Many lymphokine genes have now been cloned from activated T cells and their products have been expressed in mammalian cells. Use of these recombinant lymphokines has provided the opportunity to evaluate both the spectrum of their biological activities and the mechanisms of their action in promoting proliferation and differentiation of hemopoietic and lymphoid cells. Characterization of the structure of lymphokine genes will provide information about their regulated expression in T‐cell activation.

This essay offers a theoretical analysis of the changes which are taking place in the musical consciousness of listeners in the present phase of society. The author seeks rather to deduce the conditions of musical reception from the present stage of musical production. The first part of the article deals with changes in production as they affect the general consciousness of listeners. Light music is discussed as well as serious music insofar as it reaches the consumer. Changes in reception are (...) revealed in certain characteristics like the cult of the melody, of the voice, of the master violin, and they are tied up with specific economic concepts. Success plays a particularly important role in this connection.The second part is devoted to the retrogression in listening, analyzed psychologically. Docile passivity, imitation of pre-given patterns, and bitter resentment of the „abnormal“ have become characteristic for the listener. The author shows how this retrogression has become concretized in the formation of a „musical child’s language.“Many listeners seek to overcome passivity by a pseudo-activity. The social function of certain types like the jitter-bug, the radio amateur, or the man with a knack for jazz, are discussed.L’article entreprend d’interpréter sous forme d’une esquisse théorique les transformations qu’a subies la conscience musicale des auditeurs dans la phase actuelle de l’évolution sociale.On n’analyse pas psychologiquement les réactions des auditeurs ; mais on prend pour point de départ Tétât de la production, et de celui-ci on déduit celui de la réception.La première partie traite de la transformation de la production dans la mesure où celle-ci atteint la conscience commune des auditeurs. L’auteur considère aussi bien la musique légère que la soi-disant musique sérieuse et les modifications que connaît celle-ci pour parvenir à la consommation.Ces modifications font de la musique un fétiche. On en prend pour exemple le culte des „idées“ musicales, de la voix et des „violons de maître“. Le caractère fétiche de la musique se mesure au succès accumulé.Ensuite, on développe quelques catégories du fétichisme musical : dépravation, arrangement, „divertissement élevé“, idolâtrie de la perfection.Au fétichisme de la musique correspond du côté de l’auditeur une régression de la faculté d’entendre — phénomène qui fait l’objet de la deuxième partie de l’étude. On l’interprète comme l’attitude auditive caractéristique des „régressifs“. Soumission passive, imitation de l’antérieurement donné, fureur contre ce qui sort de la norme — définissent cette attitude, qui s’objective en un langage musical puéril en formation et dont quelques éléments sont esquissés.A cette passivité, de larges groupes d’auditeurs cherchent vainement à échapper par une pseudo-activité. Quelques types de pseudo-activité sont décrits : l’enthousiaste, le bricoleur et le „chic type“. On montre la fonction sociale de ces types.Enfin, on traite des possibilités dialectiques de l’audition du régressif. Une confrontation de l’expérience fondamentale de la musique radicalement neuve avec le mode régressif d’entendre termine l’article. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Constructive Neutral Evolution is an evolutionary mechanism that can explain much molecular inter-dependence and organismal complexity without assuming positive selection favoring such dependency or complexity, either directly or as a byproduct of adaptation. It differs from but complements other non-selective explanations for complexity, such as genetic drift and the Zero Force Evolutionary Law, by being ratchet-like in character. With CNE, purifying selection maintains dependencies or complexities that were neutrally evolved. Preliminary treatments use it to explain specific genetic and molecular structures (...) or processes, such as retained gene duplications, the spliceosome, and RNA editing. Here we aim to expand the scope of such explanation beyond the molecular level, integrating CNE with Multi-Level Selection theory, and arguing that several popular higher-level selection scenarios are in fact instances of CNE. Suitably contextualized, CNE occurs at any level in the biological hierarchy at which natural selection as normally construed occurs. As examples, we focus on modularity in protein–protein interaction networks or “interactomes,” the origin of eukaryotic cells and the evolution of co-dependence in microbial communities—a variant of the “Black Queen Hypothesis” which we call the “Gray Queen Hypothesis”. (shrink)

J. Willard Gibbs derived the following equation to quantify the maximum work possible for a chemical reaction$${\text{Maximum work }} = \, - \Delta {\text{G}}_{{{\text{rxn}}}} = \, - \left( {\Delta {\text{H}}_{{{\text{rxn}}}} {-}{\text{ T}}\Delta {\text{S}}_{{{\text{rxn}}}} } \right) {\text{ constant T}},{\text{P}}$$ Maximum work = - Δ G rxn = - Δ H rxn - T Δ S rxn constant T, P ∆Hrxn is the enthalpy change of reaction as measured in a reaction calorimeter and ∆Grxn the change in Gibbs energy as measured, if (...) feasible, in an electrochemical cell by the voltage across the two half-cells. To Gibbs, reaction spontaneity corresponds to negative values of ∆Grxn. But what is T∆Srxn, absolute temperature times the change in entropy? Gibbs stated that this term quantifies the heating/cooling required to maintain constant temperature in an electrochemical cell. Seeking a deeper explanation than this, one involving the behaviors of atoms and molecules that cause these thermodynamic phenomena, I employed an “atoms first” approach to decipher the physical underpinning of T∆Srxn and, in so doing, developed the hypothesis that this term quantifies the change in “structural energy” of the system during a chemical reaction. This hypothesis now challenges me to similarly explain the physical underpinning of the Gibbs–Helmholtz equation$${\text{d}}\left( {\Delta {\text{G}}_{{{\text{rxn}}}} } \right)/{\text{dT}} = - \Delta {\text{S}}_{{{\text{rxn}}}} \left( {\text{constant P}} \right)$$ d Δ G rxn / dT = - Δ S rxn constant P While this equation illustrates a relationship between ∆Grxn and ∆Srxn, I don’t understand how this is so, especially since orbital electron energies that I hypothesize are responsible for ∆Grxn are not directly involved in the entropy determination of atoms and molecules that are responsible for ∆Srxn. I write this paper to both share my progress and also to seek help from any who can clarify this for me. (shrink)

Five partly successive and partly overlapping framings have dominated the public debate about human embryonic stem cells since they first were “derived” a decade ago. Geron Corporation staged the initial framings as 1) basic research and 2) medical hope, but these two were immediately refuted and opposed by 3) bioethical concerns, voiced by influential politicians and leaders of opinion. Thereafter, the research community presented adult stem cells and therapeutic cloning as 4) techno-fix solutions supposed to bypass these ethical (...) concerns. And in recent years, 5) institutional limitations to and hurdles within the university–industrial complex (such as patentability, misconduct and fraud) have attracted more attention. The article purifies the arguments and points out the interests and institutions behind the five framings. It also discusses their interplay and finally addresses the question of what happened to the stem cells? (shrink)

The problem we discuss is whether mammalian cells possess genes whose expression is specifically enhanced by DNA damage in order to cope with the damage. The paradigm is the SOS response in E. coli. We conclude that there is compelling evidence that DNA‐damaging agents do affect gene expression, and that mutation frequencies are increased, but proof that a repair process per se is induced remains elusive. We offer here the hypothesis that recognition of the presence of DNA damage by (...) poly(ADPribose) polymerase effects preprogrammed changes in gene expression. (shrink)

The stereotyped pattern of cell commitments during leech embryogenesis is described. The nature of cell commitments during segmentation differs significantly between leech and fruit fly. Despite the constancy of cell fate assignments in normal development, ablation experiments show that cell interactions are essential in setting some of these commitments. Interacting cells follow a positionally determined hierarchy of fate choices. For other cells, which appear to have fates fixed from birth, the possibility of determinative interactions between mother and daughter (...) cells is discussed. (shrink)

During embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well‐characterized cells within a community of different types of cells. Isolation of leech homologues of some of the (...) highly conserved regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type‐specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development. (shrink)

Many of the haemopoietic cell growth factors have now been purified to homogeneity and their structural genes cloned. Methods are also now available for obtaining pure populations of haemopoietic cells. The use of such cells, in combination with pure growth factors, has provided intriguing information about the biological activities and mode of action of the factors in faciliating survival, proliferation and differentiation of the haemopoietic cells.

The extent to which society utilises the law to enforce its moral judgments remains a dominant issue in this era of embryonic stem cell research, preimplantation genetic diagnosis, and human reproductive cloning. Balancing the potential health benefits and diverse moral values of society can be a tremendous challenge. In this context, governments often adopt legislative bans and prohibitions and rely on the inflexible and often inappropriate tool of criminal law. Legal prohibitions in the field of reproductive genetics are not likely (...) to reflect adequately the depth and diversity of competing stakeholder positions. Rather, a comprehensive and readily responsive regulatory policy is required. Such a policy must attend to the evolving scientific developments and ethical considerations. We outline a proposal for effective, responsive, and coherent oversight of new reproductive genetic technologies. (shrink)

Any suggestion of altering the genetic makeup of human beings through gene therapy is quite likely to provoke a response involving some reference to a 'slippery slope'. In this article the author examines the topography of two different types of slippery slope argument, the logical slippery slope and the rhetorical slippery slope argument. The logical form of the argument suggests that if we permit somatic cell gene therapy then we are committed to accepting germ line gene therapy in the future (...) because there is no logically sustainable distinction between them. The rhetorical form posits that allowing somatic cell therapy now will be taking the first step on a slippery slope which will ultimately lead to the type of genocide perpetrated by the Nazis. The author tests the validity of these lines of argument against the facts of human gene therapy and concludes that because of their dependence on probabilities that cannot be empirically proven they should be largely disregarded in the much more important debate on moral line-drawing in gene therapy. (shrink)

The endoplasmic reticulum (ER) organelle is the key intracellular site of both protein and lipid biosynthesis. ER dysfunction, termed ER stress, can result in protein accretion within the ER and cell death; a pathophysiological process contributing to a range of metabolic diseases and cancers. ER stress leads to the activation of a protective signalling cascade termed the Unfolded Protein Response (UPR). However, chronic UPR activation can ultimately result in cellular apoptosis. Emerging evidence suggests that cells undergoing ER stress and (...) UPR activation can release extracellular signals that can propagate UPR activation to target tissues in a cell non‐autonomous signalling mechanism. Separately, studies have determined that the UPR plays a key regulatory role in the biosynthesis of bioactive signalling lipids including sphingolipids and ceramides. Here we weigh the evidence to combine these concepts and propose that during ER stress, UPR activation drives the biosynthesis of ceramide lipids, which are exported and function as cell non‐autonomous signals to propagate UPR activation in target cells and tissues. (shrink)

The model provided by the organismic point of view is quite different. Without having recourse to any transcendent vital force or immanent teleology, it nevertheless rejects the basic ideas of mechanism. More specifically, it replaces the analytical- summative conception by the idea of biological organisms as wholes or systems which have unique system-properties and obey irreducible system-laws. The machine-theoretical conception is replaced by a dynamic interpretation of living things, wherein organic structures are due to a continuous flow of processes combining (...) to produce patterns of immense intricacy. The reaction-theoretical conception is jettisoned in favour of the view that the organism is primarily a center of activity which is autonomous and not a mere response to external stimuli. Finally, the organismic model considers that biological systems are stratified, so that, e.g., viruses, genes, chromosomes, cells, multicellular individuals, supra-individual aggregates, etc., form a hierarchy of "levels" exhibiting an increasing degree of complexity. The whole of nature, indeed, contains "a tremendous architecture, in which subordinate systems are united at successive levels into ever higher and larger systems.". (shrink)

Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short‐range cell–cell signalling molecules, hormones and structural proteins. It has been implicated in a number of key biological processes including cell proliferation, migration, adhesion and signalling both in normal development and in oncogenesis. The mechanisms by which Pax6 regulates its downstream (...) targets likely involve the use of different splice variants and interactions with multiple proteins, allowing it to generate different effects in different cells. Extrapolation to developmental transcription factors in general suggests that variation in the nature of individual factors is likely to contribute to the emergence of differences between tissues. BioEssays 24:1041–1051, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Direct reprogramming of human skin cells makes available a source of pluripotent stem cells without the perceived evil of embryo destruction, but the advent of such a powerful biotechnology entangles stem cell research in other forms of moral complicity. Induced pluripotent stem cell (iPSC) research had its origins in human embryonic stem cell research and the projected biomedical applications of iPS cells almost certainly will require more embryonic stem cell research. Policies that inhibit iPSC research in order (...) to avoid moral complicity are themselves complicit in preventable harms to patients. Moral complicity may be unavoidable, but a Blue Ribbon Panel charged with assessing the need for additional embryonic stem cell lines may ease a transition from embryonic stem cell research to clinical applications of iPS cells. (shrink)

The origin of mitosis and the nuclear envelope were the pivotal processes in the evolutionary origin of the nucleus; they probably occurred in a wall‐less mutant bacterium that evolved a cytoskeleton and phagocytosis about 1500 million years ago. Principles of intracellular coevolution clarify their origin, as well as that of nucleosomes, spliceosomes, and the evolution of genome size.

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short commentary offers a perspective on this (...) debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

Graphical AbstractA cell translocation mechanism displaces sporadic mutant cells from normal, suppressive epithelial environment during early steps of tumor initiation. This epithelial cell translocation process exerts a selective pressure on early mutant cells to survive and grow in new microenvironment outside of their native niches.

Systemic autoimmune diseases are characterized by the production of antibodies against a broad range of self-antigens. Recent evidence indicates that the majority of these autoantigens are modified in various ways during cell death. This has led to the hypothesis that the primary immune response in the development of autoimmunity is directed to components of the dying cell. In this article, we summarize data on the modification of autoantigens during cell death and the possible consequences of this for autoimmunity. BioEssays 22:627–636, (...) 2000. © 2000 John Wiley & Sons, Inc. (shrink)

SummaryHeterozygous 4.1 hereditary elliptocytosis results from the absence of one haploid set of protein 4.1, a major component of the red cell skeleton. Two successive epidemiological investigations revealed fifteen probands in the French Northern Alps. The frequency of this disease seems to be very high in four small villages isolated in the Aravis mountains. The genealogical study shows that eleven probands share common ancestors who lived eight or ten generations ago in these villages. Thus there was probably a founder effect (...) from one pair of ancestors, strengthened by endogamy. In contrast, four probands originate from another area and are not genealogically related. Recent results in molecular genetics support the present data. (shrink)

Classical embryological studies have provided a great deal of information on the autonomy and stability of cell fate determination in early sea urchin embryos. However, these studies were limited by the tools available at the time, and the interpretation of the results of these experiments was limited by the lack of information available at the molecular level. Recent studies which have re‐examined classical experiments at the molecular level have provided important new insights into the mechanism of determination in sea urchins, (...) and require us to re‐evaluate some long standing theories on the process of differentiation. (shrink)

The ATM protein kinase is centrally involved in the cellular response to ionizing radiation (IR) and other DNA double‐strand‐break‐inducing insults. Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic. Now, a landmark paper provides strong evidence that DNA‐strand breaks trigger widespread activation of ATM through changes in chromatin structure.1 This review discusses a checkpoint activation model in which chromatin perturbations lead to the (...) conversion of inactive ATM domains to phosphorylated, active ATM monomers. The new findings underscore the critical importance of epigenetic events in genome function and surveillance in mammalian cells. BioEssays 25:627–630, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

An exploration of the moral and ethical implications of new biotechnologies Many of the ethical issues raised by new technologies have not been widely examined, discussed, or indeed settled. For example, robotics technology challenges the notion of personhood. Should a robot, capable of making what humans would call ethical decisions, be held responsible for those decisions and the resultant actions? Should society reward and punish robots in the same way that it does humans? Likewise, issues of safety, environmental concerns, and (...) distributive justice arise with the increasing acceptance of genetically modified organisms in food production nanotechnology in engineering and medicine, and human gene therapy and enhancement. The problem of dual-use—when a technology can be used both to benefit and to harm—exists with virtually all new technologies but is central in the context of emerging 21st century technologies ranging from artificial intelligence and robotics to human gene-editing and brain-computer interfacing. In Re-Creating Nature: Science, Technology, and Human Values in the Twenty-First Century, James T. Bradley addresses emerging biotechnologies with prodigious potential to benefit humankind but that are also fraught with ethical consequences. Some actually possess the power to directly alter the evolution of life on earth including human. Specifically, these topics include stem cells, synthetic biology, GMOs in agriculture, nanotechnology, bioterrorism, CRISPR gene-editing technology, three-parent babies, robotics and roboethics, artificial intelligence, and human brain research and neurotechnologies. Offering clear explanations of these various technologies, a pragmatic presentation of the conundrums involved, and questions that illuminate hypothetical situations, Bradley guides discussions of these and other thorny issues resulting from the development of new biotechnologies. He also highlights the responsibilities of scientists to conduct research in an ethical manner and the responsibilities of nonscientists to become “science literate” in the twenty-first century. (shrink)

Le 7 novembre 2015, avait lieu à la BNF un colloque confrontant les pensées de René Girard et Michel Henry, intitulé "Le désir de l'Autre". Cette rencontre eut lieu trois jours après le décès de René Girard. Elle fut ainsi pour tous les participants l'occasion de lui rendre hommage. A la suite des confrontations déjà organisées par l'Association Recherches Mimétiques entre René Girard et des penseurs français du XXe siècle (Bourdieu, Levinas, Lévi-Strauss, Derrida, Sartre, etc.), il apparaissait nécessaire de mettre (...) la théorie mimétique en présence, cette fois, de la phénoménologie de Michel Henry, chez qui la question de l'Autre est cruciale. Nos travaux nous ont permis de manifester, peut-être contre toute attente chez des penseurs aux méthodes si différentes, une convergence, voire une complémentarité, dans la définition du désir, dans celle de la nature de la violence qu'il suscite, et aussi dans celle de la possibilité de son dépassement."--Page 4 of cover. (shrink)

Alongside a revival of interest in Thomism in philosophy, scholars have realised its relevance when addressing certain contemporary issues in bioethics. This book offers a rigorous interpretation of Aquinas's metaphysics and ethical thought, and highlights its significance to questions in bioethics. Jason T. Eberl applies Aquinas’s views on the seminal topics of human nature and morality to key questions in bioethics at the margins of human life – questions which are currently contested in the academia, politics and the media such (...) as: When does a human person’s life begin? How should we define and clinically determine a person’s death? Is abortion ever morally permissible? How should we resolve the conflict between the potential benefits of embryonic stem cell research and the lives of human embryos? Does cloning involve a misuse of human ingenuity and technology? What forms of treatment are appropriate for irreversibly comatose patients? How should we care for patients who experience unbearable suffering as they approach the end of life? _Thomistic Principles and Bioethics_ presents a significant philosophical viewpoint which will motivate further dialogue amongst religious and secular arenas of inquiry concerning such complex issues of both individual and public concern. (shrink)

The somatic integration definition of life is familiar from the debate on the determination of death, with some bioethicists arguing that it supports brain death while others argue that some brain‐dead bodies exhibit sufficient somatic integration for biological life. I argue that on either interpretation, the somatic integration definition of life implies that neither the preimplantation embryo nor the postimplantation embryo meet the somatic integration threshold condition for organismal human life. The earliest point at which a somatic integration determination of (...) life could be made would be the beginning of the fetal stage, 9 weeks postfertilization. Bioethical implications are considered, specifically with respect to the moral status of the postimplantation embryo in embryo research and abortion. (shrink)

Philosophers often talk as if what it takes for a person to persist through time were up to us, as individuals or as a linguistic community, to decide. In most ordinary situations it might be fully determinate whether someone has survived or perished: barring some unforeseen catastrophe, it is clear enough that you will still exist ten minutes from now, for example. But there is no shortage of actual and imaginary situations where it is not so clear whether one survives. (...) Here reasonable people may disagree. There are "fission" cases where each of one's cerebral hemispheres is transplanted into a different head; Star-Trek-style "teletransportation" stories; actual cases of brain damage so severe that one can never again regain consciousness, even though one's circulation, breathing, digestion, and other "animal" functions continue; and stories where one's brain cells are gradually removed and replaced by cells from someone else, to name only a few favorites. (shrink)

René Girard est mort dans la semaine qui précéda les attentats du 13 novembre 2015. Il avait écrit : "La violence essentielle revient sur nous de façon spectaculaire, non seulement sur le plan de l'histoire, mais sur le plan du savoir". L'auteur de "La Violence et le sacré" n'est pas un prophète de malheur. Sa pensée donne forme et sens à notre avenir. Il nous faut réentendre sa voix. J'ai dû répondre au choc qu'ont été ces événements conjoints : la (...) mort d'un maître et d'un ami, et les horreurs parisiennes. Ces deux réalités constituent une énigme où se confrontent l'invisible et le monstrueux, le secret et le sacré, l'élégance et l'obscénité. Elles m'ont forcé à évoquer les "derniers jours" : ceux de René Girard et la fin des temps qu'il pensa dans son oeuvre. Beaucoup se sont mépris sur son pessimisme. L'annonce d'un démembrement du monde révélait moins la mélancolie d'un romantique que le Royaume entrevu un soir d'été en Avignon ou dans le silence parfumé de Stanford. J'ai voulu rendre présent ce non-violent fondamental avec qui j'ai travaillé quinze ans, qui fut drôle et discret, dont l'espérance était profonde. La parole est vivante. La sienne et celle des textes qu'il sut génialement interpréter. L'Evangile, Shakespeare, Stendhal ou Proust garderont longtemps pour moi l'accent du Midi. (shrink)

The constancy of the genome structure of an organism has been accepted dogma for a number of decades. The genetic variegation of maize as described by McClintock in the 1940s and subsequently shown to be mediated by transposable elements indicated a degree of genomic fluidity not appreciated previously. The discovery of gene amplification in somatic mammalian cells in 1977 has added a new component to the phenomenon of genomic fluidity, which has implications for various subdisciplines of biology.

In the face of the moral pluralism that results from the death of God and the abandonment of a God's eye perspective in secular philosophy, bioethics arose in a context that renders it essentially incapable of giving answers to substantive moral questions, such as concerning the permissibility of abortion, human embryonic stem cell research, euthanasia, etc. Indeed, it is only when bioethics understands its own limitations and those of secular moral philosophy in general can it better appreciate those tasks that (...) it can actually usefully perform in both the clinical and academic setting. It is the task of this paper to understand and reevaluate bioethics by understanding these limits. Academic bioethicists can analyze ideas, concepts, and claims necessary to understanding the moral questions raised in health care, assessing the arguments related to these issues, and provide an understanding of the different moral perspectives on bioethical issues. In the clinical setting, bioethicists can provide legal advice, serve as experts on IRBs, mediating disputes, facilitating decision-making and risk management, and clarifying normative issues. However, understanding this is only possible when one understands the history, genesis, and foundations of bioethics and its inability to provide a resolution to postmodern moral pluralism. (shrink)

Cellular differentiation is often accompanied by the expression of specialized plasma membrane proteins which accumulate in discrete regions. The biogenesis of these specialized membrane domains involves the assembly and co‐localisation of a spectrin‐based membrane skeleton. While the constituents of the membrane skeleton in non‐erythroid cells are often immunologically related to erythroid spectrin, ankyrin, and protein 4.1, there are structural and functional differences between the isoforms of these membrane skeleton polypeptides, as well as highly variable patterns of expression during cellular (...) differentiation. We consider this heterogeneity of structure and expression during development in the context of the hypothesis that non‐erythroid spectrin, ankyrin, and protein 4.1 are involved in the formation of specialized membrane domains. (shrink)

In this essay I seek to critically evaluate some forms of holism and organicism in biological thought, as a more deflationary echo to Gilbert and Sarkar's reflection on the need for an 'umbrella' concept to convey the new vitality of holistic concepts in biology (Gilbert and Sarkar 2000). Given that some recent discussions in theoretical biology call for an organism concept (from Moreno and Mossio’s work on organization to Kirschner et al.’s research paper in Cell, 2000, building on chemistry to (...) articulate what they called “molecular vitalism,” studying the “vitalistic” properties of molecular, cellular, and organismal function, and Pepper and Herron’s suggestion in their 2008 paper that organisms define a category that evolutionary biology cannot do without), the question, what concept of organicism are they calling for? To what extent are such claims philosophically committed to a non-naturalistic concept of organism as organizing centre, as a foundational rather than heuristic concept – or possibly a “biochauvinism,” to use Di Paolo’s term (Di Paolo 2009)? My aim in this paper is to conceptually clarify the forms of holism and organicism that are involved in these cases (and I acknowledge that the study of early 20th-century holisms [Peterson 2010] indicates that not all of them were in fact ‘organicist’ or ‘biologistic’). I suggest that contemporary holists are still potentially beholden to a certain kind of vitalism or “biochauvinism”; but that when they reduce their claims to mere heuristics, conversely, they risk losing sight of a certain kind of organizational “thickness”, a “vital materiality” (Wheeler 2010) which is characteristic of biological systems (Bechtel 2007). And I ask if it is possible to articulate a concept of biological holism or organicism which is neither an empirical ‘biochauvinism’ nor a metaphysical ‘vitalism’? (shrink)

Superoxide is produced by a NADPH oxidase of phagocytic cells and contributes to their microbicidal activities. The oxidase is activated when receptors in the neutrophil plasma membrane bind to the target microbe. These receptors recognise antibodies and complement fragments which coat the target cell. The oxidase electron transport chain, located in the plasma membrane, comprises a low potential cytochrome b heterodimer (gp 91‐phox and p22‐phox) associated with FAD. It is non‐functional until at least three proteins, p67‐phox, p47‐phox and p21rac (...) (and possibly others), move from the cytosol to dock on the cytochrome b. The docking involves the interaction of SH3 domains may become exposed follwoing phosphorylation of p47‐phox by protein kinase C or, in model systems, by addition of arachidonic acid to reconstitution mixtures. Following the docking process the electron‐transporting component is able to transfer electrons from NADPH to oxygen. This electrogenic event is charge‐compensated by the opening of a prton channel. Components of the oxidase are expressed in non‐phagocytes, where their function is uncretain but could be related to some signal function of superoxide. (shrink)

‘When did I, a human person, begin to exist?’ In developing an answer to this question, I utilize a Thomistic framework, which holds that the human person is a composite of a biological organism and an intellective soul. Eric Olson and Norman Ford both argue that the beginning of an individual human biological organism occurs at the moment when implantation of the zygote in the uterus occurs and the ‘primitive streak’ begins to form. Prior to this point, there does not (...) exist an individual human organism, but a cluster of biological cells which has the potential to split and develop as one or more separate human organisms (identical twinning). Ensoulment (the instantiation of a human intellective soul in biological matter) does not occur until the point of implantation. This conception of the beginning of human personhood has moral implications concerning the status of pre‐implantation biological cell clusters. A new understanding of the beginning of human personhood entails a new understanding of the morality of certain medical procedures which have a direct affect on these cell clusters which contain human DNA. Such procedures discussed in this article are embryonic stem cell research, in vitro fertilization, procured abortion, and the use of abortifacient contraceptives. (shrink)

RÉSUMÉ: Les philosophes de la période moderne sont souvent présentés comme ayant commis une erreur élémentaire: celle de confondre la force propositionnelle avec le contenu propositionnel. Par l'examen de deux cas saillants, à savoir les philosophes de Port-Royal et John Locke, je montre que l'accusation n'est pas fondée, et que Locke en particulier a les ressources requises pour construire une théorie des attitudes propositionnelles.