904 research outputs found

    Bioluminescence Resonance Energy Transfer Reveals the Adrenocorticotropin (ACTH)-Induced Conformational Change of the Activated ACTH Receptor Complex in Living Cells

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    Bioluminescence resonance energy transfer analysis is used to study the interaction between melanocortin 2 receptor (MC2R) accessory protein and the MC2R and provides evidence for protein kinase A-dependent conformational changes in the receptor complex following receptor activation. The melanocortin 2 receptor (MC2R) accessory protein (MRAP) is a small single-transmembrane domain protein that plays a pivotal role in the function of the MC2R. The pituitary hormone, ACTH, acts via this receptor complex to stimulate adrenal steroidogenesis. Using both coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that the MC2R is constitutively homodimerized in cells. Furthermore, consistent with previous data, we also show that MRAP exists as an antiparallel homodimer. ACTH enhanced the BRET signal between MC2R homodimers as well as MC2R-MRAP heterodimers. However, ACTH did not enhance the physical interaction between these dimers as determined by coimmunoprecipitation. Real-time BRET analysis of the MRAP-MC2R interaction revealed two distinct phases of the ACTH-dependent BRET increase, an initial complex series of changes occurring over the first 2 min and a later persistent increase in BRET signal. The slower ACTH-dependent phase was inhibited by the protein kinase A inhibitor KT5720, suggesting that signal transduction was a prerequisite for this later conformational change. The MRAP-MC2R BRET approach provides a unique tool with which to analyze the activation of this receptor

    The Oxford handbook of Japanese philosophy /

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    "Japanese philosophy is now a flourishing field with thriving societies, journals, and conferences dedicated to it around the world, made possible by an ever-increasing library of translations, books, and articles. The Oxford Handbook of Japanese Philosophy is a foundation-laying reference work that covers, in detail and depth, the entire span of this philosophical tradition, from ancient times to the present. It introduces and examines the most important topics, figures, schools, and texts from the history of philosophical thinking in premodern and modern Japan. Each chapter, written by a leading scholar in the field, clearly elucidates and critically engages with its topic in a manner that demonstrates its contemporary philosophical relevance. 0The Handbook opens with an extensive introductory chapter that addresses the multifaceted question, "What is Japanese Philosophy?" The first fourteen chapters cover the premodern history of Japanese philosophy, with sections dedicated to Shinto and the Synthetic Nature of Japanese Philosophical Thought, Philosophies of Japanese Buddhism, and Philosophies of Japanese Confucianism and Bushido. Next, seventeen chapters are devoted to Modern Japanese Philosophies. After a chapter on the initial encounter with and appropriation of Western philosophy in the late nineteenth-century, this large section is divided into one subsection on the most well-known group of twentieth-century Japanese philosophers, The Kyoto School, and a second subsection on the no less significant array of Other Modern Japanese Philosophies. Rounding out the volume is a section on Pervasive Topics in Japanese Philosophical Thought, which covers areas such as philosophy of language, philosophy of nature, ethics, and aesthetics, spanning a range of schools and time periods."--Includes bibliographical references and index.Miki Kiyoshi: Marxism, humanism, and the power of imagination / Melissa Anne-Marie Curley -- Nishitani Keiji: practicing philosophy as a matter of life and death / Graham Parkes -- Ueda Shizuteru: the self that is no a self in a twofold world / Steffen Doll -- Watsuji Tetsuro: the mutuality of climate and culture and an ethics of betweeness / Erin McCarthy -- Kuki Shuzo: a phenomenology of fate and chance and an aesthetics of the floating world / Graham Mayeda -- Comparative philosophy in Japan: Nakamura Jajime and Izutsu Toshihiko / John W.M. Krummel -- Japanese Christian philosophies / Terao Kazuyoshi -- Yuasa Yasuo's philosophy of self-cultivation: a theory of embodiment / Shigenori Nagatomo -- Postwar Japanese political philosophy: Marxism, liberalism, and the quest for autonomy / Rikki Kersten -- Raicho: Zen and the female body in the development of Japanese feminist philosophy / Michiko Yusa and Leah Kalmanson -- Japanese phenomenology / Tani Toru --^Modern Zen thinkers: D.T. Suzuki, Hisamatsu Shin'ichi, and Masao Abe / Mori Tetsuro (trans. Bret W. Davis), Minobe Hitoshi (trans. Bret W. Davis), and Steven Heine -- Japanese neo-Confucian philosophy / John A. Tucker -- Ancient learning: the Japanese revival of classical Confucianism / John A. Tucker -- Bushido and philosophy: parting the clouds, seeking the way / Chris Goto-Jones -- The Japanese encounter with and appropriation of Western philosophy / John C. Maraldo -- The Kyoto School: transformations over three generations / Ohashi Ryosuke and Akitomi Katsuya (trans. Bret W. Davis) -- The development of Nishida Kitaro's philosophy: pure experience, place, action-intuition / Fujita Masakatsu (trans. Bret W. Davis) -- Nishida Kitaro's philosophy: self, world, and the nothingness underlying distinctions / John C. Maraldo -- The place of God in the philosophy of Tanabe Hajime / James W. Heisig --^The Komaba Quartet: a landscape of Japanese philosophy in the 1970s / Kobayashi Yasuo -- Philosophical implications of the Japanese language / Rolf Elberfeld (trans. Bret W. Davis) -- Natural freedom: human/nature nondualism in Zen and Japanese thought / Bret W. Davis -- Japanese ethics / Robert E. Carter -- Japanese (and Ainu) aesthetics and philosophy of art / Mara Miller and Yamasaki Koji -- The controversial cultural identity of Japanese philosophy / Yoko Arisaka.Introduction: what is Japanese philosophy? / Bret W. Davis -- Prince Shotoku's Constitution and the synthetic nature of Japanese thought / Thomas P. Kasulis -- Philosophical implications of Shinto / Iwasawa Tomoko -- National learning: poetic emotionalism and nostalgic nationalism / Peter Flueckiger -- Saicho's Tendai: in the middle of form and emptiness / Paul L. Swanson and Brook Ziporyn -- Kukai's Shingon: embodiment of emptiness / John W.M. Krummel -- Philosophical dimensions of Shinran's Pure Land Buddhist path / Dennis Hirota -- Modern Pure Land thinkers: Kiyozawa Manshi and Soga Ryojin / Mark Unno -- The philosophy of Zen master Dogen: egoless perspectivism / Bret W. Davis -- Dogen on the language of creative textual hermeneutics / Steven Heine -- Rinzai Zen Koan training: philosophical intersections / Victor Sogen Hori --^"Japanese philosophy is now a flourishing field with thriving societies, journals, and conferences dedicated to it around the world, made possible by an ever-increasing library of translations, books, and articles. The Oxford Handbook of Japanese Philosophy is a foundation-laying reference work that covers, in detail and depth, the entire span of this philosophical tradition, from ancient times to the present. It introduces and examines the most important topics, figures, schools, and texts from the history of philosophical thinking in premodern and modern Japan. Each chapter, written by a leading scholar in the field, clearly elucidates and critically engages with its topic in a manner that demonstrates its contemporary philosophical relevance. 0The Handbook opens with an extensive introductory chapter that addresses the multifaceted question, "What is Japanese Philosophy?" The first fourteen chapters cover the premodern history of Japanese philosophy, with sections dedicated to Shinto and the Synthetic Nature of Japanese Philosophical Thought, Philosophies of Japanese Buddhism, and Philosophies of Japanese Confucianism and Bushido. Next, seventeen chapters are devoted to Modern Japanese Philosophies. After a chapter on the initial encounter with and appropriation of Western philosophy in the late nineteenth-century, this large section is divided into one subsection on the most well-known group of twentieth-century Japanese philosophers, The Kyoto School, and a second subsection on the no less significant array of Other Modern Japanese Philosophies. Rounding out the volume is a section on Pervasive Topics in Japanese Philosophical Thought, which covers areas such as philosophy of language, philosophy of nature, ethics, and aesthetics, spanning a range of schools and time periods."-

    The life of Bret Harte

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    As part of the Open Door series, Gary Scharnhorst, author of ""Bret Harte : opening the American literary West,"" discusses the life of Bret Harte

    Richard Davis at desk

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    Richard Davis, executive director with Business and Industry Institute of JCCC (renamed the Center for Business and Technology in 2000) at desk in 198

    Clifford Davis for This Month

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    Clifford Davis (Student practical nurse) of Johnson County A.V.T.S. (Area Vocational Technical Schools) poses for magazine "This Month"(now Imprint) on March 8th, 200

    Harte, Bret

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    Bret Harte was an American author and poet whose short stories provided a glimpse of frontier life. Harte began his career as a Journalist in Union, CA; he later moved to San Francisco and published a collections of poetry and parodies. In 1870 his first collection of Western stories was published, soon afterwards he accepted a writing contract with Atlantic Monthly and moved to the East. In his later life his writing lost popularity forcing him to accept consulships in Germany and Scotland. He moved to London permanently in 1885, where he died in 1902.4 x 6.5 in; Cabinet car

    Harte, Bret

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    Bret Harte was an American author and poet whose short stories provided a glimpse of frontier life. Harte began his career as a Journalist in Union, CA; he later moved to San Francisco and published a collections of poetry and parodies. In 1870 his first collection of Western stories was published, soon afterwards he accepted a writing contract with Atlantic Monthly and moved to the East. In his later life his writing lost popularity forcing him to accept consulships in Germany and Scotland. He moved to London permanently in 1885, where he died in 1902.Carte de visit

    Type-3 BRET, an Improved Competition-Based Bioluminescence Resonance Energy Transfer Assay

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    AbstractWe show that in conventional, competition-based bioluminescence resonance energy transfer (BRET) assays of membrane protein stoichiometry, the presence of competitors can alter tagged-protein density and artifactually reduce energy transfer efficiency. A well-characterized monomeric type I membrane protein, CD86, and two G protein-coupled receptors β2AR and mCannR2, all of which behave as dimers in these conventional assays, exhibit monomeric behavior in an improved competition-based type-3 BRET assay designed to circumvent such artifacts

    Constraints on GPCR heterodimerization revealed by the type-4 induced-association BRET assay

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    G-protein-coupled receptors (GPCRs) comprise the largest and most pharmacologically important family of cell-surface receptors encoded by the human genome. In many instances, the distinct signaling behavior of certain GPCRs has been explained in terms of the formation of heteromers with, for example, distinct signaling properties and allosteric cross-regulation. Confirmation of this has, however, been limited by the paucity of reliable methods for probing heteromeric GPCR interactions in situ. The most widely used assays for GPCR stoichiometry, based on resonance energy transfer, are unsuited to reporting heteromeric interactions. Here, we describe a targeted bioluminescence resonance energy transfer (BRET) assay, called type-4 BRET, which detects both homo- and heteromeric interactions using induced multimerization of protomers within such complexes, at constant expression. Using type-4 BRET assays, we investigate heterodimerization among known GPCR homodimers: the CXC chemokine receptor 4 and sphingosine-1-phosphate receptors. We observe that CXC chemokine receptor 4 and sphingosine-1-phosphate receptors can form heterodimers with GPCRs from their immediate subfamilies but not with more distantly related receptors. We also show that heterodimerization appears to disrupt homodimeric interactions, suggesting the sharing of interfaces. Broadly, these observations indicate that heterodimerization results from the divergence of homodimeric receptors and will therefore likely be restricted to closely related homodimeric GPCRs

    Fondation et transmission dans la Vita Pauli et la Vita Hilarionis

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    International audiencePaul and Anthony, Anthony and Hilarion, Hilarion and Hesychius /…/, thementor-disciple relationships punctuate Jerome’s Vita Pauli and Vita Hilarionis,and forge an almost genetic continuity between a founder and his successors. This article will ask how these inheritance relationships reflect Jerome’s intentions in the ascetic and literary fields. These two Lives of monks make sure to place their hero in a monastic line that goes back to the origins. The Vita Pauli says almost nothing about the ascetic’s life and focuses on his encounter with Anthony, who becomes his heir in all thanks to biblical parallels. Hilarion, for his part, begins his monastic life by meeting a mentor and ends it with an act of transmission to one of his disciples. Each time, the ascetic garment, the most immediately visible sign of the monastic ideal given by a monk to his disciples, becomes a symbolic representation of this spiritual lineage. Consequently, this emphasis on transmission can be read as a doubling of the Vitae’s exemplary aim, the reader becoming the disciple of the mentor the saint is for him. However, this motif also becomes for Jerome a way to define his place in the literary hagiographic tradition: both a rival imitator of the Vita Antonii and the first Latin author of Lives of ascetics aspiring to create emulators.Les rapports entre mentor et disciple scandent la Vita Pauli et la Vita Hilarionis de Jérôme et tissent une continuité presque héréditaire entre un fon-dateur et ses successeurs. Le but de cet article est de se demander comment ces relations de transmission témoignent des ambitions de Jérôme tant dans le domaine ascétique que littéraire. Ces deux Vies de moines, tout d’abord, veillent à préciser la place de leur héros dans une lignée de moines qui remonte aux origines. La Vie de Paul ne dit presque rien de la vie de l’ascète et se concentre sur sa rencontre avec Antoine, qui devient en tout son héritier grâce à des parallèles bibliques. Hilarion, quant à lui, commence sa vie monastique par la rencontre avec un mentor et la termine dans la transmission à l’un de ses disciples. À chaque fois, le vêtement ascétique, signe le plus immédiatement visible de l’idéal monastique, transmis d’un moine à son disciple, se fait représentation symbolique de cette filiation spirituelle. Cette insistance sur la transmission peut alors être lue comme un redoublement de la visée exemplaire des Vitae, où le lecteur devient le disciple du mentor qu’est pour lui le saint. Mais ce motif devient également pour Jérôme le moyen de définir sa place dans la tradition littéraire hagiographique : à la fois rival et imitateur de la Vie d’Antoine, et premier auteur latin de Vies d’ascètes aspirant à créer lui-même des émules
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