Somatic mutations arising in human skin cancers are heterogeneously distributed across the genome, meaning that certain genomic regions (e.g., heterochromatin or transcription factor binding sites) have much higher mutation densities than others. Regional variations in mutation rates are typically not a consequence of selection, as the vast majority of somatic mutations in skin cancers are passenger mutations that do not promote cell growth or transformation. Instead, variations in DNA repair activity, due to chromatin organization and transcription factor binding, (...) have been proposed to be a primary driver of mutational heterogeneity in melanoma. However, as discussed in this review here, recent studies indicate that chromatin organization and transcription factor binding also significantly modulate the rate at which UV lesions form in DNA. The authors propose that local variations in lesion susceptibility may be an important driver of mutational hotspots in melanoma and other skin cancers, particularly at binding sites for ETS transcription factors. (shrink)

One central tenet of the Modern Evolutionary Synthesis , and the consensus view among biologists until now, is that all genetic mutations occur by “chance” or at “random” with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the “chance” vs “directed” character of mutations . In fact, some argue that mutations due to a particular kind of (...) mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis’ consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb’s analysis of genetic mutations and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of “evolutionary chance,” which I claim is the Modern Synthesis’ consensus view and a reformulation of Darwin’s most influential idea of “chance” variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis’ paradigm. (shrink)

Receptor oligomerization plays a key role in maintaining genome stability and restricting protein mutagenesis. When properly folded, protein monomers assemble as oligomeric receptors and interact with environmental ligands. In a gene-centered view, the ligand specificity expressed by these receptors is assumed to be causally predetermined by the cell genome. However, this mechanism does not fully explain how differentiated cells have come to express specific receptor repertoires and which combinatorial codes have been explored to activate their associated signaling pathways. It is (...) our contention that the plasma membrane acts as the locus where several contextual cues may be integrated. As such it allows the semiotic selection of those receptor configurations that provide cells with the minimum essential requirements for agency. The occurrence of protein misfolding makes it impossible for receptor monomers to assemble along the membrane and to sustain meaningful relationships with environmental ligands. How could a cell lineage deal with these loss-of-function mutations during evolution and restrain gene redundancy accordingly? In this paper, we will be arguing that the easiest way for bacteria clones to accomplish this goal is by getting rid of cells expressing mutated receptor proteins. The mechanism sustaining this cell selection is also occurring in many somatic tissues and its function is currently believed to counteract in vivo protein mutagenesis. Our discussion will be mainly focused on the significance and semiotic nature of the interplay between membrane receptors and the epigenetic control of gene expression, as mediated by the control of mismatched repairing and protein folding mechanisms. (shrink)

There is evidence that asexual reproduction has a long-term disadvantage when compared to sexual reproduction. This disadvantage is usually assumed to arise from the more efficient incorporation of advantageous mutations by sexual populations. We consider here the effect on asexual and sexual populations of changes in the fitness of harmful mutations. It is shown that the re-establishment of equilibrium following environmental change is generally faster in sexual populations, and that the mutational load experienced by the sexual population can be significantly (...) less during this period than that experienced by an asexual one. Changes in the fitness of harmful mutations may therefore impose a greater long-term disadvantage on asexual populations than those which are sexual. (shrink)

Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. (...) Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress‐ or mutation‐induced chromosomal instability, fueling rapid cellular adaptation. (shrink)

A great deal is known about the technical issues surrounding the introduction of Hugo De Vries's mutation theory and the subsequent development of the modern genetical theory of natural selection. But so far little has been done to relate these events to the wider issues of the time. This article suggests that extra-scientific factors played a significant role, and substantiates this by comparing De Vries's respect for the original Darwinian spirit with Thomas Hunt Morgan's use of the mutation (...) theory as part of an attack on the whole philosophy of Darwinism. In particular, it is argued that Morgan's attitude was dictated by his moral objections to the picture of a world dominated by struggle. (shrink)

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions (mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}) have a replicative advantage over wild-type (mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}) and that this is detrimental to the host cell, especially in (...) post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} would compete with the mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} compete with mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} such that the cell expires upon mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} do have a replicative advantage over mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}. As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}. Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset. (shrink)

It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional significance. The so‐called (...) “ectopic” expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by‐product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities. BioEssays 27:592–601, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

An experiment teacher of elementary school try te become an educational adviser. He accepts the collaboration with the researchers, the first one in didactics of history and the second in professional didactics, to get success with examination necessary to become an educational adviser. The didactic experiment concerns an historical debate with pupils to orient them in an historic investigation from an engraving dating from 1787. The analyse shows that the didactic experiment was abandoned for the benefit of institutional prescriptions in (...) which this teacher aims to conforms, its principles of actions and the significantly associations with his future job. It’s in contradiction with the sens of the activity proposed by the researcher in didactics of history. Our longitudinal analysis concerns, first, the teacher analyses the activity of a beginner, second, the experimentation of the debate in his classroom and finally his theorization about the driving of this type of debate in a document required in the examination. (shrink)

How were the concepts of the observer and user in architecture and urban planning transformed throughout the 20th and 21st centuries? Marianna Charitonidou explores how the mutations of the means of representation in architecture and urban planning relate to the significance of city's inhabitants. She investigates Le Corbusier and Ludwig Mies van der Rohe's fascination with perspective, Team Ten's interest in the humanisation of architecture and urbanism, Constantinos Doxiadis and Adriano Olivetti's role in reshaping the relationship between politics and (...) urban planning during the postwar years, Giancarlo De Carlo's architecture of participation, Aldo Rossi's design methods, Denise Scott Brown's active socioplactics and Bernard Tschumi's conception praxis. (shrink)

Diagnostik und Klassifikation der akuten myeloischen Leukämie (AML) beruhen auf zytologischen und zytogenetischen Charakteristika. Eine Individualisierung der Diagnostik und Therapie wird für AML mit normalem Karyotyp (CN-AML) durch den Nachweis spezifischer Genmutationen zunehmend ermöglicht. In einem systematischen Literaturreview und Metanalyse wurde die Mutation FLT3-ITD bei CN-AML untersucht. Eine systematische Literaturrecherche aller Veröffentlichungen der Datenbanken Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge und Cochrane wurde für den Zeitraum 2000 bis März 2012 im Hinblick auf die Mutation FLT3-ITD bei (...) Patienten mit CN-AML und einem Alter von 15–65 Jahren durchgeführt. Der Literaturrecherche folgte eine Literaturselektion, eine Datenextraktion und eine qualitative sowie quantitative Informationssynthese in Form einer Metaanalyse. Achtzehn Veröffentlichungen konnten in die qualitative Analyse zur CN-AML eingeschlossen werden. Daten von 3 Publikationen zum Gesamtüberleben mit insgesamt 1.203 Patienten gingen mit Bezug auf den Marker FLT3-ITD in die Metaanalyse ein. Für FLT3-ITD zeigte sich eine statistisch signifikante schlechtere Prognose mit einer hazard ratio von 2,19 für das Gesamtüberleben bei CN-AML. FLT3-ITD ist im Vergleich zum Wildtyp mit einer schlechteren Prognose in Bezug auf den Krankheitsverlauf bei AML assoziiert. Die Analyse von FLT3 sollte bei der AML berücksichtigt werden. (shrink)

Alternative pre‐mRNA splicing leads to distinct products of gene expression in development and disease. Antagonistic splice variants of genes involved in differentiation, apoptosis, invasion and metastasis often exist in a delicate equilibrium that is found to be perturbed in tumours. In several recent examples, splice variants that are overexpressed in cancer are expressed as hyper‐oncogenic proteins, which often correlate with poor prognosis, thus suggesting improved diagnosis and follow up treatment. Global gene expression technologies are just beginning to decipher the interplay (...) between alternatively spliced isoforms and protein‐splicing factors that will lead to identification of the mutations in these trans‐acting factors responsible for pathogenic alternative splicing in cancer. BioEssays 28: 378–386, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Comparative studies of DNA sequences provide opportunities for testing the neutral and the selection theories of molecular evolution. In particular, the separate estimation of the numbers of synonymous and nonsynonymous substitutions is a powerful tool for detecting selection of the latter. The difference in the patterns of these two types of substitutions of mammalian genes turned out to be in accord with the slightly deleterious or nearly neutral mutation theory for nonsynonymous changes. Interaction systems at the amino acid level (...) were suggested to be responsible for such nearly neutral, or very weak, selection. Synonymous substitutions are not strictly neutral, but because of their minute effect, random drift predominates such that the rate of substitution is only slightly less than the completely neutral prediction. It was concluded that the strictly neutral theory has not held up as well as the nearly neutral theory, yet remains invaluable as a null hypothesis for detecting selection. On the other hand, the main difference between the nearly neutral and the traditional selection theories is that the former predicts rapid evolution in small populations, whereas the latter predicts rapid evolution in large populations. (shrink)

Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2, and mutations that disrupt complex function and/or (...) formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases. (shrink)

Rho proteins belong to the small GTPases superfamily. They function as molecular switches that, in response to diverse stimuli, control key signaling and structural aspects of the cell. Although early studies proposed a role for Rho GTPases in cellular transformation, this effect was underestimated due to the fact that no genetic mutations affecting Rho‐encoding genes were found in tumors. Recently, it has become evident that Rho GTPases participate in the carcinogenic process by either overexpression of some of the members of (...) the family with oncogenic activity, downmodulation of other members with suggested tumor suppressor activity, or by alteration of upstream modulators or downstream effectors. Thus, alteration of the levels of expression of different members of the family of Rho GTPases has been detected in many types of human tumors leading to a great interest in the cellular effects elicited by these oncoproteins. This essay reviews the current evidence of dysregulation of Rho signaling by overexpression in human tumors. BioEssays 27:602–613, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

This article describes the historical emergence of vital systems security, analyzing it as a significant mutation in biopolitical modernity. The story begins in the early 20th century, when planners and policy-makers recognized the increasing dependence of collective life on interlinked systems such as transportation, electricity, and water. Over the following decades, new security mechanisms were invented to mitigate the vulnerability of these vital systems. While these techniques were initially developed as part of Cold War preparedness for nuclear war, they (...) eventually migrated to domains beyond national security to address a range of anticipated emergencies, such as large-scale natural disasters, pandemic disease outbreaks, and disruptions of critical infrastructure. In these various contexts, vital systems security operates as a form of reflexive biopolitics, managing risks that have arisen as the result of modernization processes. This analysis sheds new light on current discussions of the government of emergency and ‘states of exception’. Vital systems security does not require recourse to extraordinary executive powers. Rather, as an anticipatory technology for mitigating vulnerabilities and closing gaps in preparedness, it provides a ready-to-hand toolkit for administering emergencies as a normal part of constitutional government. (shrink)

The significance of educational research is today predicated on its ability to engage with the ecological, economic, and political challenges of the anthropocene, for where we might take seriously education’s commitment to the future necessitates a sustained encounter with the implications and questions raised in the wake of ‘our’ mutated planetary ecology. To repeat in the image of those educational practices, models and patterns of thinking that have contributed to the contemporary ecological crisis of the planet falls gravely short (...) of apprehending what it might entail to live in the contemporary moment. Yet further, where education is intimate to teleology, it is today clear that the image of the future posited educationally has fallen out of synch with the ‘outside thought’ of ecocatastrophe, or rather, our being ‘thought’ from the inhuman perspective of a planet destined to go on without us. Educationally, this threat poses a quite remarkable opportunity, for where human thought might be doomed to extinction, the question of how and where we might think assumes urgency. In this vein, this essay explores the wisdom that ‘we’ are and will be thought from perspectives alien to human desire becomes a catalyst for how educational research might be rethought otherwise in a more-than-human world. (shrink)

This article describes how empirical discoveries in the 1930s–1950s regarding population variation for chromosomal inversions affected Theodosius Dobzhansky and Richard Goldschmidt. A significant fraction of the empirical work I discuss was done by Dobzhansky and his coworkers; Goldschmidt was an astute interpreter, with strong and unusual commitments. I argue that both belong to a mechanistic tradition in genetics, concerned with the effects of chromosomal organization and systems on the inheritance patterns of species. Their different trajectories illustrate how scientists’ commitments affect (...) how they interpret new evidence and adjust to it. Dobzhansky was moved to revised views about selection, while Goldschmidt moved his attention to different genetic phenomena. However different, there are significant connections between the two that enrich our understanding of their views. I focus on two: the role of developmental considerations in Dobzhansky’s thought and the role of neutrality and drift in Goldschmidt’s evolutionary account. Dobzhansky’s struggle with chromosomal variation is not solely about competing schools of thought within the selectionist camp, as insightfully articulated by John Beatty, but also a story of competition between selectionist thinking and developmental perspectives. In contraposition, Goldschmidt emphasized the role of low penetrance mutations that spread neutrally and pointed out that drift could result from developmental canalization. This account adds to the dominant story about Goldschmidt’s resistance to the splitting of development from genetics, as told by Garland Allen and Michael Dietrich. The story I tell illustrates how developmental thinking and genetic thinking conflicted and influenced researchers with different convictions about the significance of chromosomal organization. (shrink)

Adaptive phenotypic plasticity allows organisms to cope with environmental variability, and yet, despite its adaptive significance, phenotypic plasticity is neither ubiquitous nor infinite. In this review, we merge developmental and population genetic perspectives to explore costs and limits on the evolution of plasticity. Specifically, we focus on the role of modularity in developmental genetic networks as a mechanism underlying phenotypic plasticity, and apply to it lessons learned from population genetic theory on the interplay between relaxed selection and mutation (...) accumulation. We argue that the environmental specificity of gene expression and the associated reduction in pleiotropic constraints drive a fundamental tradeoff between the range of plasticity that can be accommodated and mutation accumulation in alternative developmental networks. This tradeoff has broad implications for understanding the origin and maintenance of plasticity and may contribute to a better understanding of the role of plasticity in the origin, diversification, and loss of phenotypic diversity. (shrink)

Heritage values are basic in conservation, nevertheless there is not a methodology to analyze their variation over time and how it has affected the conservation of heritage assets. Therefore, a methodology that allows us to determine their variation in written descriptions about a specific heritage site was needed. In this article we have addressed the concept of heritage values and stressed their importance and their variability over time, but also analyzed different methods from the field of linguistics that would better (...) adapt to determine heritage values variation and their application in the heritage field. (shrink)

Diploid germ cells produce haploid gametes through meiosis, a unique type of cell division. Independent reassortment of parental chromosomes and their recombination leads to ample genetic variability among the gametes. Importantly, new mutations also occur during meiosis, at frequencies much higher than during the mitotic cell cycles. These meiotic mutations are associated with genetic recombination and depend on double‐strand breaks (DSBs) that initiate crossing over. Indeed, sequence variation among related strains is greater around recombination hotspots than elsewhere in the genome, (...) presumably resulting from recombination‐associated mutations. Significantly, enhanced mutagenicity in meiosis may lead to faster divergence during evolution, as germ‐line mutations are the ones that are transmitted to the progeny and thus have an evolutionary impact. The molecular basis for mutagenicity in meiosis may be related to the repair of meiotic DSBs by polymerases, or to the exposure of single‐strand DNA to mutagenic agents during its repair. (shrink)

This paper explores the significance of Heraclitus’s fragment B45 for Husserl and Merleau-Ponty as it appears in the Crisis of the European Sciences and Merleau-Ponty’s lectures on this text in the late 1950s. I claim that at stake is a revision or mutation of the sense of transcendentality: by naming it psyche, the transcendental is no longer understood as a static set of a priori conditions but what I call, following Jean-Luc Nancy, “outsidedness.” I elaborate this idea in (...) dialogue with Nancy and Derrida in their texts “De l’âme” and On Touching: Jean-Luc Nancy. By identifying the sense of transcendentality with the psyche of Heraclitus, we see a transcendentality in the process of departing, and hence transcendentality is an event for which we always arrive late.Cet article explore la signification du fragment B45 de Héraclite pour Husserl et Merleau-Ponty telle qu’elle apparaît dans la Crise des Sciences Européennes et dans la lecture de ce texte par Merleau-Ponty à la fin des années 1950. Je postule qu’il en va de la révision ou de la mutation du sens de la « transcendantalité » : en l’appelant psyche, le transcendantal n’est plus compris comme un ensemble statique de conditions a priori mais comme ce que je nomme, suivant Jean-Luc Nancy, un « au-delà ». J’élabore cette idée en dialogue avec les textes de Nancy et de Derrida : « De l’âme » et Le Toucher, Jean-Luc Nancy. En identifiant le sens de la « transcendantalité » avec la psyche de Héraclite, nous remarquons une « transcendantalité » sur le départ, et donc la « transcendantalité » est un événement pour lequel nous arrivons toujours en retard. Questo saggio esplora il significato del frammento di Eraclito B45 per Husserl e Merleau-Ponty, per come appare nella Crisi delle scienze europee e nella lettura merleau-pontiana di questo testo verso la fine degli anni Cinquanta. Ci sembra di poter affermare che in gioco vi sia una rivisitazione, una mutazione, del senso del trascendentale: definendolo come psyche, il trascendentale non è più concepito come una serie statica di condizioni a priori, ma come ciò che, con Jean-Luc Nancy, chiamiamo “esteriorità”. Abbiamo elaborato questa idea in dialogo con Nancy e Derrida e i loro testi rispettivi Dell’anima e Toccare, Jean-Luc Nancy. Identificando il senso della trascendentalità con la psyche di Eraclito, possiamo vedere della trascendentalità nel processo del dipartirsi (partance), e quindi, proprio in questo senso, comprendere la trascendentalità come un evento rispetto al quale siamo sempre in ritardo. (shrink)

Of the many genes mutated on the road to tumor formation, few have received as much attention as p53. The gene has come to occupy center stage for the simple reason that it is more frequently altered in human tumors than any other known gene, undergoing mutation at a significant rate in almost every tumor type in which it has been studied. This association between p53 mutation and tumorigenesis has spurred a flurry of research attempting to delineate the (...) normal function of p53 and, by extension, the role of p53 mutation in tumor formation. At the cellular level, p53 has been shown to suppress growth. Recent efforts to further discern the function of p53 have centered on the underlying molecular basis for this growth suppression. In particular, research has focused on the identification of cellular molecules (specifically DNA and proteins) with which the p53 protein associates. p53 has now been shown to bind DNA in a sequence‐specific manner, and mounting evidence suggests that p53 acts as a transcription factor, perhaps regulating the expression levels of genes involved in the inhibition of cell growth. The logical next step in understanding p53 function involves the resolution of two questions: (1) what are the physiological transcriptional targets of p53, and (2) what cellular proteins regulate or mediate the ability of p53 to modulate transcription? Some initial clues to these puzzles are now emerging, and these form the subject of this review. (shrink)

The Politics of Method in the Human Sciences provides a remarkable comparative assessment of the variations of positivism and alternative epistemologies in the contemporary human sciences. Often declared obsolete, positivism is alive and well in a number of the fields; in others, its influence is significantly diminished. The essays in this collection investigate its mutations in form and degree across the social science disciplines. Looking at methodological assumptions field by field, individual essays address anthropology, area studies, economics, history, the philosophy (...) of science, political science and political theory, and sociology. Essayists trace disciplinary developments through the long twentieth century, focusing on the decades since World War II. Contributors explore and contrast some of the major alternatives to positivist epistemologies, including Marxism, psychoanalysis, poststructuralism, narrative theory, and actor-network theory. Almost all the essays are written by well-known practitioners of the fields discussed. Some essayists approach positivism and anti-positivism via close readings of texts influential in their respective disciplines. Some engage in ethnographies of the present-day human sciences; others are more historical in method. All of them critique contemporary social scientific practice. Together, they trace a trajectory of thought and method running from the past through the present and pointing toward possible futures. Contributors. Andrew Abbott, Daniel Breslau, Michael Burawoy, Andrew Collier , Michael Dutton, Geoff Eley, Anthony Elliott, Stephen Engelmann, Sandra Harding, Emily Hauptmann, Webb Keane, Tony Lawson, Sophia Mihic, Philip Mirowski, Timothy Mitchell, William H. Sewell Jr., Margaret R. Somers, George Steinmetz, Elizabeth Wingrove. (shrink)

Evolutionary epistemology has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework. In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: ontogenetic considerations, key ideas from cognitive biology, and the framework of the Extended Evolutionary Synthesis. EE, in particular the program of the evolution of epistemological mechanisms, seeks to provide a phylogenetic account of (...) the generation of cognitive processes underlying knowledge creation. Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM’s agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution and can provide a more suitable framework for EEM to draw from. In recent years, cognitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a “vertical” approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a “horizontal” approach that focuses on phylogenetic explanations of cognition and knowledge acquisition. Linking EEM with the key ideas of cognitive biology could make EEM’s research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories and understands the increase in human knowledge, such as scientific theories, as naturalistic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adaptationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution. (shrink)

In this paper we explore the rise of ‘the breast cancer gene’ as a field of medical, cultural and personal knowledge. We address its significance in the Norwegian public health care system in relation to so-called biological citizenship in this particular national context. One of our main findings is that, despite its claims as a measure for health and disease prevention, gaining access to medical knowledge of BRCA 1/2 breast cancer gene mutations can also produce severe instability in the (...) individuals and families affected. That is, although gene testing provides modern subjects with an opportunity to foresee their biological destiny and thereby become patients in waiting, it undoubtedly also comes with difficult existential dilemmas and choices, with implications that resonate beyond the individual and into different family and love relations. By elaborating on this finding we address the question of whether the empowerment slogan, which continues to be advocated through various health, BRCA and breast cancer discourses, reinforces a naïve or an idealized notion of the actively responsible patient: resourceful enough to seek out medical expertise and gain sufficient knowledge, on which to base informed decisions, thereby reducing the future risk of developing disease. In contrast to this ideal, our Norwegian informants tell a different story, in which there is no apparent heroic mastery of genetic fates, but rather a pragmatic attitude to dealing with a dire situation over which they have little control, despite having complied with medical advice through national guidelines and follow-up procedures for BRCA 1/2 carriers. In conclusion we claim that the sense of safety that gene testing and its associated medical solutions allegedly promise to provide proved illusory. Although BRCA-testing offers the potential for protection from adverse DNA-heritage, administered through possibilities for self-monitoring and self-management of the body, the feeling of ‘being in good health’ has hardly been reinforced by the emergence of gene technology. (shrink)

A major challenge for The Cancer Genome Atlas (TCGA) Project is solving the high level of genetic and epigenetic heterogeneity of cancer. For the majority of solid tumors, evolution patterns are stochastic and the end products are unpredictable, in contrast to the relatively predictable stepwise patterns classically described in many hematological cancers. Further, it is genome aberrations, rather than gene mutations, that are the dominant factor in generating abnormal levels of system heterogeneity in cancers. These features of cancer could significantly (...) reduce the impact of the sequencing approach, as it is only when mutated genes are the main cause of cancer that directly sequencing them is justified. Many biological factors (genetic and epigenetic variations, metabolic processes) and environmental influences can increase the probability of cancer formation, depending on the given circumstances. The common link between these factors is the stochastic genome variations that provide the driving force behind the cancer evolutionary process within multiple levels of a biological system. This analysis suggests that cancer is a disease of probability and the most‐challenging issue to the TCGA project, as well as the development of general strategies for fighting cancer, lie at the conceptual level. BioEssays 29:783–794, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Transcription factor binding sites (TFBSs) on the DNA are generally accepted as the key nodes of gene control. However, the multitudes of TFBSs identified in genome‐wide studies, some of them seemingly unconstrained in evolution, have prompted the view that in many cases TF binding may serve no biological function. Yet, insights from transcriptional biochemistry, population genetics and functional genomics suggest that rather than segregating into ‘functional’ or ‘non‐functional’, TFBS inputs to their target genes may be generally cumulative, with varying degrees (...) of potency and redundancy. As TFBS redundancy can be diminished by mutations and environmental stress, some of the apparently ‘spurious’ sites may turn out to be important for maintaining adequate transcriptional regulation under these conditions. This has significant implications for interpreting the phenotypic effects of TFBS mutations, particularly in the context of genome‐wide association studies for complex traits. (shrink)

This paper draws on the philosophy of Karl Popper to present a descriptive evolutionary epistemology that offers philosophical solutions to the following related problems: ‘What happens when learning takes place?’ and ‘What happens in human learning?’ It provides a detailed analysis of how learning takes place without any direct transfer of information from the environment to the learner, and it significantly extends the author's earlier published work on this topic. She proposes that learning should be construed as a special case (...) of ‘problem solving’ and as a fundamentally critical and creative process in which learning organisms develop ‘expectations’ that are not purely an outcome of genetic inheritance or random mutation. Human learning is then characterised with reference to: objectified knowledge; descriptive and argumentative language; theoretical problems; the search for error and specific limitation. If the author's evolutionary analysis of learning is valid, it would suggest that we should, if we wish to promote learning, be wary of corralling children and older students in environments that inhibit autonomous activity, that discourage criticality and creativity and generally limit opportunities for trial and error‐elimination. But education institutions, particularly those for older children and adolescents, are very often environments of this constraining kind. Traditionally, educationists have vastly underestimated the human potential for imaginative criticism—because in general they have not recognised the extent to which it lies at the heart of what humans, including the youngest children, do in order to succeed at even the most basic tasks. (shrink)

While its mechanism and biological significance are unknown, the utility of a short mitochondrial DNA sequence as a “barcode” providing accurate species identification has revolutionized the classification of organisms. Since highest accuracy was achieved with recently diverged species, hopes were raised that barcodes would throw light on the speciation process. Indeed, a failure of a maternally donated, rapidly mutating, mitochondrial genome to coadapt its gene products with those of a paternally donated nuclear genome could result in developmental failure, thus (...) creating a post-zygotic barrier leading to reproductive isolation and sympatric branching into independent species. However, the barcode itself encodes a highly conserved, species-invariant, protein, and the discriminatory power resides in the non-amino acid specific bases of synonymous codons. It is here shown how the latter could register changes in the oligonucleotide frequencies of nuclear DNA that, when they fail to match in pairing meiotic chromosomes, could reproductively isolate the parents so launching a primary divergence into two species. It is proposed that, while not itself contributing to speciation, the barcode sequence provides an index of the nuclear DNA oligonucleotide frequencies that drive speciation. (shrink)

Alzheimer disease is a huge and growing societal problem with upwards of 35% of the population over the age of 80 developing the disease. AD results in a loss of memory, the ability to make reasoned and sound decisions, and ultimately the inability to take care of oneself. AD has an impact not only on the sufferer, but their caretakers and loved ones, who must take on a costly and time-consuming burden of care. AD is found in virtually all racial (...) and ethnic groups. Genetic influences on AD are substantial, and there has been a 30 year history of both success and failure. Mutations for rare early onset forms of the disease have been identified, but this information has not yet led to an effective treatment. Multiple common genetic variations have also been identified, and have led to new insights into the potential role of microglia cells in addition to neuronal cells in the brain. Despite intensive efforts, a significant portion of the genetic etiology of AD remains unknown and must be identified. (shrink)

This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel, a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova, who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found (...) no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel’s subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War. (shrink)

Elliott Sober and his defenders think of selection, drift, mutation, and migration as distinct evolutionary forces. This paper exposes an ambiguity in Sober's account of the force of selection: sometimes he appears to equate the force of selection with variation in fitness, sometimes with ‘selection for properties’. Sober's own account of fitness as a property analogous to life-expectancy shows how the two conceptions come apart. Cases where there is selection against variance in offspring number also show that selection and (...) drift cannot be distinguished in the way Sober hopes for. These issues have significance beyond the parochial matter of the coherence of Sober's system. There is no good principled answer to the question of which features of a population should count among the contributors to fitness. This means there is no non-arbitrary account of the nature of selection. (shrink)

The chapter examines the recent approach to ideology as an actual and ubiquitous combination of decontested political concepts, whose micro-morphological arrangements are the key to the specific meaning each ideological family contains. Shifting proximities and relative weights accorded to those concepts produce multiple ideological variants. Ideologies are pivotal to the discipline of political theory, discernible both in professional and vernacular thinking, and serve as discursive competitions over the control of public political language. Notions of essential contestability, theories of symbolic mapping, (...) and a focus on actual rather than normative political thinking shed light on their semantic significance. Ideologies are permanent phenomena ranging from the flexible to the rigid, and the boundaries that seem to separate one ideology from another may be loose and mutating, challenging the traditional association of ideologies with political parties. In parallel, the study of ideology involves decoding and interpretation, not its juxtaposition with truth. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Removing the Mask: Hopeless Isolation to Intersex AdvocacyAlexandra von KlanStrangers undoubtedly perceive me as female, but I identify as an intersex woman. My karyotype is 46,XY, a typically defined marker of male biological sex, and I was born with undeveloped, non–functioning gonads. As an intersex person, I know firsthand the negative consequences of pathologizing intersex people’s lived experience by categorizing otherwise healthy, functioning organs and bodies as abnormal. The (...) following narrative recounts conversations and interactions with medical providers during my diagnosis and subsequent treatment of pure XY gonadal dys-genesis, sometimes referred to as Swyer Syndrome. I hope to elaborate upon emotionally significant actions and inactions of medical care providers to expose consequential effects on my emotional processing, physical health, and self–actualization.In December 1988, I was born with “typical” female genitalia. No one knew I was an intersex woman with 46,XY karyotype. Thus, there was no hesitation in the announcement of the birth of a girl in the delivery room or later, on my birth certificate. My parents raised me as a girl and dressed their firstborn in culturally normative feminine garments and accessories: lace frilly frocks, oversized bows, white stockings, and black patent leather Mary Jane’s. I embraced femininity and expressed this gender identity throughout my childhood and adolescence. I’m the eldest of six children split between two households.In January 2005, a month after my sixteenth birthday, delayed puberty and absent menstruation prompted an appointment to a local women’s health center. Nurses collected blood samples and administered an MRI scan on my pelvic region. A week later, my father received a perplexing phone call. An inexperienced doctor told him “there must be something wrong” with me, because lab results revealed I was “chromosomally male.” My father recalls the information presented like, based on the evidence, “your daughter may not be completely female,” and that is that. His impression was that she knew little about the subject and was a bit clueless. She did not mention Swyer Syndrome, or any diagnosis for that matter.Up to this point, I was unaware that a member of my extended family also had Swyer Syndrome. Born in the 1950s, secrecy engulfed her medical treatment and doctors warned her parents against revealing her true chromosomal sex in order to prevent the hysterical panic and depression they [End Page E14] thought the truth would bring. Years later, she sought her medical records and unearthed the truth. Shortly after my father received that dubious phone call, my relative’s endocrinologist provided a referral to his mentor, “Doctor A,” a clinical reproductive endocrinologist.Under Doctor A’s care, I experienced the first of many pelvic exams. Much to my discomfort, Doctor A inspected my semi–clothed body with a male resident in the room. As a people–pleasing teen, I granted permission for his presence; I didn’t voice my preference for a female alternative. Doctor A’s cold hands pressed around each undeveloped breast, pulled a gown away from my hips to inspect a sparse patch of pubic hair, and conducted an examination of my vaginal canal.Shortly after the examination, Doctor A charted Swyer Syndrome as the official diagnosis. Speaking to my father and me, he described my condition as an extremely rare genetic mutation. He told us that Swyer Syndrome was an intersex condition, a group of congenital disorders impacting a person’s internal or external reproductive systems, including endocrine function and genitalia. He explained I had atypical streak gonads instead of ovaries and that, despite having typical male sex chromosomes, I was still very much a girl. He disclosed that my vaginal canal was moderate in length, perhaps further evidence—or consolation—that my body possessed normative female reproductive attributes after all.Next, Doctor A identified a pressing medical concern—golf–ball–sized benign tumors had developed on each streak gonad; if allowed to remain, they would pose an increasing risk of malignancy. We scheduled an appointment for laparoscopic gonadectomy six months later. I left his office with a 3–month prescription for estrogen and progesterone oral tablets. On the way home, we drove to an electronics store where my father... (shrink)

The paper is primarily devoted to Nietzsche’s account of cruelty, which represents an indispensable key to understanding Nietzsche’s genealogical project in many of its essential aspects. This study is complemented by parallels with two other outstanding intellectual figures of the late nineteenth century: Fyodor Mikhailovich Dostoevsky and Leopold von Sacher-Masoch. Dostoevsky wrote that “civilisation has made mankind if not more bloodthirsty, at least more vilely, more loathsomely bloodthirsty.” Nietzsche went a step further in this assessment: not only does civilisation not (...) make us immune to cruelty, but it must itself be seen to emerge directly from cruelty at every significant step it has taken. What brings Nietzsche close to Masoch, on the other hand, is the fact that these historical or even prehistorical developments that have shaped humankind and civilisation are not only related to cruelty, but must be observed as various forms of the internalisation (“spiritualisation”, “deification”) of cruelty. The core of the study is devoted to analyses of different forms and aspects of Nietzsche’s concept of the internalisation of cruelty (in relation to power-relations, subject-object relations, mutations of pleasure, and perversions). (shrink)

For both vertebrate developmental and evolutionary biologists, and also for clinicians, the neural crest (NC) is a fundamental cell population. An understanding of Sox10 function in NC development is of particular significance since Sox10 mutations underlie several neurocristopathies. Surprisingly, experiments in different model organisms aimed at identifying Sox10's role(s) have suggested at least four distinct functions. Sox10 may be critical for formation of neural crest cells (NCCs), maintaining multipotency of crest cells, specification of derivative cell fates from these cells (...) and their differentiation. Here, I discuss this controversy and argue that these functions are, in part, molecularly interrelated. BioEssays 28: 788–798, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The use of Next Generation Sequencing such as Whole Genome Sequencing is a promising step towards a better understanding and treatment of neurological diseases. WGS can result into unexpected information, and information with uncertain clinical significance. In the context of a Genome Canada project on ‘Personalized Medicine in the Treatment of Epilepsy’, we intended to address these challenges surveying neurologists’ opinions about the type of results that should be returned, and their professional responsibility toward recontacting patients regarding new discovered (...) mutations. Potential participants were contacted through professional organizations or direct invitations. A total of 204 neurologists were recruited. Fifty nine percent indicated that to be conveyed, WGS results should have a demonstrated clinical utility for diagnosis, prognosis or treatment. Yet, 41% deemed appropriate to return results without clinical utility, when they could impact patients’ reproductive decisions, or on patients’ request. Current use of targeted genetic testing and age of patients influenced respondents’ answers. Respondents stated that analysis of genomics data resulting from WGS should be limited to the genes likely to be relevant for the patient’s specific medical condition, so as to limit IFs. Respondents felt responsible to recontact patients and inform them about newly discovered mutations related to the medical condition that triggered the test for as long as they are following up on the patient. Finally, 53.5% of the respondents felt responsible to recontact and inform patients of clinically significant, newly discovered IFs. Our results show the importance of formulating professional guidelines sensitive to the various – and sometimes opposite – viewpoints that may prevail within a same community of practice, as well as flexible so as to be attuned to the characteristics of the neurological conditions that triggered a WGS. (shrink)

In this paper we show that there are certain limits as to what applications of Maynard Smith’s concept of evolutionarily stable strategy can tell us about evolutionary processes. We shall argue that ESS is very similar in spirit to a particular branch of rational choice game theory, namely, the literature on refinements of Nash equilibrium. In the first place, ESS can also be viewed as a Nash equilibrium refinement. At a deeper level, ESS shares a common structure with other rational (...) choice equilibrium refinements. An equilibrium is evaluated according to whether it persists under specific kinds of perturbations. In the case of ESS, these perturbations are mutations. However, from a dynamical point of view, focusing exclusively on perturbations of equilibria provides only a partial account of the system under consideration. We will show that this has important consequences when it comes to analyzing game-theoretic models of evolutionary processes. In particular, there are non-ESS states which are significant for evolutionary dynamics. (shrink)

‘Contingent Valuation ’ is a method often used to make decisions about environmental issues. It is used to elicit citizens’ preferences at the location of a specific facility, new road and the like. I argue that even if we could elicit a truly informed and ‘free’ choice, the method would remain flawed, as 1) all ‘local’ activity also has far-reaching environmental consequences; 2) majority decisions may support chices that adversely affect minorities; 3) even with full information, consenting to harms like (...) significant alterations of our normal functioning or health, or genetic mutations, may not be morally acceptable. (shrink)

The mammalian placenta exhibits elevated expression of endogenous retroviruses (ERVs), but the evolutionary significance of this feature remains unclear. I propose that ERV‐mediated regulatory evolution was, and continues to be, an important mechanism underlying the evolution of placental development. Many recent studies have focused on the co‐option of ERV‐derived genes for specific functional adaptations in the placenta. However, the co‐option of ERV‐derived regulatory elements could potentially lead to the incorporation of entire gene regulatory networks, which, I argue, would facilitate (...) relatively rapid developmental evolution of the placenta. I suggest a model in which an ancient retroviral infection led to the establishment of the ancestral placental developmental gene network through the co‐option of ERV‐derived regulatory elements. Consequently, placental development would require elevated tolerance to ERV activity. This in turn would expose a continuous stream of novel ERV mutations that may have catalyzed the developmental diversification of the mammalian placenta. (shrink)

Contemporary political theory is characterised by a realistic critique of liberalism. Realist theorising is seen as avoiding foundational disagreements about justice mutating into second-order disputes concerning the justifiability of legitimate political institutions. In this sense, the realist critique challenges a key aspect of Rawls’ liberal project – that is, its justificatory constituency. McCabe’s Modus Vivendi Liberalism presents an interesting case of such a critique. Given the condition of deep pluralism that characterizes contemporary democracies, the liberal Justificatory Requirement (JR) should be (...) recast so to include those, illiberal or sceptical, who are excluded by Rawls’ justificatory constituency. This paper confronts McCabe’s modus vivendi justificatory project with Rawls view. It suggests that both views seem to endorse a practice-dependent account of political justice in which “politics is prior to morality”; yet the ways in which reasons are endorsed to justify the shared conception of political authority are significantly different in these two schemes. The paper shows that the most problematic aspect of McCabe contingent model is that it disconnects the idea of legitimacy from a conception of liberal political morality. On this account, political legitimacy that reflects the uncoercive character of extant institutions seems to be sufficient to meet the MVL JR. Yet, from a normative point of view, this might be not enough to ensure morally acceptable outcomes. In conclusion, the paper considers McCabe’s model as a version of ‘practice-independent’ moral theorizing committed to a transcendent view of ‘threshold morality’. This move, however, comes at the cost of sacrificing the theory’s premises of anti-perfectionism and realism. (shrink)

This essay introduces and critically explores a theme for philosophical discussion which has almost entirely disappeared from contemporary researches in philosophy, but which used to be a central part of mainstream philosophical debate: the philosophy of the history of the world. At the height of its most intensive period of study in the eighteenth and early nineteenth centuries, philosophical accounts in this area were predominantly theological histories of man. In our time these accounts have been largely displaced by natural histories (...) of man. The change involved in this displacement is not, I contend, a minor shift in philosophical fashion but marks a fundamental mutation in the default construal of the world and the significance of our lives. The naturalization of our understanding of human life is closely tied up with the movement of secularization in European society. However, it is argued that the mutation in the movement of the history of the world that is making itself visible in our time is not best understood as an atheist event but a mutation within a fundamentally Christian one. (shrink)

Natural selection is the populational process whereby, for instance, the relative number of a variant better suited to a given environment’s attributes increases over generations. In other words, a population’s makeup is altered, over generations, to suit the requirements of a particular environment. Niche construction is the process whereby an environment’s attributes can be stably modified by organisms, over generations, to suit requirements of those organisms. Should the latter process, when it occurs, be considered as significant for the complementary fit (...) between organism and environment as the former? According to mainstream evolutionary theory, random genetic mutation is the only source of novel, unlearned, trans-generationally persistent behavior. A growing number of biologists and philosophers of science, however, maintain that organisms are capable of generating such behavior, in response to, for instance, trans-generationally persistent environmental change, by way of phenotype-mediated, developmentally plastic mechanisms that do not require mutation. Should mechanisms of this sort be more generally recognized as the source of the selectable variation that selection operates on? Niche construction theory answers “yes” to both these questions, and the result is a debate over the comprehensiveness of mainstream evolutionary theory. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Lumps and Bumps”Katherine Arens (bio)“Lumps and Bumps” offers a fresh look at nosological classifications in terms of their genesis in eighteenth-century philosophy by acknowledging the proximity of philosophy to the sciences of the mind in the eighteenth and nineteenth centuries, especially in Germany. Today, strict borders are drawn between these fields by mainstream practitioners, but work like Radden’s makes a strong case for acknowledging not only multiculturalism, (...) but also the historicity of science. As such, it is exemplary interdisciplinary work tracing a set of concepts (here, a taxonomy of mental illness) back to its sources. Yet Radden tacitly raises other questions significant for the interrelationships between psychology/psychiatry and philosophy in the nineteenth and twentieth centuries.First, Radden quite rightly points to the fact that taxonomies defining mental illness will differ across cultures (e.g., that Scottish and German “faculty psychologies” differed). Yet her question can be inverted to ask a historical question: how can taxonomies of mental illness be used to interrogate the very construct of “the European Enlightenment” itself (in a sense, offering a variant on Michel Foucault’s Birth of a Clinic). This question is significant, since the “Enlightenment” has an internationalist contour in the history of philosophy that it may well not have had in medicine.In what way, for example, can Hume and Locke be considered more direct references for Kant than his philosophical nemesis, Johann Gottfried Herder, or physiologists La Mettrie (French) and Albrecht von Haller (Swiss)? Today, these two questions seem to lie on opposite sides of acknowledged disciplinary boundaries, across discourses of the various sciences, and they are not generally asked by intellectual historians, since they lie in different cultural traditions. Yet the German Idealist tradition that came out of the Enlightenment in the generation between Wolf and Kant had different boundaries between philosophy and the natural sciences than did its English equivalent. In this sense, then, Radden has made an argument that could be used to indicate how far the British empiricists actually influenced Kant, as an index of how science crosses both disciplinary and national boundaries.Second, Radden’s work raises a methodological issue for interdisciplinary work on the emergence of psychology: how one can trace the rapid mutation of critical terminology within the evolution of a single discipline across time. Even if some differentiation between affect and cognition was in place from the time of Kant all the way through to the DSM, for instance, the historical and cultural behavioral phenomena to which that distinction refers need to be specified in each context in which they occur, in different [End Page 15] times and places. Psychology between Kant and Kraepelin exemplifies this “interdisciplinarity” of an evolving field. Was psychology to be institutionalized as part of philosophy departments, or of physiology, or of education? The research in these three fields was carried out in almost identical terms in the early nineteenth century, but what that research means needs to be further historicized.For example, “reason” and “passion” occur as reference concepts in Goethe’s Sorrows of Young Werther, just as they do in Rousseau’s Nouvelle Heloise and Confessions, and in Richardson’s Pamela. Yet the behaviors that are identified as “passionate” differ across cultures, and so need to be defined today in ways that acknowledge chains of influence as they existed at that time, not as reconstructed for other purposes.The third issue raised by Radden’s study and needing further study is the question of power politics in science. Each use of terms has its own strategic importance, and every act of classification is potentially political. When classification schema are exported, imported, rejected, or upheld, the practitioner/professional not only makes a scientific statement, but a social one as well, by adhering to a set of professional organizations, institutions, and other power configurations in which the schema appear. In the case of Kant’s taxonomy of mind, one might ask what the significance was when he added “will” to the reason/passion dichotomy that pervaded his sources. What has he gained or lost by using these terms in the context of faculty psychology?Similarly, what is the cultural significance of that third... (shrink)

Euglenids comprise a group of single‐celled eukaryotes with diverse modes of nutrition, including phagotrophy and photosynthesis. The level of morphological diversity present in this group provides an excellent system for demonstrating evolutionary transformations in morphological characters. This diversity also provides compelling evidence for major events in eukaryote evolution, such as the punctuated effects of secondary endosymbiosis and mutations in underlying developmental mechanisms. In this essay, we synthesize evidence for the origin, adaptive significance and diversification of the euglenid cytoskeleton, especially (...) pellicle ultrastructure, pellicle surface patterns, pellicle strip number and the feeding apparatus. We also highlight holes in our knowledge that must be filled before we are able to confidently describe euglenid cell biology and infer the earliest stages in euglenid evolution. Nonetheless, by possessing combinations of characters resulting from adaptive change and morphostasis, euglenids have retained key pieces of evidence necessary for reconstructing the early evolution and diversification of eukaryotic life. BioEssays 29:987–1000, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Central to Watts and Newson’s argument in their seminal paper ‘ Is there a duty to routinely reinterpret genomic variant classifications? ’ is that diagnostic laboratories are not morally obligated to actively reinterpret variants of uncertain significance (VUS) due to the superior outcomes offered by next-generation sequencing (NGS) compared with traditional methods.1 NGS technologies can identify, analyse and interpret millions of genetic variations at once. For example, ‘the use of conventional molecular assays in clinical contexts could require doing a (...) lot of assays for various mutations. Using these different assays, more tissue may be required. These targets can accurately be questioned using NGS technology in a single test.’2 If NGS-based genomic sequencing is reliable and its output outweighs the potential harm of uncertainties, then, it is plausible to say that those test providers cannot incur a moral duty to actively reinterpret VUS because there won’t be any need to do so.1 Despite its seeming reliability, diagnostic laboratories face enormous challenges in implementing NGS-based …. (shrink)

In this interview with Yann Moulier Boutang and Carlo Vercellone, André Gorz elaborates on three crucial points of his analysis of the significance of the mutation inherent in the concept of cognitive capitalism: first, the redefinition of the mechanisms of exploitation and the processes of emancipation, since when labor is no longer measurable in units of time, and when self-exploitation takes on a central function in the process of valorization, the production of subjectivity becomes a central site of (...) conflicts; second the importance of snaking a precise distinction between the notion of knowledge, which is objective and formalizable by essence, and the notion of « know-how » or intellectual capability, which is by essence something alive and experienced; third the subjective and objective reasons why cognitive capitalism appears as a crisis of capitalism, containing the seed of another model of society. (shrink)

During the last decades evolutionary science has made significance progress in the elucidation of the process of human evolution and especially of human behavioral characteristics. These themes were traditionally subjects of inquiry in philosophy and theology. Already Darwin suggested an evolutionary and biological basis for moral sense or conscience, and answered Kant’s question about the origin of the moral rules postulated by philosophers. This article reviews the current status of such investigations by natural scientists, biologists and psychologists, and compares (...) their models for explanation of human moral behavior with those postulated by philosophers. Today natural scientists postulate cooperation as the third element of evolutionary process after mutations and natural selection. They seem to fully confirm the intuition of philosophers. The thesis on the fundamental status of cooperation in the entire animal world leads to a belief concerning dialogue: dialogue, rooted in a sense in cooperation, is a primary men’s capability, being emerged from the biological essence of humans. Thus the examination of cooperation reveals inter alia biological foundations of dialogue. (shrink)

Current debate and policy surrounding the use of genetic editing in humans often relies on a binary distinction between therapy and human enhancement. In this paper, we argue that this dichotomy fails to take into account perhaps the most significant potential uses of CRISPR-Cas9 gene editing in humans. We argue that genetic treatment of sporadic Alzheimer’s disease, breast- and ovarian-cancer causing BRCA1/2 mutations and the introduction of HIV resistance in humans should be considered within a new category of genetic protection (...) treatments. We find that if this category is not introduced, life-altering research might be unnecessarily limited by current or future policy. Otherwise ad hoc decisions might be made, which introduce a risk of unforeseen moral costs, and might overlook or fail to address some important opportunities. (shrink)