Naoko Saito

Functional Analysis of Rpn6p, a Lid Component of the 26 S Proteasome, Using Temperature-sensitive rpn6 Mutants of the Yeast Saccharomyces cerevisiae

Rpn6p is a component of the lid of the 26 S proteasome. We isolated and analyzed two temperature-sensitive rpn6 mutants in the yeast, Saccharomyces cerevisiae. Both mutants showed defects in protein degradation in vivo. However, the affinity-purified 26 S proteasome of the rpn6 mutants grown at the permissive temperature degraded polyubiquitinated Sic1p efficiently, even at a higher temperature. Interestingly, their enzyme activity was even higher at a higher temperature, indicating that once made mutant proteasomes are stable and have little defect in the proteolytic function. These results suggest that the deficiency in protein degradation observed in vivo is rather due to a defect in the assembly of a holoenzyme at the restrictive temperature. Indeed, both rpn6 mutants grown at the restrictive temperature were defective in assembling the 26 S proteasome. A striking feature of the rpn6 mutants at the restrictive temperature was that there appeared a protein complex composed of only four of the nine lid components, Rpn5p, Rpn8p, Rpn9p, and Rpn11p. Altogether, we conclude that Rpn6p is essential for the integrity/assembly of the lid in the sense that it is necessary for the incorporation of Rpn3p, Rpn7p, Rpn12p, and Sem1p (Rpn15p) into the lid, thereby playing an essential role in the proper function of the 26 S proteasome.

In search of the public and the private: philosophy of education in post-war Japan

The focus of this paper is on Japanese philosophy of education in the post-war period. We begin with a historical account, concentrating on developments in ideas and their interrelation with policy, and then go on to discuss aspects of the contemporary scene. Central to our concerns here are the ways in which there has been an impoverishment of the public and private realms, especially with the collusion of private and national interests under the sway of neo-liberal and neo-conservative ideologies. We conclude our discussion by identifying some current trends in Japanese philosophy of education, highlighting ways in which new developments in the subject may lay the way for restoring and enhancing the relationship between the private and the public.

Pragmatism and the tragic sense: Deweyan growth in an age of nihilism

In the context of contemporary nihilistic tendencies in democracy and education, Dewey’s pragmatism must respond to the criticism that it lacks a tragic sense. By highlighting the Emersonian perfectionist dimension latent in the concept of growth, this paper attempts to reveal a sense of the tragic in Dewey’s work—his humble recognition of the double nature of democracy as both attained and unattained. It is precisely the lack of this sense of the tragic that characterises contemporary nihilism. In resistance to this, Deweyan growth points to a perfectionist education committed to the re–awakening of intensity of impulse.

Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systematic amyloidosis characterized by lattice corneal dystrophy, cranial neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish population, FAF is a considerably rare disorder in other regions. In this study, we examined the clinical characteristics as well as the haplotypes of six Japanese patients with FAF from five families. They showed the typical clinical presentations of FAF, but we found a broad range of ages at onset of neurological symptoms. All members had the c.654G>A mutation in GSN. To evaluate the disease haplotypes, high-density single-nucleotide polymorphism (SNP) arrays were used and disease-relevant haplotypes were reconstructed. Haplotype analysis in the four apparently unrelated families suggested a common founder haplotype. In a sporadic FAF patient, however, the haplotype was dissimilar to the founder haplotype. The present study demonstrated that a founder mutation in most of the Japanese families with FAF, except for a sporadic patient in whom a de novo mutation event was suggested as the origin of the mutation.

Reconstruction in Dewey's Pragmatism: Home, Neighborhood, and Otherness

John Dewey was engaged, throughout his work, in the reconstruction of American democracy and education. Committed to that philosophy for and in action that is pragmatism, a philosophy for solving the problems of human beings, he addressed himself to what he saw as the crisis of democracy in twentieth-century America. In 1927, discussing the erosion of the public sphere in American society, Dewey criticized what he saw as the hollow concept and practice of “citizenship” in democracy. In the “void between government and the public,” men became, he warned, “skeptical of the efficiency of political action.” 1 Indifference and apathy are the signs of a bewildered public—a state where one does not know “what one really wants.” 2 This is a kind of existential crisis of democracy. Dewey reminds us that the phenomenon of the “eclipse of the public” 3 has a bearing not only on democracy as a matter of deliberative procedure or political participation, but also on one’s way of living, on an ethical dimension of life: the question of how one should live a good life. For him, the political task of democracy, what it means to be a citizen, is inseparable not only from the ethical but also from the educational—a dimension of education that involves the internal transformation of human being. He proposed the recreation of the “Great Community”—a public space in which different individual voices are heard through mutual learning and cooperation. How I should live is inseparably related to how I live with others. In the beginning of the twenty-first century the significance of Dewey’s prag matism needs to be critically reconsidered not only in America, but also on a global scale. Americanization, as both a dimension and an engine of globalization, flat tens, rather than enhances, global awareness; or worse, it assimilates, in the name of hospitality, the different, the foreign, and the silent into its own home. Privatiza

Construction of Trinervitane and Kempane Skeletons Based on Biogenetical Routes

Based on the putative biogenesis of trinervitane- and kempane-type diterpenes (Scheme 1), a biogenetic-type transformation was simulated by cyclization of 7,16-secotrinervita-7,11,15-triene-2α,3α,17-triol (23) and of its 17-chloro derivative 30. The requisite substrates were prepared from geranylgeranoic acid chloride 6 (Schemes 2, 4, and 5). Treatment of 30 with AgClO4 at −20° provided the trinervitantrienediols 32 and 33 in 68 and 5% yields, while kempadienediol 35 was obtained in 50% yield by the same reagent at +20° (Scheme 7). The structures of the cyclization products were elaborated from detailed inspection of NMR spectra including H,H COSY, C,H COSY, and NOESY (Tables 1 and 2). The conformation of 30 and its plausible cyclization intermediate was discussed with the help of physical evidence, including X-ray crystallographic analysis.

Beyond monolingualism: philosophy as translation and the understanding of other cultures

Beyond a monolingual mentality and beyond the language that is typically observed in the prevalent discourse of education for understanding other cultures, this article tries to present another approach: Stanley Cavells idea of philosophy as translation. This Cavellian approach shows that understanding foreign cultures involves a relation to other cultures already within ones native culture. Foreshadowing the Cavellian sense of tragedy, Emersons ‘Devils child’ helps us detect the sources of repression and blindness that are hidden behind the foundationalist approach to other cultures. The child represents the human condition in which the self and language are simultaneously in the process of translation. On the strength of this I propose a possibility of understanding other cultures that is crucially related to language education, one that can point us beyond monolingualism. Cavells view of language and the self envisions a way of releasing, not repressing, the desire to express ones inner light as a crucial source of the revival of ones native culture from within, while at the same time cultivating an eye for the other, the stranger, who is already here within oneself. This is to find alterity in the human condition in terms of the translation that is inherent to language and the immigrancy of the self.

Awakening My Voice: Learning from Cavell's perfectionist education

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American philosophy and its Eastern strains: Crisis, resilience, and self-transcendence

Abstract This paper will critically reconsider the potential of Dewey’s pragmatist idea of security without foundation. There is some potential in his anti-foundationalism as a form of wisdom for living beyond the risk society. I shall argue that Deweyan critical thinking needs to be further reconstructed, and even to be destabilized, if it is to exercise its best possible power of transcendence. One way to do this is to open its boundaries towards the ‘East’, towards European poststructuralism as well as towards East Asia, thereby destabilizing and transcending the limit of pragmatism. And I propose to do this through the mediation of Stanley Cavell’s rereading of Emerson’s and Thoreau’s American transcendentalism.

Taking a Chance: Education for Aesthetic Judgment and the Criticism of Culture.

This article explores the possibilities of the antifoundationalist thought of Cavell with a particular focus on his idea of chance in aesthetic experience, as a framework through which to destabilize the prevailing discourse of education centering on freedom and control. I try to present the idea of chance in a particular way, which does not identify it with chaos or limitlessness but takes it rather as a condition of meaning-making, and more generally of a perfecting of culture, of a conscientious sense of its further possibility and betterment. In Cavells perfectionism, our aesthetic life models our political life, and such life requires our constant reengagement with our language. The cultural criticism this entails is to be understood not in merely negative terms but as itself a process of renewal. The interrelationship between the aesthetic, the political and language is at the heart of Cavellian education for self-knowledge, where this is understood as a matter of self-criticism. It connects, therefore, with Cavells sustained commitment to challenging philosophys self-knowledge. Along these lines, reference is made to John Cages idea of chance in art. Cage is an American composer who was influenced by Thoreau and whose idea of chance has, perhaps because of this, some similarity to Cavells. Discussing these antifoundationalist American writers, I argue that criticism of culture requires trust in ones taste, which is at the heart of aesthetic judgment. ‘Taking a chance’ is a mode of thinking and use of language that might replace a prevalent discourse of critical thinking in education and realize a possibility of liberal education beyond the dichotomy of freedom and control.