Michael Rosen

Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin.

Immunophilins, when complexed to immunosuppressive ligands, appear to inhibit signal transduction pathways that result in exocytosis and transcription. The solution structure of one of these, the human FK506 and rapamycin binding protein (FKBP), has been determined by nuclear magnetic resonance (NMR). FKBP has a previously unobserved antiparallel beta-sheet folding topology that results in a novel loop crossing and produces a large cavity lined by a conserved array of aromatic residues; this cavity serves as the rotamase active site and drug-binding pocket. There are other significant structural features (such as a protruding positively charged loop and an apparently flexible loop) that may be involved in the biological activity of FKBP.

1H and 15N assignments and secondary structure of the Src SH3 domain.

The 1H and 15N sequential assignments of the Src SH3 domain have been determined through a combination of 2D and 3D Nuclear Magnetic Resonance (NMR) methods. The secondary structure of the protein has been identified based on long‐range NOE patterns. The SH3 domain of Src consists largely of six β‐strands that form two anti‐parallel β‐sheets.

Molecular recognition of immunophilins and immunophilin-ligand complexes

Abstract Immunophilin-ligand complexes have been used to identify a previously unknown step in Ca2+-dependent signal transduction pathways. This Report, which we dedicate to Professor Harry H. Wasserman, describes structural and mechanistic aspects of immunophilin research.

On Voluntary Servitude and the Theory of Ideology

In 1996 I published On Voluntary Servitude: False Consciousness and the Theory of Ideology, a book on which I had been working for a number of years. The theory of ideology, as I understood it, seemed to me to be – or, at least, to have been until recently – the dominant response to what is a puzzling but frequently observed feature of political life: namely, that those who are maltreated – oppressed, exploited, even enslaved – do not always reject that treatment. As Wilhelm Reich puts it: “What has to be explained is not the fact that the man who is hungry steals or the fact that the man who is exploited strikes, but why the majority of those who are hungry don’t steal and why the majority of those who are exploited don’t strike.” My argument is that, although the problem identified by Reich is a genuine one, the solution offered by the theory of ideology is fundamentally unsatisfactory. In this article, I propose to present briefly what I take to be On Voluntary Servitude’s main theses and to respond to some of the critical reactions that I have had from readers, either personally or in the form of reviews.

Must we return to moral realism

In this paper I discuss Taylors criticism of contemporary moral philosophy and the role which this plays in his wider account of the development of Western moral consciousness, an account which I compare with Hans Blumenbergs The Legitimacy of the ModernAge. While I endorse Taylors rejection of ‘naturalism’, I deny that this entails the rejection of non‐realism and I maintain that, indeed, the non‐realist conception of a social foundation for morality represents the most cogent response to the contemporary dilemmas Taylor identifies.

THE CONFORMATION OF CYCLOSPORIN A BOUND TO CYCLOPHILIN IS ALTERED (ONCE AGAIN) FOLLOWING BINDING TO CALCINEURIN: AN ANALYSIS OF RECEPTOR-LIGAND-RECEPTOR INTERACTIONS

Analyses of the complexation of cyclosporin A (CsA) by cyclophilin and the unusual properties of MeBmztl-CsA lead us to propose a conformational change upon binding of the cyclophilin-CsA complex to the protein phosphatase, calcineurin. Structural analyses of natural products bound to their protein receptors can provide a detailed understanding of phenomena ranging from enzymatic catalysis to signal transduction. This is especially true when such analy- ses are combined with experimental results from other disciplines such as synthetic chemistry and molecular bi- ology. In fact, it may be argued that the power of structure determination resides primarily in its ability to ex- plain experimental data, and in doing so to facilitate the formulation of hypotheses which then can direct further experiments. In this report we describe a proposed model for the interactions in a multimeric complex involving two proteins and a natural product ligand. The model is based on crystallographic and NMR spectroscopic anal- yses of one of the proteins and its complex with the natural product, and on biochemical and biological data on a synthetic analog of the natural product.

Die Vernunft und das Absolute

Fur den Deutschen Idealismus und die in ihm vollzogene Kritik an der traditionellen Metaphysik, bzw. seine verschiedenen Versuche, sie in neue Formen philosophischer Systembildungen zu transformieren, sind mindestens zwei Vorgange kennzeichnend.

System und Methode

Der in der Philosophie des Deutschen Idealismus vertretene Begriff des Systems lost wohl bei Lesern mit einer eher empirischen Ausrichtung Befremden aus. Allem Anschein nach fuhrt der Wunsch nach einer Systematisierung allen Wissens zu einer unbegrundeten Synthese von Begriffen, bei der eine Berucksichtigung von in den Naturwissenschaften aufzufindenden Rechtfertigungsformen durchweg abgelehnt wird. Eine Philosophie, die durch vorgefaste Vorstellungen einer inneren Systematizitat der Realitat verblufft — mus sie nicht mit einer ebenso fragwurdigen Methodologie operieren? Edmund Husserl bringt dieses konventionelle Vorurteil sarkastisch zum Ausdruck:

Non-Religious Ethics?

The History Workshop was a movement of radical social historians which flourished in Britain in the 1960s and 1970s. Its goal was to promote ‘history from below’ – to tell the stories of those left out of conventional narratives, and, at the same time, to open up the practice of history itself. Anyway, when the group decided to start a journal, there was a debate over whether it should carry book reviews. Weren’t book reviews – the ranking of others’ work, delivered in a tone of apparent omniscience – examples of exactly the kind of academic gate-keeping against which they had set themselves? So, in its early issues at least, the History Workshop Journal didn’t carry reviews but ‘Enthusiasms’ – contributions in which someone would introduce a new book to readers in positive terms, without pretending to be marking it in some transcendental Prize Fellowship Examination. I have always had a lot of sympathy with their point of view and it came back to me with force when I was asked to provide a critical notice of On What Matters. On What Matters is a vast book (it has been said that it is the only work of contemporary moral philosophy that is visible from space) and it challenges its readers in many ways, one of which – admittedly not, perhaps, the most significant – is that it is impossible to review conventionally. Should the reviewer summarize the book? Well, it deals with most of the central questions of normative and meta-ethics. It also offers an extended interpretation of Kant’s moral philosophy and addresses some of the major questions of epistemology and metaphysics for good measure. Even a long critical notice would be hard pressed to go past such simple headlines and slogans if it aimed to give a comprehensive survey. As for assessment, that seems presumptuous. That On What Matters is the major work of a highly respected and influential contemporary author is, surely, obvious. Will it pass ‘the test of time’? My guess is that its size and scope will make On What Matters an unavoidable part of the landscape of moral philosophy for the foreseeable future. How it will be seen, however, International Journal of Philosophical Studies , 2013 Vol. 21, No. 5, 755–772, http://dx.doi.org/10.1080/09672559.2013.857818

Der philosophische Beitrag der deutschen Frühromantik und Hölderlins

›Fruhromantik‹ ist ein geistesgeschichtlicher Ordnungsbegriff, der zur Kennzeichnung einer einflus-reichen Stromung im deutschen Kulturleben Ende des 18. Jahrhunderts verwendet wird. Zur Fruhromantik zahlt zunachst der enge Kreis um die Bruder August Wilhelm (1767–1845) und Friedrich Schlegel (1772–1829) mit ihren Lebensgefahrtinnen Caroline Michaelis (1763–1809), die erst August Wilhelm Schlegel heiratete, spater dann Friedrich Wilhelm Joseph Schelling (1775–1854), und Dorothea Veit (1764–1839), die Tochter Moses Mendelssohns, die mit Friedrich Schlegel die Ehe einging. Zu diesem Kreis, der sich in Jena in der zweiten Halfte der 1790er Jahre zusammenfand, gehorten weiterhin: Friedrich von Hardenberg, der sich das Pseudonym Novalis gab, (1772–1801), Ludwig Tieck (1773–1853), Wilhelm Heinrich Wackenroder (1773–1798) und August Ludwig Hulsen (1765–1810). Zum naheren Umfeld als standige Gesprachspartner und Vertraute in dieser fruhromantischen Zeit ist auch Friedrich Daniel Ernst Schleiermacher (1768–1834) zu zahlen.