama was opening the door to federal funding of research cloning when and if scientists might manage that feat?2009 NIH GuidelinesThe answer to this question and several others came on 17 April, when Raynard Kington, the acting director of NIH, released Draft NIH Guidelines for Human Stem Cell Research (NIH 2009), developed by an NIH Stem Cell Task Force, along with a request for public comment within 30 days of their publication in the Federal Register.2 The 2009 Draft Guidelines exclude from federal funding the derivation of hESCs, a restriction mandated by the reenactment of the Dickey-Wicker Amendment as part of the 2009 Omnibus Appropriations Act (Public Law 111-8, Division F, Title V, § 509). The 2009 Draft Guidelines also exclude the use of hESCs derived from embryos created for research purposes, and so represent a refusal to open the funding door as broadly as the NIH interpretation of the Dickey-Wicker Amendment might allow, at least for the time being.It appears that the drafters used as their starting point the 2000 NIH Guidelines for Research Using Human Pluripotent Stem Cells (NIH 2000) dating from the Clinton Administration, rather than more recent guidelines from the National Academy of Sciences (National Research Council 2005; 2007; 2008) and other private bodies. Both the format and content of the 2000 and 2009 NIH efforts are similar, making the departures in the latter stand out in high relief. We highlight departures related to informed consent to embryo donation, creation of human-nonhuman chimeras, and the role of an NIH task force, updating our original comment (Cohen and Majumder 2009).Informed Consent to Embryo DonationThe 2009 NIH Draft Guidelines require that certain statements... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Future Directions for Oversight of Stem Cell Research in the United StatesCynthia B. Cohen (bio) and Mary A. Majumder (bio)Human pluripotent stem cell research, meaning research into cells that can multiply indefinitely and differentiate into almost all the cells of the body, has become a minefield in which science, ethics, and politics have collided over the last decade in the United States. President Barack Obama entered this (...) highly charged territory when he indicated during his campaign that once in office he would issue an executive order expanding federally funded human embryonic stem cell (hESC) research and introduce rigorous oversight of it (Obama 2008a & b). Candidate Obama stated that he would require that the hESC lines involved were derived with donor consent from early embryos that otherwise would be discarded following in vitro fertilization (IVF) treatment. However, in contrast with the policy of President George W. Bush, he would do so without regard to the date of their derivation. He added that he would call upon the director of the National Institutes of Health (NIH) to develop guidelines for federally funded hESC and other pluripotent stem cell research that would draw from the guidelines developed in 2005 by the National Academies of Science (NAS) for privately funded research (National Research Council 2005).A similar policy was written into the 2008 version of the Stem Cell Research Enhancement Act, which reiterates the policy enunciated in earlier versions of this bill, passed twice by the Congress but vetoed by President Bush each time (House of Representatives, 110th Congress 2008).1 Depending on how one reads the 2008 version of the act, it could also apply in certain respects to hESC research that is not federally funded. We proceed on the assumption that the act applies at least to federally funded stem cell research. Therefore, it appears that the president or the Congress, or both, will approve of an expanded policy of federal funding of hESC research, as well as other forms of human pluripotent stem cell research. [End Page 79]This policy would make the guidelines developed by a committee appointed by NAS, a prestigious private body of American scientists and related experts, the primary basis for the development of new federal guidelines for oversight of hESC research in the United States. This would have certain advantages in that those familiar with the relevant scientific issues are likely to address them accurately and stem cell investigators are apt to accept restrictions on their research written by fellow scientists and ethics and policy experts whom they perceive as strong supporters of stem cell research. However, it also would have certain disadvantages. Chief among these is that the NAS committee appointed to write guidelines for this research, in its concern to see stem cell science move forward after a period in which many scientists and others maintained that it had been unduly restricted, might have overlooked or deferred consideration of some pressing ethical and policy issues. We maintain that this is the case—although we also maintain that the NAS guidelines provide a responsible foundation for developing NIH guidelines for stem cell research. Consequently, we propose that an NIH task force charged by the director of NIH with writing new guidelines for hESC and other stem cell research should revise and expand the NAS guidelines in ways that we propose below, as well as others that it considers necessary, and make it obligatory for those seeking federal funding of such research to follow these new guidelines.We highlight certain areas in which an ethical case can be made for strengthening the existing NAS guidelines and certain areas in which more fundamental ethical reflection—and building on that, additional guideline/policy development—seems warranted. Among the sections of the NAS guidelines that need clarification and reworking, we include those regarding consent to embryo donation, which provide one of their central focuses, and the development of human-nonhuman chimeras, which they address relatively briefly. In addition, we maintain that new guidelines need to be written to address the nascent ethical and policy issues raised by the possibility that human gametes will be induced from pluripotent stem cells in the next few years and that... (shrink)

Il s’agira ici de faire apparaître la régressivité — possibilité perpétuelle d’adjoindre un degré supplémentaire à l’énoncé — comme le principe même de l’ironie, ce qui conduit à la concevoir non comme une grille sémiotique et axiologique, mais comme une dynamique.La réflexion part de la cellule de base qu’est le signe ironique en tant que structure hiérarchisée à deux degrés, selon la conception traditionnelle. Cette dualité est d’abord analysée du point de vue sémantique, dans le cadre tropologique, puis sur les (...) plans axiologique, actantiel et énonciatif, ce qui aboutit à l’hypothèse de l’ironie comme trope métadiscursif, cumulant l’usage et la mention . Dans ce cadre, l’ironie se conçoit comme une représentation de représentation, comme un processus d’auto-duplication agissant par réflexivité critique et comique, et donc capable de se perpétuer virtuellement à l’infini puisque, s’appliquant à lui-même, il peut toujours ajouter un degré au précédent, sans pour autant l’annuler : le signe à deux niveaux ne constitue que la réalisation minimale de l’ironie, dont le second degré peut lui-même être réfléchi par un troisième, etc. Le « pouvoir réfléchissant » de l’ironie fait ainsi sa « force ascensionnelle » régressive, selon deux expressions empruntées à Proust.Interne au signe, ce dynamisme permet aussi, à l’échelle d’une oeuvre, de greffer différentes sortes d’ironie les unes sur les autres : la puissance créatrice du processus régressif conduit à envisager son rôle dans l’oeuvre d’art, en l’occurrence À la recherche du temps perdu, dont le texte multiplie de façon exemplaire et retorse les strates d’ironie. La Recherche, qui aura préalablement servi de support à toutes les analyses, permettra, par l’intermédiaire de Bergotte — écrivain ironiste dont le génie consiste dans le « pouvoir réfléchissant » et l’énergie créatrice dans la « force ascensionnelle » —, de poser la question de l’actualisation de la régressivité ironique dans l’oeuvre littéraire.Regressivity, as the perpetual possibility of adding a further degree to an utterance is the very principle of irony, which is thus conceived not under a semiotic and axiological grid, but as a dynamics.Reflection starts from the ironic sign as the basic cell and as a two tiered hierarchical structure, according to the traditional conception. This duality is first analysed from a semantical point of view, within the tropological framework, then on the axiological, actancial and utterance theoretic levels. This leads us to the hypothesis that irony is a metadiscursive trope, bringing together use and mention . Within this framework, irony is a representation of representation, an auto-duplicative process which acts through critical and comical reflectivity, and which is liable to perpetuate itself indefinitely, since, being auto-applicative, a new degree can always be added to the previous one, without cancelling itself : the two tiered sign being only the minimal realisation of irony, whose second degree can itself be reflected through a third, and so on. The “reflective power” of irony thus produces its “ascending force”.This mechanism internal to the sign allows also, at the level of the work, to plug different kinds of ironies onto each other : the creative power of the regressive process allows us to envisage its role in the work of art, in the case at hand in Remembrance of Things Past, whose text multiplies the various layers of irony. Proust’s work, which is here the basis of all our analyses, allows Bergotte — the ironist writer whose genius consists in the “reflective power” and in the “ascending force” — to raise the question of the actualisation of the ironical regressivity of the literary work. (shrink)

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that mutations in their members are causative (...) of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity.Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues. (shrink)

Actomyosin (actin‐myosin II complex)‐mediated contractile forces are central to the generation of multifaceted uni‐ and multi‐cellular material properties and dynamics such as cell division, migration, and tissue morphogenesis. In the present article, we summarize our recent researches addressing molecular mechanisms that ensure actomyosin‐mediated directional cell–cell junction remodeling, either shortening or extension, driving cell rearrangement for epithelial morphogenesis. Genetic perturbation clarified two points concerning cell–cell junction remodeling: an inhibitory mechanism against negative feedback in which (...) actomyosin contractile forces, which are well known to induce cell–cell junction shortening, can concomitantly alter actin dynamics, oppositely leading to perturbation of the shortening; and tricellular junctions as a point that organizes extension of new cell–cell junctions after shortening. These findings highlight the notion that cells develop underpinning mechanisms to transform the multi‐tasking property of actomyosin contractile forces into specific and proper cellular dynamics in space and time. (shrink)

With historical hindsight, it can be little questioned that the view of protozoa as unicellular organisms was important for the development of the discipline of protozoology. In the early years of this century, the assumption of unicellularity provided a sound justification for the study of protists: it linked them to the metazoa and supported the claim that the study of these “simple” unicellular organisms could shed light on the organization of the metazoan cell. This prospect was significant, given the (...) state of cytology circa 1910. In the wake of the major gains made in understanding nuclear division in the last two decades of the nineteenth century, cytology was suddenly confronted with many, seemingly less penetrable, problems. Several aspects of nuclear organization still remained unexplained, and recent research had revealed the presence in the cytoplasm of structures whose functions in cell life were unknown. Classical methods of cytology, relying on descriptive, morphological analysis, seemed ill equipped to resolve these questions.Hertwig's program for protozoology, grounded in the assumption of the fundamental unity of organization in protozoa and metazoa, offered a potential means for investigating these and other problems of cell theory. Linked to mainstream cytology, protozoology was advocated as a means of experimentally investigating key biolobical processes — reproduction, metabolism, and organelle morphology and physiology — less accessible in higher organisms. Protozoa were hailed as prime experimental organisms, in which cell structure and function could be more easily studied. Unlike the metazoan cell, they could be subjected to controlled experiments in which the external environment was modified and the effects monitored. Protozoa offered, in other words, a promising experimental means by which to investigate the cell — its structures and its processes.The success of this program within Germany was soon apparent. In contrast to the rather neglected state of the discipline in 1900, protozoology began to be recognized as more than a somewhat obscure area of study for specialists. In practical terms, this translated into greater numbers of students attracted to the field, increased institutional support for the discipline, and its elevation in status within the biological sciences as new developments, particularly in connection with medical applications, began to draw attention to the field.64The unicellular hypothesis also promoted the internal development of the science. It provided a rationale for introducing the various techniques used in cytology, embryology, physiology, and the new field of biochemistry as suitable research tools for protozoology as well. This vastly extended the research possibilities and facilitated the understanding of, among other things, protozoan organization, modes of reproduction, and evolutionary relationships. The new experimental grounding of the discipline in turn fitted in well with developments in biology at large: in contrast to the descriptive methodology that had predominated in the nineteenth century, this new experimental program placed protozoology at the forefront of the early twentieth-century movement to make biology an experimental science comparable to physics and chemistry.Yet the criticism of the unicellular hypothesis can also be seen as having served a valuable function within the development of the discipline. It focused attention on the study of protists as organisms in their own right, not simply as models for metazoan cells. More generally, it helped to remind biologists of the particular evolutionary assumptions that supported this conception. Dobell and other British critics pointed out, among other things, the association between the theory of recapitulation and the interpretation of protozoa as unicellular organisms. At the time when the recapitulation theory and the germ-layer doctrine were in decline, it was important to stress how these evolutionary ideas also entered into the contemporary concepts of subsidiary specialties. This was as true for protozoology as it was for cell theory itself. The chromidial theory, in its various guises, and the binuclearity hypothesis did in fact contain elements of recapitulationist reasoning, and they were open to criticism for the same kind of overly speculative theorizing that characterized this evolution theory. Dobell's critique forced protozoologists and cell theorists alike to review the theoretical postulates guiding their investigations.In the absence of further historical studies, it is hard to evaluate the consequences of this debate in later years. The issue was not whether protozoa were the precursors of metazoa — both sides accepted this. They disagreed over which particular protozoon had served as the ancestral form, and this, in turn, influenced their stance on the question of unicellularity. The situation is little changed today. Because the former question is still an open one, the latter remains so too. Both of the models for the origin of multicellular organisms — colonies of ciliates versus multinucleate protists — are still presented as possible mechanisms in modern textbooks of evolution. Unable to judge the dispute in terms of the ultimate validity of the competing conceptions, the historian requires other criteria. It perhaps becomes more important to evaluate the issues in the context of the internal and external stimulus they provided the discipline.65 In these terms, and from the present historical vantage point, Hertwig's research program for protozoology, based upon the unicellular hypothesis, appears to have been a successful one. (shrink)

Although the importance of weak protein‐protein interactions has been understood since the 1980s, scant attention has been paid to this “quinary structure”. The transient nature of quinary structure facilitates dynamic sub‐cellular organization through loose grouping of proteins with multiple binding partners. Despite our growing appreciation of the quinary structure paradigm in cell biology, we do not yet understand how the many forces inside the cell – the excluded volume effect, the “stickiness” of the cytoplasm, and hydrodynamic interactions (...) – perturb the weakest functional protein interactions. We discuss the unresolved problem of how the forces in the cell modulate quinary structure, and to what extent the cell has evolved to exert control over the weakest biomolecular interactions. We conclude by highlighting the new experimental and computational tools coming on‐line for in vivo studies, which are a critical next step if we are to understand quinary structure in its native environment. (shrink)

ABSTRACT Recent developments allow for the creation of human stem cells without the creation of human embryos, a process called alternate nuclear transfer (‘ANT’). Pursuing this method of stem cell research makes sense for pro‐lifers if arguments for the sanctity of the human embryo do not apply to ANT. However, the technology that makes ANT possible undermines the erstwhile technical barrier between human embryos and somatic cell DNA. These advances bring home the force of hypothetical arguments about the (...) potential of the DNA in somatic cells, showing that there is not a morally relevant difference between the potential of an embryo and the potential of the DNA in a somatic cell. Therefore, the supposed distinction between entities that are potential human life and entities that are human life does not give any support to arguments for the sanctity of the human embryo because those arguments extend value to too many entities. (shrink)

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit (...) on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations. (shrink)

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit (...) on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations. (shrink)

Background: The regulation of muscle force is a vital aspect of sensorimotor control, requiring intricate neural processes. While neural activity associated with upper extremity force control has been documented, extrapolation to lower extremity force control is limited. Knowledge of how the brain regulates force control for knee extension and flexion may provide insights as to how pathology or intervention impacts central control of movement.Objectives: To develop and implement a neuroimaging-compatible force control paradigm for knee extension and flexion.Methods: A magnetic resonance (...) imaging safe load cell was used in a customized apparatus to quantify force during neuroimaging. Visual biofeedback and a target sinusoidal wave that fluctuated between 0 and 5 N was provided via an MRI-safe virtual reality display. Fifteen right leg dominant female participants completed a knee extension and flexion force matching paradigm during neuroimaging. The force-matching error was calculated based on the difference between the visual target and actual performance. Brain activation patterns were calculated and associated with force-matching error and the difference between quadriceps and hamstring force-matching tasks were evaluated with a mixed-effects model.Results: Knee extension and flexion force-matching tasks increased BOLD signal among cerebellar, sensorimotor, and visual-processing regions. Increased knee extension force-matching error was associated with greater right frontal cortex and left parietal cortex activity and reduced left lingual gyrus activity. Increased knee flexion force-matching error was associated with reduced left frontal and right parietal region activity. Knee flexion force control increased bilateral premotor, secondary somatosensory, and right anterior temporal activity relative to knee extension. The force-matching error was not statistically different between tasks.Conclusion: Lower extremity force control results in unique activation strategies depending on if engaging knee extension or flexion, with knee flexion requiring increased neural activity for the same level of force and no difference in relative error. These fMRI compatible force control paradigms allow precise behavioral quantification of motor performance concurrent with brain activity for lower extremity sensorimotor function and may serve as a method for future research to investigate how pathologies affect lower extremity neuromuscular function. (shrink)

How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell (...) nucleus stiffness on the simulated nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses. (shrink)

Continuous culture techniques were developed in the early twentieth century to replace cumbersome studies of cell growth in batch cultures. In contrast to batch cultures, they constituted an open concept, as cells are forced to proliferate by adding new medium while cell suspension is constantly removed. During the 1940s and 1950s new devices have been designed—called “automatic syringe mechanism,” “turbidostat,” “chemostat,” “bactogen,” and “microbial auxanometer”—which allowed increasingly accurate quantitative measurements of bacterial growth. With these devices cell growth (...) came under the external control of the experimenters and thus accessible for developing a mathematical theory of growth kinetics—developed mainly by Jacques Monod, Aron Novick and Leo Szilard in the early 1950s and still in use today. The paper explores the development of continuous culture devices and claims that these devices are simulators for standard cells following specific requirements, in particular involving mathematical constraints in the design and setting of the devices as well as experiments. These requirements have led to contemporary designs of continuous culture techniques realizing a specific event-based flow algorithm able to simulate directed evolution and produce artificial cells and microorganisms. This current development is seen as an alternative approach to today’s synthetic biology. (shrink)