Hedgehog is an important morphogenic signal that directs pattern formation during embryogenesis, but its activity also remains present through adult life. It is now becoming increasingly clear that during the reproductive phase of life and beyond it continues to direct cell renewal (which is essential to combat the chronic environmental stress to which the body is constantly exposed) and counteracts vascular, osteolytic and sometimes oncological insults to the body. Conversely, down‐regulation of hedgehog signalling is associated with ageing‐related diseases (...) such as type 2 diabetes, neurodegeneration, atherosclerosis and osteoporosis. Hence, in this essay we argue that hedgehog signalling is not only important at the start of life, but also constitutes an important anti‐geriatric influence, and that enhanced understanding of its properties may contribute to developing rational strategies for healthy ageing and prevention of ageing‐related diseases.Also watch the Video Abstract. (shrink)

The Hedgehog, the Fox, and the Magister's Pox is a controversial discourse, rich with facts and observations gathered by one of the most erudite minds of our ...

In a number of papers, including the one published in this journal, Robert Sparrow has mounted attacks on consequentialism using principally what he takes to be an important fact, which he believes constitutes a reductio ad absurdum of consequentialism in its many forms and of this author's approach to enhancement and disability in particular (see page 276). This fact is the current longer life expectancy of women when compared with men. Here the author argues that Sparrow's arguments and entire approach (...) utterly fail. In doing so the author hopes to shed further light on the role of normalcy, normal species functioning and species-typical functioning in debates about enhancement and disability. (shrink)

Perhaps Archilochus simply meant that the hedgehog’s single defense defeats the fox’s many tricks. Yet, the hedgehog and the fox were turned into metaphors for two types of thinkers and writers by the historian philosopher Isaiah Berlin. All the thinking and actions of the hedgehog revolve around a single vision and are structured by a single set of principles that the hedgehog holds to be universal. Foxes lack such central vision and universal principles; they seize many (...) experiences and pursuit many ends, always holding concrete particulars to be paramount. Each way of thinking has its strength and weakness; neither is superior to the other. Berlin cited Plato, Dante, and Dostoevsky as hedgehogs; Aristotle, Shakespeare, and Pushkin foxes. Tolstoy was diagnosed as a fox who imagined himself a hedgehog. (shrink)

Drawing on Isaiah Berlin's celebrated essay on Tolstoy, this paper poses the question should James Turner Johnson be deemed a hedgehog or a fox? That is, it considers whether Johnson should be regarded as a monist (hedgehog) or a pluralist (fox) in his contribution to the just war tradition. It contends that his commitment to history, while superficially indicative of a hedgehog, serves to conceal a deep-lying pluralism ? or at least the possibility of such ? in (...) his views on the meaning of history. Contrary to initial appearances, then, Johnson's commitment to history is not univocal: it does not speak with one voice, and to one purpose. Rather it suggests a variety of voices or positions, and is amenable to multiple interpretations, not all of which are of a piece with one another. This paper seeks to uncover these various voices or positions, with a view to raising some searching questions pertaining to how we should properly understand the just war tradition today. (shrink)

Two posttranslational lipid modifications present on all Hedgehog (Hh) morphogens—an N‐terminal palmitate and a C‐terminal cholesterol—are established and essential regulators of Hh biofunction. Yet, for several decades, the question of exactly how both lipids contribute to Hh signaling remained obscure. Recently, cryogenic electron microscopy revealed different modes by which one or both lipids may contribute directly to Hh binding and signaling to its receptor Patched1 (Ptc). Some of these modes demand that the established release factor Dispatched1 (Disp) extracts dual‐lipidated (...) Hh from the cell surface, and that another known upstream signaling modulator called Scube2 chaperones the dual‐lipidated morphogen to Ptc. By mechanistically and biochemically aligning this concept with established in vivo and recent in vitro findings, this reflection identifies remaining questions in lipidated Hh transport and evaluates additional mechanisms of Disp‐ and Scube2‐regulated release of a second bioactive Hh fraction that has one or both lipids removed. (shrink)

¿The fox knows many things, but the hedgehog knows one big thing.¿ This fragment of Archilochus, which gives this book its title, describes the central thesis of Isaiah Berlin¿s masterly essay on Tolstoy. There have been various interpretations of Archilochus¿ fragment; Isaiah Berlin has simply used it, without implying anything about the true meaning of the words, to outline a fundamental distinction that exists in mankind, between those who are fascinated by the infinite variety of things (foxes) and those (...) who relate everything to a central all-embracing system (hedgehogs). When applied to Tolstoy, the image illuminates a paradox of his philosophy of history, and shows why he was frequently misunderstood by his contemporaries and critics. Tolstoy was by nature a fox, but he believed in being a hedgehog. (shrink)

Embryonic development in a given species is orchestrated by genes regulating growth and differentiation in a stereotyped and conserved manner, resulting in embryos of consistent size and shape. Several signaling pathways, including that of Sonic Hedgehog (SHH), have been implicated in these processes. Recent experiments with Gas1 indicate that it may act as a growth-inducing gene, challenging its previous function as a gene specifically involved in growth arrest. Moreover, GAS1, a GPI-linked membrane protein, can bind SHH, suggesting an interacting (...) link between growth and patterning through SHH and GAS1.(1-4) BioEssays 24:22–26, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

In this commentary, I critically discuss the respective views of Gert and Beauchamp–Childress on the nature of so-called common morality and its promise for enriching ethical reflection within the field of bioethics. Although I endorse Beauchamp and Childress’ shift from an emphasis on ethical theory as the source of moral norms to an emphasis on common morality, I question whether rouging up common morality to make it look like some sort of ultimate and universal foundation for morality, untouched by the (...) dialectics of time and reflective equilibrium, was an equally good move. As for Gert’s magisterial conception of common morality, I conclude that certain elements of his system are controversial at best and woefully inadequate at worst. He has a tendency to find in common morality what he himself put there, and his highly restricted conception of duties of assistance strikes this reader as ad hoc, inadequately defended, and unworthy of a project whose goal is to lessen the amount of misery in the world. (shrink)

In this paper I take Rorty’s self-description as a “hedgehog” as the starting point for a portrait of his intellectual temperament. I re-examine in the first instance Isaiah Berlin’s contrast between hedgehogs and foxes as inspired by the proverb of Archilocus. I then analyze, in philosophical terms, some differences between foxes and hedgehogs. I distinguish different types of hedgehogs in order to make clear exactly what kind of hedgehog Rorty was. In spite of his multiple interests and conversations, (...) I argue, Rorty portrayed himself as a hedgehog with only one important idea: the need to overcome notions such as Truth and Reason and to promote a less cruel and more anti-authoritarian way of living. I claim that this single idea is better understood when we pay special attention as to why Rorty gave priority to literature over philosophy, why he made distinctions between different types of writers, and why one of his favorite writers, Nabokov, was only apparently a fox. (shrink)

Baedeker -- Independence. Truth in morals -- External skepticism -- Morals and causes -- Internal skepticism -- Interpretation. Moral responsibility -- Interpretation in general -- Conceptual interpretation -- Ethics. Dignity -- Free will and responsibility -- Morality. From dignity to morality -- Aid -- Harm -- Obligations -- Politics. Political rights and concepts -- Equality -- Liberty -- Democracy -- Law -- Epilogue. Dignity indivisible.

Hedgehog proteins are of pivotal importance for development and maintenance of tissue patterns in adult organisms. Despite the role of Hedgehogs in differentiation and tumorigenesis, signal transduction of Hedgehog remains a relatively uncharted area of signalling biochemistry. For proper Hedgehog distribution into tissues, two highly unusual covalent modifications are necessary, palmitoylation of a secreted protein and the attachment of a cholesterol group, making Hedgehog the only established sterolated protein in nature. Hedgehog exerts its function via (...) two membrane‐bound receptors, Patched and Smoothened; presumably, Patched transports a cholesterol derivate out of cells which inhibits Smoothened. Binding of Hedgehog to Patched impedes this proposed pump function and thus Inhibition of Smoothened, which leads to expression of genetic Hedgehog targets via relief of transcriptional repression. These atypical features make Hedgehog physiology unique in biology and may explain why this field has attracted such significant attention. BioEssays 26:387–394, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The close link between signaling by the developmental regulators of the Hedgehog family and cholesterol biochemistry has been known for some time. The morphogen is covalently attached to cholesterol in a peculiar autocatalytic reaction and embryonal disruption of cholesterol synthesis leads to malformations that mimic Hh signaling defects. Recently, it was furthermore shown that secreted Hh could hitchhike on lipoprotein particles to establish its morphogenic gradient in the developing embryo. Additionally, there is new evidence that the Hh‐receptor Patched transmits (...) the Hh signal by modulating the secretion of an inhibitory sterol molecule from the receiving cells. Here we present some of the most recent discoveries on the Hh–sterol link and discuss their implications from a systems design perspective. We predict that a robust functioning of the Hh pathway will require the involvement of more sterol metabolites, and these should be the subject of future research. BioEssays 29:1085–1094, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

"The fox knows many things, but the hedgehog knows one big thing." This ancient Greek aphorism, preserved in a fragment from the poet Archilochus, describes the central thesis of Isaiah Berlin's masterly essay on Leo Tolstoy and the philosophy of history, the subject of the epilogue to War and Peace. Although there have been many interpretations of the adage, Berlin uses it to mark a fundamental distinction between human beings who are fascinated by the infinite variety of things and (...) those who relate everything to a central, all-embracing system. Applied to Tolstoy, the saying illuminates a paradox that helps explain his philosophy of history: Tolstoy was a fox, but believed in being a hedgehog. One of Berlin's most celebrated works, this extraordinary essay offers profound insights about Tolstoy, historical understanding, and human psychology. This new edition features a revised text that supplants all previous versions, English translations of the many passages in foreign languages, a new foreword in which Berlin biographer Michael Ignatieff explains the enduring appeal of Berlin's essay, and a new appendix that provides rich context, including excerpts from reviews and Berlin's letters, as well as a startling new interpretation of Archilochus's epigram. (shrink)

The need to provide novel but meaningful ways to reason and talk about an unprecedented crisis such as the Covid-19 pandemic has resulted in a surge of creative metaphoric expressions in a variety...

In his 2011 book Justice for Hedgehogs, Ronald Dworkin makes a case for the view that genuine values cannot conflict and, moreover, that they are necessarily mutually supportive. I argue that by prioritizing coherence over the conceptual authenticity of values, Dworkin’s ‘interpretivist’ view risks neglecting what we care about in these values. I first determine Dworkin’s position on the monism/pluralism debate and identify the scope of his argument, arguing that despite his self-declared monism, he is in fact a pluralist, but (...) unusual in denying conflict between plural values. I then set out the structure of his interpretive theory of value relations and present a case of value conflict which I think interpretivism cannot deal with. Following this I argue that there are structural reasons why cases like this are liable to occur and suggest that interpretivism will frequently fail to properly reflect people’s moral commitments because reinterpretation of values has the side effect of excluding important moral commitments from our conceptions of values. While, as Dworkin argues, there are no brute moral facts concerning values, moral psychology constrains the range of acceptable conceptions of values. Given the shortcomings of interpretivism I conclude that we should acknowledge that values may conflict. (shrink)

The complexity of the Hedgehog (Hh) signaling cascade has increased over the course of evolution; however, it does not suffice to accommodate the dynamic yet robust requirements of differential Hh signaling activity needed for embryonic development and adult homeostatic maintenance. One solution to solve this dilemma is to apply multiple forms of post‐translational modifications (PTMs) to the core Hh signaling components, modulating their abundance, localization, and signaling activity. This review summarizes various forms of protein modifications utilized to regulate Hh (...) signaling, with a special emphasis on crosstalk between different forms of PTMs and their feedback regulation by Hh signaling. (shrink)

Philip E. Tetlock's finding that "hedgehog" experts are worse predictors than "foxes" offers fertile ground for future research. Are experts as likely to exhibit hedgehog- or fox-like tendencies in areas that call for explanatory, diagnostic, and skill-based expertise-as they did when Tetlock called on experts to make predictions? Do particular domains of expertise curtail or encourage different styles of expertise? Can we trace these different styles to childhood? Finally, can we nudge hedgehogs to be more like foxes? Current (...) research can only grope at the answers to these questions, but they are essential to gauging the health of expert political judgment. (shrink)

For those of us who are sympathetic to the research program of cognitive science, it is especially useful to face the deepest and sharpest critic of that program. Charles Taylor, who defines himself as a ‘hedgehog’ whose ‘single rather tightly related agenda’ fits into a very ancient and rather elusive debate between naturalism and anti-naturalism, may well be that critic. My ambition in this paper is to distill Taylor’s central objection to the cognitive science approach to agency and the (...) self as it is expressed throughout Human Agency and Language. After trying to set out the core of this objection, I want to remark on some rather curious aspects of the dispute of which it is a part, and then sketch, in relation to one or two examples, what I take to be the most promising line of resistance to Taylor’s attack. I conclude with a proposal as to how Taylor may – narrowly – escape one logical consequence of his position, according to which he should stop knocking the cognitive science program and instead go to work building a robot. (shrink)

Philip E. Tetlock's finding that "hedgehog" experts (those with one big theory) are worse predictors than "foxes" (those with multiple, less comprehensive theories) offers fertile ground for future research. Are experts as likely to exhibit hedgehog- or fox-like tendencies in areas that call for explanatory, diagnostic, and skill-based expertise-as they did when Tetlock called on experts to make predictions? Do particular domains of expertise curtail or encourage different styles of expertise? Can we trace these different styles to childhood? (...) Finally, can we nudge hedgehogs to be more like foxes? Current research can only grope at the answers to these questions, but they are essential to gauging the health of expert political judgment. (shrink)

For those of us who are sympathetic to the research program of cognitive science, it is especially useful to face the deepest and sharpest critic of that program. Charles Taylor, who defines himself as a ‘hedgehog’ whose ‘single rather tightly related agenda’ fits into a very ancient and rather elusive debate between naturalism and anti-naturalism, may well be that critic. My ambition in this paper is to distill Taylor’s central objection to the cognitive science approach to agency and the (...) self as it is expressed throughout Human Agency and Language. After trying to set out the core of this objection, I want to remark on some rather curious aspects of the dispute of which it is a part, and then sketch, in relation to one or two examples, what I take to be the most promising line of resistance to Taylor’s attack. I conclude with a proposal as to how Taylor may – narrowly – escape one logical consequence of his position, according to which he should stop knocking the cognitive science program and instead go to work building a robot. (shrink)

Hedgehog (Hh) signaling is a widely studied signaling pathway because of its critical roles during development and in cell homeostasis. Vertebrate canonical and non‐canonical Hh signaling are typically assumed to be distinct and occur in different cellular compartments. While research has primarily focused on the canonical form of Hh signaling and its dependency on primary cilia – microtubule‐based signaling hubs – an extensive list of crucial functions mediated by non‐canonical Hh signaling has emerged. Moreover, amounting evidence indicates that canonical (...) and non‐canonical modes of Hh signaling are interlinked, and that they can overlap spatially, and in many cases interact functionally. Here, we discuss some of the many cellular effects of non‐canonical signaling and discuss new evidence indicating inter‐relationships with canonical signaling. We discuss how Smoothened (Smo), a key component of the Hh pathway, might coordinate such diverse downstream effects. Collectively, pursuit of questions such as those proposed here will aid in elucidating the full extent of Smo function in development and advance its use as a target for cancer therapeutics. (shrink)

Hedgehog (HH) signaling is a conserved pathway that drives developmental growth and is essential for the formation of most organs. The expression of HH target genes is regulated by a dual switch mechanism where GLI proteins function as bifunctional transcriptional activators (in the presence of HH signaling) and transcriptional repressors (in the absence of HH signaling). This results in a tight control of GLI target gene expression during rapidly changing levels of pathway activity. It has long been presumed that (...) GLI proteins also repress target genes prior to the initial expression of HH in a given tissue. This idea forms the basis for the limb bud pre‐patterning model for regulating digit number. Recent findings indicate that GLI repressor proteins are indeed present prior to HH signaling but contrary to this model, GLI proteins are inert as they do not regulate transcriptional responses or enhancer chromatin modifications at this time. These findings suggest that GLI transcriptional repressor activity is not a default state as assumed, but is itself regulated in an unknown fashion. We discuss these findings and their implications for understanding pre‐patterning, digit regulation, and HH‐driven disease. (shrink)

According to Ronald Dworkin, political obligation is to be justified as an associative obligation through membership in certain political communities. In this regard, I first argue that the concept of an associative obligation cannot help us to account for precise moral obligations. Second, I analyze certain disanalogies between paradigmatic cases of associative obligation and political obligation in order to show the inability of the former to justify the enforcement of a comprehensive obligation such as the latter. Finally, I argue that (...) Dworkin could not have provided a better argument: His theory of law makes him incapable of justifying political obligation. (shrink)

Among the remains of Archilochus is an iambic trimeter which is as mysterious as it is charming. Zenobius, who quotes it , says that it was written by Homer and used by Archilochus in his Epodes. If he is telling the truth, it must, as Bergk saw, come from the Margites. But its origin and original purpose need not now concern us. The important fact is that Archilochus used it, and we ought to be able to discover how he used (...) it. What was his precise intention when he quoted or composed the line πλλ᾽ οδ᾽ λπη λλ᾽ χνος ν μγα, what was the contrast he drew between the Fox and the Hedgehog, and how did he make use of it? Zenobius gives two aids, but neither is so easy as it looks at first sight. First, he says that the proverb was used π τν πανουργοττων, and secondly he quotes as relevant some lines from the Phoenix of Ion of Chios about the hedgehog: λλ᾽ ν τε χρσ τς λοντος ᾔνεσα ἢ τς χνου μλλον οζυρς τχνας. ς ετ᾽ ν λλων κρεισσνων ρμν μθ, στρβιλος μΦ᾽ κανθαν ελας δμας κεîται δακεν τε κα θιγεν μχανος. (shrink)

Redish et al. provide a significant advance in our understanding of addiction by showing that the various addictive processes are in fact all decision-making processes and each may undergird addiction. We propose means for identifying more central addiction processes. This recognition of the complexity of addiction followed by identification of more central processes would help guide the development of prevention and treatment.

This essay reviews three recently published books on the intellectual history of the Italian Renaissance. In his survey of Italian humanism in the “long fifteenth century” (c. 1350–c. 1525) The Intellectual World of the Italian Renaissance, Christopher Celenza argues that the intellectual project of the humanists was centred on questions regarding language, philosophy, and the stance of the intellectual toward institutions. Celenza traces the fortunes and mutations of the humanist project into the modern era in The Italian Renaissance and the (...) Origins of the Humanities, and expresses concern that in today's universities the balance struck by the humanists between “openness” and “boundary-generating habits” unduly favours the latter. Humanism, according to James Hankins's Virtue Politics, was primarily about repairing politics by first reforming the moral character of Italy's ruling elites. The language and literature of Roman and Greek antiquity provided the models for this education in virtue. Hankins believes the humanists' educational and cultural programme offers a salutary corrective to our misplaced, post-Machiavellian trust in legal constraints and constitutional guardrails to regulate contemporary political life. (shrink)

This article raises some incompatibilist challenges for, and queries some of the implications of, Ronald Dworkin’s arguments in his "Justice for Hedgehogs" (2011), that responsibility is compatible with both determinism and epiphenomenalism.

This article reviews the outstanding and thought-provoking work by Roberta De Monticelli (2021), _Towards a Phenomenological Axiology. Discovering What Matters_. The article addresses the reasons why it should be read by everyone but especially by help professions practitioners. Although we all deal with morality and value judgments on on mundane, everyday bases, the professional life of education and care practitioners is namely a series of morally-loaded practices and decision-making informed by morally oriented (expert) knowledge. Beyond the thesis advanced in the (...) book, its major contribution consists in making the reader think the inescapability of morality in everyday thinking and acting and the need for a reflective positioning towards this issue. By aligning with “the hedgehog vs. the fox” struggle proposed by the author as the framework of her theoretical proposal, the article advances what would be the doubts and counterarguments of a fox-like scholar in education. It illustrates why her “professional vision” cannot but notice what appears to be under-thematized by the hedgehog, i.e., the unavoidable mediation of language and social interaction that _precedes_ and therefore impacts the constitution of what the hedgehog convincingly notices: the entanglement of fact and value. The conclusion is dedicated to the (underestimated?) place of social sciences in such a debate, their tension between implicit normativity and presumed descriptivity, as well the challenges of the increasingly explicit normativity of applied social sciences. (shrink)