Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of β-catenin. There are two pools of β-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of β-catenin. Upon Wnt (...) signalling, β-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, β-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311–318, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

During development of the Xenopus embryo, the formation of the nervous system depends on an inductive interaction between mesoderm and ectoderm. The result is a neural tube that is regionally differentiated along the anterior–posterior axis from forebrain to spinal cord (Fig. 1). The discovery of genes whose transcripts can be used as molecular markers for different regions of the nervous system has permitted reassessment of the existing theories of neural tissue formation. Although the neural inducing molecules remain elusive, the mechanism (...) by which cells interact to form a regionally differentiated nervous system is becoming clearer. (shrink)

Pithy, direct, and bold: essays that propose new ways to think about old problems, spanning a range of philosophical topics. In Philosophical Provocations, Colin McGinn offers a series of short, sharp essays that take on philosophical problems ranging from the concept of mind to paradox, altruism, and the relation between God and the Devil. Avoiding the usual scholarly apparatus and embracing a blunt pithiness, McGinn aims to achieve as much as possible in as short a space as possible while (...) covering as many topics as possible. Much academic philosophical writing today is long, leaden, citation heavy, dense with qualifications, and painful to read. The essays in Philosophical Provocations are short, direct, and engaging, often challenging philosophical orthodoxy as they consider issues in mind, language, knowledge, metaphysics, biology, ethics, and religion. McGinn is looking for new ways to think about old problems. Thus he writes, about consciousness, “I think we have been all wrong,” and goes on to suggest that both consciousness and the unconscious are mysteries. Summing up his proposal on altruism, he remarks, “My suggestion can now be stated, somewhat brutally, as follows: human altruism is the result of parasitic manipulation.” He takes a moment to reflect: “I really don't know why it is good to be alive, though I am convinced that the standard suggestions don't work.” McGinn gets straight to the point and states his position with maximum clarity. These essays offer provocative invitations to think again. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:SACRIFICE AND THE PUBLIC SPHERE Colin Jager University ofMichigan The Inscription on the Memorial to Irish Freedom in Parnell Square, Dublin, reads: "O generations of freedom, remember us, the generations of the vision." The irony, of course, is that the generations of freedom to whom the inscription is addressed have yet to be born. Or rather: they/we are partly a generation of freedom, while remaining also and of (...) necessity a generation of vision. Freedom—always partial and imperfect where it exists at all—remains bound up with vision. And violence (so the memorial tells us) is never far from vision. Is itpossible to conceive ofa public sphere free from violence? This is the question I address here with the help ofHannah Arendt. I begin by describing Arendt's distinction between the public and private realms and summarizing Seyla Benhabib's interpretation ofthese categories. Arendt, ofcourse, valued the public sphere ofcontestation that she associated with the Greek world; for her, the private realm of the household should remain completely separate from public life—the private was a place ofmere necessity, devoted solely to maintaining the physical body. According to Benhabib, we can follow Arendt in thinking of the public sphere as a place of contestation and hence of potential pain, or we can allow the concerns of the private into the public realm, and thus work to create a public sphere based on association and potential solidarity. Working out of the communicative theories of Jürgen Habermas, Benhabib tries to pull Arendt toward Habermas by emphasizing what she calls Arendt's "reluctant modernism": those elements ofher thought that move away from a sharp distinction between public and private and tend toward association and solidarity. And yet—this is the conviction that motivates this essay—history tells us that we cannot simply exchange one for the other. The poignancy ofmy epigraph springs, I think, precisely from our 58Colin Jager realization that vision never modulates easily into freedom. The monument's inscription, the very fact of its existence, links vision indissolubly with bloodshed and sacrifice, while imagining freedom as a peaceful realm beyond violence, a place ofharmony and solidarity for which the "generations ofthe vision" were willing to sacrifice themselves. Yet we are not that generation of freedom. We have not shed the burden of vision and history, for history is never simply behind us. What the eighty bloody years since the Easter uprising have taught us, if anything, is that the coming offreedom is always delayed and that the hopes for a peaceful transition from vision to freedom, agon to association, revolution to democracy, are forever marred by the reality ofa world where there is more than one vision and where continued sacrifices in the name ofvision seem to bring us no closer to peace, or to freedom. Who is the monument for, then? We must conclude that it is for us who remain somewhere between vision and freedom, forced by our own monuments to acknowledge that history that continues to infect our present. If agon and association, vision and freedom, inevitably bleed into each other, then we cannot talk realistically about one simply replacing the other. In this regard Arendt's work is crucial because it teaches us that movement from an agonistic Greek public to an associative modern public is accomplished only at the cost of displacing the distributive violence of the Greek world onto a figure ofsuffering. The necessity ofsuch suffering is the element that Benhabib, with her emphasis on the ideal communicative community, misses. Therefore, highlighting suffering helps us to understand Arendt: the suffering figures scattered through her work are the only way to make sense of her crucial notions of storytelling and forgiveness. More generally, highlighting suffering helps us understand what is at stake in any Utopian theory of the public sphere: envisioning the transition from an agonistic public sphere, defined by its relationship to violence, to a nonviolent associative public sphere of peace and communicative ethics is impossible wiüiout acknowledging those who pay the price for such a passage. Freedom, ifit does come, comes at a terrific cost—and there is no guarantee that it will still be here tomorrow. 1. Agonism and Associationism... (shrink)

Mary Astell (1666-1731) relies on a Cartesian account of the self to argue that both men and women are essentially thinking things and, hence, that both should perfect their minds or intellects. In offering such an account of the self, Astell might seem to ignore the inescapable fact that we have bodies. I argue that Astell accommodates the self’s embodiment along two main dimensions. First, she tempers her sharp distinction between mind and body by insisting on their union. The mind (...) and body are united in such a way that they exert reciprocal causal influence and form a whole together. Second, she argues that the mind-body union is good, that the union has its own distinctive form of good or perfection, and that the mind should pursue this good alongside its own. (shrink)

(forthcoming) Journal of Medical Licensure and Discipline. Rapid advances in human genetics raise the prospect that one day we may be able to develop genetic enhancements to promote a diverse range of phenotypes (e.g. health, intelligence, behaviour, etc.). Perhaps the biggest challenge that genetic enhancements pose for medical practitioners is that they will compel us to re-think a good deal of the conventional wisdom of the status quo. Radical enhancements are likely to have this affect for a variety of reasons. (...) Firstly, the status quo is premised (at least in large part) on a sharp distinction between treatment and enhancement; a distinction that at least some genetic enhancements will call into question. Secondly, the prospect of radical enhancements requires us to keep an open mind concerning how we conceive of the harm of non-intervention (i.e. the harm of the status quo). And thirdly, some enhancements might compromise the preservation of personal identity. All of these issues may have important consequences for State Medical Boards, ranging from the way we view the aspiration to prevent harm and ensure reasonable standards of care, to malpractice, continuing competency and medical specialization. (shrink)

Animalism is the view that human persons are human animals – biological organisms that belong to the species Homo sapiens. This paper concerns a family of modal objections to animalism based on the essentiality of personhood (persons and animals differ in their persistence conditions; psychological considerations are relevant for the persistence of persons, but not animals; persons, but not animals, are essentially psychological beings). Such arguments are typically used to support constitutionalism, animalism’s main neo-Lockean rival. The problem with such arguments (...) is that they wrongly assume that animalism is incompatible with our essentially being psychological beings. In this paper, I discuss a formulation of animalism, what I call psychologically-serious animalism, according to which human persons are essentially human animals and essentially persons. I show how the availability of this neglected formulation of animalism undermines objections based on the essentiality of personhood. (shrink)

In Part 1, we situate Dugin’s interpretation of Heidegger in relation to the better known, broadly left-liberal approaches to interpreting Heidegger’s thought, stressing Dugin’s unusual focus on the German thinker’s “middle” or Nazi-era texts, and showing how this periodizing optic affects Dugin’s culminating reading of Sein und Zeit and its key axiological notion of authenticity (Part 1). Part 2 examines Dugin’s appropriation of Heidegger’s radically pessimistic, trans-epochal critique of Western thought, centring around his striking reading of the esoteric notion of (...) the “fourfold” or Gewiert. In this account, the essence of reality itself, the “crosshairs” of the fourfold, is provocatively depicted by Dugin as war, Polemos, Kampf, or Krieg, following the Heidegger of 1933–1936. In a move which echoes Heidegger’s own post-1938 relativizations of all distinctions between Nazism, liberalism and socialism – as well as the Shoah and mechanized agriculture – the Russian thinker hence ends by obviating any distinctions between liberal or democratic and totalitarian regimes, war and peace, and genocide and consumerism. All must be overcome in the “another beginning” destined for the new Russia, if it has the ears to hear. (shrink)

Much of the sustained attention on pandemic preparedness has focused on the ethical justification for plans for the “crisis” phase of a surge when, despite augmentation efforts, the demand for life...

Albert Camus repeatedly denied the label “existentialist,” and pointed to his formative experiences of natural beauty and his early introduction to classical Greek thought and culture as determinative of his philosophy. Pierre Hadot, famous for his post-1970 work on philosophy as a way of life in classical antiquity, continued throughout his life to work on the history of Western conceptions of nature. In Le voile d’Isis, Hadot excavated a second strain of Western attitudes towards nature, alongside the instrumental or “Promethean” (...) approach dominant in modernity: this is that of the contemplative Orphic perspective, closely tied in antiquity to philosophical regimens of spiritual exercises to transform philosophers’ ways of seeing. This paper will argue that Camus and Hadot should be read as two twentieth century “Orphic” figures in this sense, in a way that at once singles them out against almost all other European contemporaries, as well as speaking to our ecological concerns today. Yet the only comparative piece on the two thinkers to date, by Matthew Lamb, misses this shared contemplative, Orphic core to their positions. This paper aims to redress this shortcoming in the reception of the two figures. (shrink)

Albert Camus can be meaningfully read as an agent-focussed virtue ethicist, as David Sherman has suggested. Yet moving far beyond Sherman’s version of this claim, we show here how Camus accepts what are four definitive parameters of the classical authors’ conception of the virtues—the last of which takes him beyond today’s recognised “virtue ethicists.” Firstly, he understands the virtues as lasting, beneficent dispositions to think, feel, and act in certain ways. Secondly, he conceives the virtues as mastering the untethered passions: (...) the sources of epistemic partiality and behavioural excess. Thirdly Camus conceives of the virtues as necessary accomplishments if people are to live fulfilled lives. Finally—and here bidding farewell to a solely theoretical approach—Camus appreciates that such self-mastery can only be achieved through education and habituation, and through the imitation of the kind of exemplars he holds up before us in his literary fiction. (shrink)

This article challenges John M. Cooper’s reading of ancient Stoicism as a way of life, one which sets its back against Pierre Hadot’s notion that Stoicism could have philosophically advocated regimens of non-cognitive practices of the kind documented by Hadot. Part 1 examines Arrian’s Discourses, following A. A. Long in seeing in this text Arrian’s portrait of Epictetus as a philosophical persona: one bringing together the different virtues of Socrates, Diogenes, and Zeno. Part 2 then examines Epictetus’s Handbook , seeing (...) in this text—in contrast to Hadot and Sellars—a distinct set of prescriptions for the kinds of existential practices the Roman Stoics advocated, not in place of philosophical argumentation, but as a means to habituate aspirants’ conduct to ways of thinking, desiring and acting harmonious with their philosophical conclusions. (shrink)

Who, if I cried out, would hear me among the Angelic Orders? And even if one were to suddenly take me to its heart, I would vanish into its stronger existence. For beauty is nothing but the beginning of terror, that we are still able to bear, and we revere it so, because it calmly disdains to destroy us...."So what are you telling me, there's no God, but there's you?"Peter Weir's film Fearless appeared in 1993 to critical acclaim and middling (...) box office fortune. The film draws on all of Weir's considerable art, a stunning sound track, and powerful performances by Jeff Bridges, Rosie Perez, and Isabella Rossellini. Based on the... (shrink)

I argue that David Oelhoffen's 2014 film Far From Men, while departing from the letter of Camus' 1957 story, “The Guest/Host”, does remarkable cinematic justice to its spirit. Oelhoffen's Daru and the Arab character Mohamed, it is suggested, represent embodiments of Camus’ idealised Algerian “first men”, in the vision Camus was developing in Le Premier Homme at the time of his death in January 1960. Part 1 frames the film in light of Camus’ “The Guest/Host”, and Part 2 frames Camus’ (...) story in light of Camus’ agnonised struggle to come to terms with the Algerian situation. Part 3 makes the case that Oelhoffen's departures from Camus’ original story present in cinematic form Camus’ ideal of a post-colonial, post-ethnic solidarity between people, predicated on the overcoming of all arche-ideological fantasies of untained prelapsarian community. (shrink)

ABSTRACTThis article claims that today’s reading of Francis Bacon’s Essayes as a solely literary text turns upon philosophers’ having largely lost access to the renaissance culture which Bacon inherited, and the renaissance debates about the role of rhetoric in philosophy in which Bacon participated. The article has two parts. Building upon Ronald Cranes’ seminal contribution on the place of the Essayes in Bacon’s ‘great instauration’, Part 1 examines how the subjects of Bacon’s Essayes need to be understood as Baconian contributions (...) to ‘morrall philosophye’ and ‘civile knowledge’, rather than rhetorical or poetic exercises. In Part 2, contesting the interpretations of Crane, Fish, Ferrari and others, I will argue that the Essayes’ striking rhetorical form needs to be conceptualized in light of Bacon’s renaissance account of the ‘duty and office’ of rhetoric in any moral and civil philosophy that would look to actively cure mental afflictions and cultivate the virtuous or canny conduct it extols. Bacon’s Essayes, in this light, are best understood as a legatee and transformation of the popular early modern genre of books of apothegms and maxims designed to guide conduct. (shrink)

john c. briggs has commented that "The reading of Baconian texts resembles the Baconian reading of nature, for in both the interpreter must discover a clue to the labyrinth."1 This thought certainly applies to the Praerogatiuis Instantiarum and their precise role in Bacon's Novum Organum.2 These instances occupy thirty-one of the fifty-two sections of Novum Organum II, whereas only nine are devoted to the much better-known work of the tabulation of affirmative, negative and deviating instances, and one long section on (...) the "first vintage" of eliminative induction. The sections on the prerogative instances fill some 131 of the 183 pages of Novum Organum II... (shrink)

Unlike the overall framework of Ernest Nagel's work on reduction, his theory of intertheoretic connection still has life in it. It handles aptly cases where reduction requires complex representation of a target domain. Abandoning his formulation as too liberal was a mistake. Arguments that it is too liberal at best touch only Nagel's deductivist theory of explanation, not his condition of connectability. Taking this condition seriously gives a powerful view of reduction, but one which requires us to index explanatory power (...) to sciences as they are formulated at particular times. While we may thereby reduce more than philosophers have supposed, we must abandon hope (as Nagel did) of saying anything useful about reductionism. (shrink)

Following up on a 1989 paper on the subject, this essay revisits the question of ethical expertise in the court room. Informed by recent developments in the use of ethics experts, the authors argue 1) that the adversarial nature of court proceedings challenges the integrity of the ethicist's pedagogical role; 2) that the use of ethics experts as normative authorities remains dubious; 3) that clarification of the State's interest in “protecting the ethical integrity of the medical profession” is urgently required; (...) and 4) that the expertise of the ethicist may be more appropriately used in advising the legislature than in influencing the court. (shrink)

This short book is intended to be read in an evening or even a sitting, though it provokes reflections that will go on for far longer. Professor Sharpe is a philosopher and writes as a post-Christian. He does not believe in God for moral reasons and argues that in some ways morality is corrupted by religion.

In Zizek and Politics, Geoff Boucher and Matthew Sharpe go beyond standard introductions to spell out a new approach to reading Zizek, one that can be highly critical as well as deeply appreciative. They show that Zizek has a raft of fundamental positions that enable his theoretical positions to be put to work on practical problems. Explaining these positions with clear examples, they outline why Zizek's confrontation with thinkers such as Derrida, Foucault and Deleuze has so radically changed how (...) we think about society. They then go on to track Zizek's own intellectual development during the last twenty years, as he has grappled with theoretical problems and the political climate of the War on Terror. This book is a major addition to the literature on Zizek and a crucial critical introduction to his thought. (shrink)

Although features of the dentition figure prominently in discussions of early hominid phylogeny, remarkably little is known of the developmental basis of the variations in occlusal morphology and dental proportions that are observed among taxa. Recent experiments on tooth development in mice have identified some of the genes involved in dental patterning and the control of tooth specification. These findings provide valuable new insight into dental evolution and underscore the strong developmental links that exist among the teeth and the jaws (...) and cranium. The latter has important implications for cladistic studies that traditionally consider features of the skull independently from the dentition. BioEssays 23:481–493, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The cause of Paget's disease is still unknown, despite many years of intensive study. During this time, evidence has sporadically emerged to suggest that the disease may result from a slow viral infection by one or more of the Paramyxoviruses. More recently, epidemiologic and molecular studies have suggested that the canine paramyxovirus, canine distemper virus, is the virus responsible for the disease. If true, then along with rabies, this would be a further example of a canine virus causing human disease. (...) Studies in the natural host have now supported these findings. Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin‐6 and c‐FOS production, possibly via the transcription factor NF‐kB. (shrink)

This inquiry is situated at the intersection of two enigmas. The first is the enigma of the status of Kant's practice of critique, which has been the subject of heated debate since shortly after the publication of the first edition of The Critique of Pure Reason. The second enigma is that of Foucault's apparent later 'turn' to Kant, and the label of 'critique', to describe his own theoretical practice. I argue that Kant's practice of 'critique' should be read, after Foucault, (...) as a distinctly modern practice in the care of the self, governed by Kant's famous rubric of the 'primacy of practical reason'. In this way, too, Foucault's later interest in Kant - one which in fact takes up a line present in his work from his complementary thesis on Kant's Anthropology - is cast into distinct relief. Against Habermas and others, I propose that this interest does not represent any 'break' or 'turn' in Foucault's work. In line with Foucault's repeated denials that he was interested after 1976 in a 'return to the ancients', I argue that Foucault's writings on critique represent instead both a deepening theoretical self-consciousness, and part of his project to forge an ethics adequate to the historical present.
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The Great War, as it was known until 1939, set in chain a series of catastrophes and crises that have largely defined the long twentieth century: economic, political, cultural, and metaphysical. Philosophy was not unaffected, either within academe, or more widely. Nearly each of the major philosophical movements, from analytic philosophy through to post-structuralism, was directly or indirectly formed in response to the civilizational crisis the Great War inaugurated, and different perceptions of its causes and significance. This chapter surveys the (...) territory, and looks forwards to the different contributions collected here. (shrink)

: The revival of philosophical pragmatism has generated a wealth of intramural debates between neopragmatists like Richard Rorty and contemporary scholars devoted to explicating the classical pragmatism of John Dewey and William James. Of all these internecine conflicts, the most divisive concerns the status of language and experience in pragmatist philosophy. Contemporary scholars of classical pragmatism defend experience as the heart of pragmatism while neopragmatists drop the concept of experience in favor of a thoroughly linguistic pragmatism. I argue that both (...) positions engender formidable risks. After discussing the present impasse, I describe a third version of pragmatism which involves a reconstruction of the classical pragmatist concept of experience in light of the criticisms of foundationalism crucial to the neopragmatist linguistic turn. This third version of pragmatism does justice to both Rorty and Dewey by focusing on experience as a temporal field. (shrink)

The laboratory creation scene in Branagh’s film is brilliant….Even more frenzied and overwrought than Whale’s, Branagh’s creation scene is filmed with dozens of quick cuts, each shot full of movement across the frame. Victor races along his attic hall, cape flying before he discards it to appear bare-chested and vigorous. While pulleys move, bottles clank, and blue volts of electricity rise in glass Tesla tubes, the naked body on the gurney is raised into a copper vat. Electric eels dispense their (...) powerful shocks, a brown sac-like bellows "breathes" air or heat, and finally Victor stares close-up at the Creature’s eyes. The eyes are seen through a porthole in the vat: this, our first glimpse of the monster occurs nearly an hour into the film. "Live, live, live, live...." Victor chants, then "YES!" (much in the old Colin Clive mode) as it opens its eyes briefly. Nothing more occurs, though, and Victor walks away in despair; but, like us, he is brought suddenly to attention by a sharp and surprising snap of the monster’s fingers, which we also see close-up through a porthole (in a clear allusion to the Karloff monster’s birth scene). The next sequence drives home the fact that this is a real birth scene, as the vat is smashed open (the "water breaks") and Victor lifts out his huge new "baby," smacking its chest to clear its lungs. We watch an extended scene of birth struggle while Victor works to "deliver" his huge, naked, and hairless "baby" by lifting it out of the slime. Giving birth is not only very hard labor here; it’s messy, too. (shrink)

Nanotechnology thrives in the realm of the virtual. Throughout its history, the field has been shaped by futuristic visions of technological revolution, hyperbolic promises of scientific convergence at the molecular scale, and science fiction stories of the world rebuilt atom by atom. Even today, amid the welter of innovative nanomaterials that increasingly appear in everyday consumer products—the nanoparticles enhancing our sunscreens, the carbon nanotubes strengthening our tennis rackets, the antimicrobial nano-silver lining our socks, the nanofilms protecting our wrinkle-free trousers—the public (...) rhetoric of nanotechnology constantly reminds us that such precision-engineered materials merely represent a trace or a premonition of the amazing future still to come... (shrink)

The recent success of the Mars 2020 project and the high quality images relayed back to Earth have provided further impetus and expectations for human missions to Mars. To support space agency and private enterprise plans to establish a sustainable colony on Mars in the 2030s, synthetic biology may play a vital role to enable astronaut self-sufficiency. In this review, we describe some aspects of where synthetic biology may inform and guide in situ resource utilisation strategies. We address the nature (...) of Martian regolith and describe methods by which it may be rendered fit for purpose to support growth and yield of bioengineered crops. Lastly, we illustrate some examples of innate human adaptation which may confer characteristics desirable in the selection of colonists and with a future looking lens, offer potential targets for human enhancement. (shrink)

As in science, so in bioethics: if prohibiting conflicts of interest is not feasible, rigorous requirements for disclosure can at least manage them.

This study aimed to capture how the coronavirus disease 2019 crisis disrupted and affected individuals’ goal pursuits and self-efficacy beliefs early during the lockdown phase of COVID-19. Participants impacted by lockdown regulations accessed an online questionnaire during a 10-day window from the end of March to early April 2020 and reported a significant personal goal toward which they had been working, and then completed quantitative and qualitative survey items tapping self-efficacy beliefs for goal achievement, subjective caring about the goal during (...) disrupted world events, and current pursuit or abandonment of the goal. The findings from both quantitative and qualitative measures demonstrated a significant drop in self-efficacy beliefs from before to during the pandemic with a large effect based on whether people thought they could still achieve their goal under current conditions. Over two-thirds of the sample was unsure or did not believe they could still carry out their goal, and over a quarter either abandoned or were uncertain they could pursue the goal. Despite this, people continued to care about their goals. Reasons for abandonment and strategies for coping with goals within the lockdown and beyond are discussed. (shrink)

ABSTRACTOscar Larsson’s sympathetic critique of constructivist institutionalism calls for a clarification of my understanding of subjectivity, inter-subjectivity, and their mutual interdependence. That interdependence lies at the heart of any genuinely constructivist approach, just as the interdependence of structure and agency lies at the heart of any genuinely institutionalist approach. As such, I reject the charge of subjectivism just as I would that of voluntarism. Building on the social ontology of Berger and Luckmann, we can distinguish between subjectivity and intra-subjectivity and (...) proceed to show how the latter implies a notion of inter-subjectivity. An example of the social construction of a political crisis shows that social facts are made and remade through a fusion of inter- and intra-subjectivities. (shrink)