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Sample records for huntington hobbs iv

  1. Hobbes on natural philosophy as "True Physics" and mixed mathematics.

    Science.gov (United States)

    Adams, Marcus P

    2016-04-01

    In this paper, I offer an alternative account of the relationship of Hobbesian geometry to natural philosophy by arguing that mixed mathematics provided Hobbes with a model for thinking about it. In mixed mathematics, one may borrow causal principles from one science and use them in another science without there being a deductive relationship between those two sciences. Natural philosophy for Hobbes is mixed because an explanation may combine observations from experience (the 'that') with causal principles from geometry (the 'why'). My argument shows that Hobbesian natural philosophy relies upon suppositions that bodies plausibly behave according to these borrowed causal principles from geometry, acknowledging that bodies in the world may not actually behave this way. First, I consider Hobbes's relation to Aristotelian mixed mathematics and to Isaac Barrow's broadening of mixed mathematics in Mathematical Lectures (1683). I show that for Hobbes maker's knowledge from geometry provides the 'why' in mixed-mathematical explanations. Next, I examine two explanations from De corpore Part IV: (1) the explanation of sense in De corpore 25.1-2; and (2) the explanation of the swelling of parts of the body when they become warm in De corpore 27.3. In both explanations, I show Hobbes borrowing and citing geometrical principles and mixing these principles with appeals to experience. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. HOBBES AND SPINOZA

    DEFF Research Database (Denmark)

    Jarvad, Ib Martin

    2006-01-01

    social pact of submission and argued for the sociableness of man as a natural emotion with a rational basis. Both departed from the self love theory and both claimed their –opposite- results to follow from their axioms and definitions more geometrico; Hobbes that man’s fellow man must be his enemy......the main difference between Hobbes and Spinoza in spite of obvious similarities concerns absolutism. Hobbes believed in absolutism of some sort for man must realise that only some sovereign power could make and enforce laws that make social life possible. Spinoza had no need for the fictitious......, and Spinoza that man’s fellow man is the most useful for him....

  3. Thomas Hobbes: Sobre el miedo

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    Carlos Bührle

    2004-11-01

    Full Text Available This work intend to draw some light upon the role of fear in Hobbes's political thought. It's known that this passion underlies the social contract, in the sense that it drives man to leave the state of nature in order to find security, and also to get rid of the menace of violent death. Taking into account that fear and death are inseparable in Hobbes's philosophy, a fundamental question arises: to what extent can we say that fear vanishes completely after social contract? In Hobbes, fear seems to be an intrinsical feature of men.

  4. Hobbes, Liberalism, and Political Education.

    Science.gov (United States)

    Esquith, Stephen L.

    The connection between liberal political philosophy and political education is discussed with particular emphasis on the philosophy of Thomas Hobbes. The purpose of the essay is to explain how liberal citizens become committed to a distinctively liberal conception of the common good. Part 1 discusses Hobbes' theory that rationally determining…

  5. Logical consistence and operating base in Thomas Hobbes. [Spanish

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    Rusbel Martínez Rodríguez

    2006-01-01

    Full Text Available The aim of this paper is to specify the operative elements included in the Thomas Hobbes philosophy substratum. I defend the idea that the logic in the Hobbes philosophy system depends on this substratum. In this paper I use the idea of «operative and thematic concepts» development by Eugen Fink. These concepts are used to show how all of the Hobbes philosophy system has explicit and implicit concepts. Another aim is to concede the importance of understanding the Hobbes philosophy as holistic.

  6. Religious Conscience and Civic Conscience in Thomas Hobbes's Civic Philosophy.

    Science.gov (United States)

    Pepperell, Keith C.

    1989-01-01

    This article discusses Thomas Hobbes' concept of conscience, the historical context in which the concept was formulated, and Hobbes' conclusion that civil law takes precedence over religious conscience. Hobbes' views are related to the debate between Pratte and Losito over the interaction between religious and civic conscience. (IAH)

  7. Teaching the "Leviathan": Thomas Hobbes on Education

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    Bejan, Teresa M.

    2010-01-01

    This paper considers Thomas Hobbes's educational thought both in its historical context and in the context of his political philosophy as a whole. It begins with Hobbes's diagnosis of the English Civil War as the product of the miseducation of the commonwealth and shows that education was a central and consistent concern of his political theory…

  8. Por que ler Hobbes como um teórico de segurança internacional? Why read Hobbes as a theorist of international security?

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    R. B. J Walker

    2010-06-01

    Full Text Available Thomas Hobbes tornou-se uma figura canônica para teorias de segurança internacional, ainda que seus escritos digam relativamente pouco acerca do que chamaríamos hoje de um sistema internacional. Este artigo sugere que Hobbes permanece importante para a análise de segurança internacional, assim como para a teoria política de modo mais geral, não por desenvolver qualquer teoria coerente de Relações Internacionais, mas sim porque sua consideração sobre a soberania de Estados particulares exige uma análise sobre as condições de possibilidade externas de tais Estados. Uma política após Hobbes precisa tratar dos efeitos constitutivos de sua filosofia da história particular. Assim, este artigo propõe uma leitura política de Hobbes, a qual enfatiza sua importância para o pensamento da política moderna e de suas condições de possibilidade; de suas origens e limites, que são também nossas origens e limites enquanto sujeitos modernos.Thomas Hobbes has become a canonical figure for theories of international security even though his writings say relatively little about what we would now call an international system. This paper suggests that Hobbes remains important for the analysis of international security, as well as for political theory more generally, not because he advances any coherent theory of international relations but because his account of the sovereignty of particular states requires an account of the external conditions of possibility of such states. Politics after Hobbes needs to get to grips with the constitutive effects of his particular philosophy of history. Thus, this paper proposes a political reading of Hobbes that emphasizes his importance for thought about modern politics and its conditions of possibility; about its origins and limits that are also our origins and limits as modern subjects.

  9. The Sovereign as Educator: Thomas Hobbes's National Curriculum.

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    Parry, Geraint

    1998-01-01

    Focuses on Thomas Hobbes, an English political philosopher who argued that the solution to civil disorders lay in a sovereign authority backed with force. Argues that education should be seen at the center of Hobbes's project of rescuing society from the disorders threatening civilization throughout 17th-century Europe. (CMK)

  10. Thomas Hobbes' Leviathan

    NARCIS (Netherlands)

    Konijnenburg, Willem van

    1945-01-01

    De analyse van den Laviathan. Het probleem dat Hobbes probeerde op te lossen luidt: ,,waartoe" en ,,hoe" is er gezag. Het ,,waartoe" bleek schuil te gaan in de praemisse der bevordering en handhaving der vrede. Het ,,hoe" van het gezag gaf aanleiding tot de aanname van het sluiten van een

  11. O Estado cristão em Thomas Hobbes

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    Daniel Artur Emidio Branco

    2016-12-01

    Full Text Available O presente artigo tem como finalidade a investigação do pensamento do filósofo inglês Thomas Hobbes (1588-1679, mais precisamente a relação entre Igreja e Estado, valendo-se de suas obras, em especial Leviatã (1651. Com o título O Estado Eclesiástico em Thomas Hobbes, o artigo busca mostrar como as conclusões de Hobbes acerca do papel da Igreja no Estado são relevantes para o século XXI. A concepção de Evangelho de Cristo como um reino de outro mundo, a natureza privada da fé, o pontificado do soberano como aquele que se posiciona está entre Deus e os homens, a união entre Lei Mosaica e Lei Natural e a união entre Igreja e Estado são os delimitadores do grande tema, que busca levar o leitor contemporâneo ao conhecimento das conclusões de Hobbes e, assim, considerar a aplicação das mesmas a sua geração.

  12. Bioethics and deliberative democracy: five warnings from Hobbes.

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    Trotter, Griffin

    2006-06-01

    Thomas Hobbes is one of the most ardent and thoroughgoing opponents of participatory democracy among Western political philosophers. Though Hobbes's alternative to participatory democracy-assent by subjects to rule by an absolute sovereign-no longer constitutes a viable political alternative for Westerners, his critique of participatory democracy is a potentially valuable source of insight about its liabilities. This essay elaborates five theses from Hobbes that stand as cogent warnings to those who embrace participatory democracy, especially those (such as most bioethicists) advocating for deliberative democracy based on a rational consensus model. In light of these warnings, the author suggests an alternative, modus vivendi approach to deliberative democracy that would radically alter the current practice of bioethics.

  13. Modern Restlessness, from Hobbes to Augustine

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    Peter Busch

    2015-05-01

    Full Text Available Only with difficulty do modern readers grasp the full import of Augustine’s confession, “Restless is our heart, until it rests in you”, or seriously consider that it might be true. An unexpected remedy is to be found in reading Thomas Hobbes, who introduces and defends the view of happiness that is now commonly accepted without argument. According to Hobbes, human beings find their happiness not in a single, supreme good but in many objects, the securing of which requires a lifelong quest for power. But this teaching, influential and revealing though it is, fails to satisfy. Meditating on that dissatisfaction is a first step towards more serious engagement with Augustine.

  14. THE INTERNATIONAL RELATIONS IN THE THOUGHT OF THOMAS HOBBES AS RELAÇÕES INTERNACIONAIS NO PENSAMENTO DE THOMAS HOBBES

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    Gabriel Ribeiro Barnabé

    2010-10-01

    Full Text Available We shall examine how Hobbes conceives the international relations as a scenario of permanent hostility, his contribution to the realist theory of international relations and the strategies for the attainment of peace or the maximization of benefits. We shall investigate the hobbesian equation between state of nature, international relations and state of war, the characteristics of the state of nature, the properties of foreign war and its causes, and the mechanism of balance of power. We shall also analyze the natural law, which is the law of nations, and the calculation to adhere to these laws. Finally, we shall do a general analysis of Hobbes's contribution to the theory of international relations.Examinaremos como Hobbes concebe as relações internacionais enquanto um cenário de permanente hostilidade, sua contribuição para a teoria realista das relações internacionais e as estratégias para a consecução da paz ou a maximização dos benefícios. Investigaremos a equação hobbesiana entre estado de natureza, relações internacionais e estado de guerra, as características do estado de guerra, as propriedades da guerra externa e suas causas e o mecanismo de balanço de poder. Analisaremos, também, a lei natural, que é a lei das nações, e o cálculo para aderir a essas leis. Por fim, faremos uma análise genérica da contribuição de Hobbes para a teoria das relações internacionais.

  15. Sobre o desejo em Thomas Hobbes

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    Fernando Rodrigues Montes D'Oca

    2011-01-01

    Full Text Available O objetivo deste artigo é explicar o papel do desejo na filosofia política do filósofo inglês Thomas Hobbes. Para tanto, o presente estudo propõe-se apresentar: i. a razão por que Hobbes reivindica o desejo à política, i.a tratando da teoria da conservação do movimento, de Galileu Galilei, e i.b da felicidade como um sucesso contínuo na obtenção dos objetos de desejo; e ii. o papel do desejo no estado de natureza, já que este é determinante tanto para ii.a a entrada do homem no estado de guerra quanto ii.b para a saída deste estado.

  16. El contrato social en Hobbes: ¿absolutista o liberal?

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    Francisco Cortés Rodas

    Full Text Available En este artículo se presentan los elementos centrales del modelo contractualista clásico de legitimación del Estado, expuesto por Thomas Hobbes en el Leviatán. Se cuestiona la interpretación propuesta por Leo Strauss sobre la filosofía política de Hobbes, según la cual, el filósofo inglés sería el fundador del liberalismo. Mediante una interpretación de la teoría de la representación política hobbesiana se intenta destacar su imagen como defensor del absolutismo político. El tipo de liberalismo a partir del cual es posible mostrar que la concepción de Hobbes resulta inaceptable es el liberalismo representado por autores como Benjamin Constant, Madame de Stäel y Alexis de Tocqueville.

  17. El contrato social en Hobbes: ¿absolutista o liberal?

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    Francisco Cortés Rodas

    2010-01-01

    Full Text Available En este artículo se presentan los elementos centrales del modelo contractualista clásico de legitimación del Estado, expuesto por Thomas Hobbes en el Leviatán. Se cuestiona la interpretación propuesta por Leo Strauss sobre la filosofía política de Hobbes, según la cual, el filósofo inglés sería el fundador del liberalismo. Mediante una interpretación de la teoría de la representación política hobbesiana se intenta destacar su imagen como defensor del absolutismo político. El tipo de liberalismo a partir del cual es posible mostrar que la concepción de Hobbes resulta inaceptable es el liberalismo representado por autores como Benjamin Constant, Madame de Stäel y Alexis de Tocqueville.

  18. Nom comú i nom propi segons Thomas Hobbes

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    Josep Moran i Ocerinjauregui

    2014-01-01

    Full Text Available Thomas Hobbes (1588-1679 tracta el llenguatge humà, i més concretament els noms, des d’un punt de vista filosòfic. Per a Hobbes, els noms són designadors de conceptes: els noms propis designen una sola cosa mentre que els noms comuns en designen diverses. Aquestes idees van ser objecte de reflexió filosòfica i van tenir gran influència en altres filòsofs, com John Stuart Mill.

  19. Shakespeare and Hobbes

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    Nicholas Dungey

    2012-05-01

    Full Text Available Thomas Hobbes sought a reconstruction of philosophy, ethics, and politics that would end, once and for all, the bitter disputes that led to the English Civil War. This reconstruction begins with the first principles of matter and motion and extends to a unique account of moral consent and political obligation. However, the author contends that his materialist account of human nature gives rise to a set of perceptions, imaginings, and desires that contribute to the chaos of the state of nature. He argues that the sort of person that emerges from Hobbes’s materialist anthropology is unlikely to be able, or unwilling, to make the necessary agreements about common meaning and language that constitute the ground of the social contract. Following Hobbes’s materialist anthropology, Shakespeare’s Macbeth, and not the rational actor who consents to the social contract, is the more likely result. Performed approximately 25 years before Leviathan appeared, Macbeth provides a literary version of the state of nature, and expresses many of the themes that Hobbes later gave philosophical explanation to. The author suggests that we interpret Macbeth through Hobbes’s materialism. On this reading, the crisis of Macbeth is caused by the material motion of Macbeth’s senses, imagination, and desires. Macbeth provides graphic examples of the type of problems that the author suggests arise from Hobbes’s materialism, and it illuminates the political significance of Macbeth.

  20. Science and Rhetoric From Bacon to Hobbes; Responses to the Problem of Eloquence.

    Science.gov (United States)

    Zappen, James P.

    Decisive changes in the history of rhetoric occurred with the publication of Francis Bacon's "Advancement of Learning" and "De augmentis scientiarum" and "Leviathan" by Thomas Hobbes. Bacon and Hobbes responded to the problem of eloquence common to scientists in the early seventeenth century, which centered on three…

  1. Hobbes, los juristas y el nuevo constitucionalismo

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    Raquel García Bouzas

    2014-01-01

    Full Text Available El actual debate sobre la relación entre el derecho y la moral demuestra la complejidad del problema de encontrar las propiedades formales del derecho en la dimensión de los procedimientos jurídicos institucionalizados, intentando saber si estos procedimientos regulan discursos jurídicos que sean permeables a argumentaciones morales. Habermas ha propuesto la legitimación del derecho mediante la legalidad proveniente de los procedimientos de producción de las normas jurídicas, en tanto que sean racionales también en el sentido de la racionalidad procedimental moral-práctica. El debate continúa en otros autores.En la historia de las ideas jurídicas la importancia de este debate se revela en otros autores que, como Hobbes, también intentaron sustentar en valores morales un orden jurídico positivo, oscilando en ese esfuerzo entre las fronteras del positivismo jurídico y las del iusnaturalismo. Los argumentos morales de la teoría de Hobbes sobre el estado pasan a veces desapercibidos en el conjunto de la enorme producción de sus comentaristas actuales y pasados, quedando limitados al principio de obligatoriedad moral del cumplimiento de los contratos. Pero una lectura de la obra de Hobbes que tenga en cuenta la relación entre la moral y del derecho puede mostrar mucho más.

  2. Argumentos para uma dissociação da filosofia política de Thomas Hobbes da tradição realista Arguments for a dissociation of Thomas Hobbes' political philosophy from the realist tradition

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    Iara Costa Leite

    2005-06-01

    Full Text Available O propósito deste artigo é desconsagrar o caráter heróico que a obra de Hobbes assumiu para os estudantes de relações internacionais ao ter sido enquadrada - assim como as de Tucídides, Maquiavel, Rousseau, Hegel etc. - no épico realista. Veremos que a subsunção do filósofo à "tradição realista" é raramente questionada, mesmo pelos críticos das concepções veiculadas por essa tradição. Assim, o nome de Hobbes permanece, em grande medida, associado à analogia entre anarquia internacional e estado de natureza. Em primeiro lugar, o artigo resgata o caráter hipotético do modelo de estado de natureza, dando ênfase especial ao reconhecimento de Hobbes à limitação de seu reducionismo motivacional para a descrição da realidade. Em segundo, partindo do pressuposto de que a dicotomia interno-externo era inexistente na época de Hobbes, explora, a partir de sua obra, o argumento de que a paz internacional estaria diretamente relacionada à resolução do problema da ordem nas sociedades domésticas.The purpose of this article is to deconsecrate the heroic status that international relations students have attached to Hobbes's texts - an attachment that results from their inclusion, together with texts by Thucydides, Machiavelli, Rousseau and Hegel, in the realist epic. We will see that the subsuming of the philosopher under the "realist tradition" is rarely questioned, even by the critics of the conceptions endorsed by it. Therefore, the name of Hobbes remains, in a large extent, associated to the analogy between international anarchy and the state of nature. In the first place, we'll bring to light the hypothetical status of the state of nature model, emphasizing the fact that Hobbes himself recognized the limitation of its motivational reductionism to the description of reality. Secondly, having taken as a premise the fact that the dichotomy inside/outside did not exist in Hobbes's time, we'll explore the argument that

  3. Two Liberal Trajectories of Civic Education: The Political and Educational Thought of Hobbes and Winstanley.

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    Snauwaert, Dale T.; Theobald, Paul

    1994-01-01

    Compares the political and educational alternatives offered by Thomas Hobbes and Gerrard Winstanley. Sees Hobbes's educational approach, based on negative liberty and state sovereignty, in tension between demands of liberty and conformity. Considers Winstanley's educational approach devoted to independent civic judgment, premised upon positive…

  4. Leviathan and the air-pump Hobbes, Boyle, and the experimental life

    CERN Document Server

    Shapin, Steven

    2011-01-01

    Leviathan and the Air-Pump examines the conflicts over the value and propriety of experimental methods between two major seventeenth-century thinkers: Thomas Hobbes, author of the political treatise Leviathan and vehement critic of systematic experimentation in natural philosophy, and Robert Boyle, mechanical philosopher and owner of the newly invented air-pump. The issues at stake in their disputes ranged from the physical integrity of the air-pump to the intellectual integrity of the knowledge it might yield. Both Boyle and Hobbes were looking for ways of establishing knowledge tha

  5. Soberania e representação: Hobbes, parlamentaristas e levellers Sovereignty and representation: Hobbes, parliamentarians and levellers

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    Eunice Ostrensky

    2010-01-01

    Full Text Available O artigo pretende mostrar que Thomas Hobbes (1588-1679 empregou o conceito de autorização política com o propósito de neutralizar discursos de dois grupos políticos adversários, os quais consideravam a representação um meio eficaz de responsabilizar atores políticos perante seus representados. Entre esses adversários, ocupam lugar de destaque os levellers, por terem proposto, em finais da década de 1640, uma saída constitucional inédita para o problema da ilegitimidade do Parlamento inglês: ampliação do sufrágio seguida da celebração do Acordo do Povo.The article intends to show that Thomas Hobbes (1588-1679 adopted the concept of political authorization as means to fight against the doctrine of the accountability of political actors ahead of the persons they represented. Among these opponents, the levellers have a prominent place, by proposing, in the late 1640s, an innovative solution for the constitutional problem of the illegitimacy of the English Parliament: extension of the franchise followed by a celebration of an Agreement of the People.

  6. L’icona del terrore e dell’ambiguità : Il legame mancante tra Hobbes ed il suo Leviatano

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    Tralau, Johan

    2013-01-01

    Hobbes named his work Leviathan for a Biblical monster, yet he mentioned it only three times in the book itself. Curiously, in those three passages Hobbes speaks of Leviathan in wildly divergent ways: as a machine, man, sovereign, state, and god. In this article, the author argues that we can make sense of this radical ambiguity from a perspective found in the late Antique work Peri hermeneias. Specifically, ambiguity is taken to be conducive to fear, and Hobbes thus employs it as an instrume...

  7. The fool and the franchiser: formal justice in the political theories of Hobbes and Rawls

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    Jan Niklas Rolf

    2016-03-01

    Full Text Available Thomas Hobbes and John Rawls are usually portrayed in antagonistic terms. While Hobbes, one of the first scholars to translate Thucydides, is often held to be an archetypal realist, Rawls, a self-proclaimed follower of Kant, is frequently said to argue from an explicit normative position. In this paper, I try to demonstrate that the two philosophers have more in common than is generally thought. Drawing on Hobbes's answer to the fool and Rawls's analogy of the franchiser, I suggest that there is a powerful link between the two philosophers that can tell us something valuable about their theories of formal justice. Against Brian Barry's characterization of Hobbes as an advocate of justice as mutual advantage and Rawls as a proponent of both justice as mutual advantage and justice as impartiality, I argue that the two philosophers adhere to one and the same tradition of justice, justice as reciprocity, which bases obligations of reciprocity not only on explicit express, but also on tacit acceptance of benefits.

  8. Huntington\\'s disease: Genetic heterogeneity in black African patients

    African Journals Online (AJOL)

    Objective. Huntington's disease (HD) has been reported to occur rarely in black patients. A new genetic variant– Huntington's disease-like 2 (HDL2) – occurring more frequently in blacks, has recently been described. The absence of an expanded trinucleotide repeat at the chromosome 4 HD locus was previously regarded ...

  9. El contrato social en Hobbes: ¿absolutista o liberal? Hobbes’ Social Contract: Absolutist or Liberal?

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    Francisco Cortés Rodas

    2010-12-01

    Full Text Available En este artículo se presentan los elementos centrales del modelo contractualista clásico de legitimación del Estado, expuesto por Thomas Hobbes en el Leviatán. Se cuestiona la interpretación propuesta por Leo Strauss sobre la filosofía política de Hobbes, según la cual, el filósofo inglés sería el fundador del liberalismo. Mediante una interpretación de la teoría de la representación política hobbesiana se intenta destacar su imagen como defensor del absolutismo político. El tipo de liberalismo a partir del cual es posible mostrar que la concepción de Hobbes resulta inaceptable es el liberalismo representado por autores como Benjamin Constant, Madame de Stäel y Alexis de Tocqueville.This article presents the central elements of the classic contractualist model of State legitimacy as displayed by Thomas Hobbes in Leviathan. It aims to question the proposal made by Leo Strauss on Hobbes’ political philosophy according to which Hobbes is the founder of liberalism. Through an interpretation of the Hobbesian theory of political representation, it intends to detach his image as a defender of political absolutism. The type of liberalism from which it is possible to show that Hobbes’ conception is unacceptable, is liberalism represented by authors such as Benjamin Constant, Madame de Stäel and Alexis de Tocqueville.

  10. Jusnaturalismo,Hobbes e dialética

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    José Nicolau Heck - Sidney A. da Silva

    2007-12-01

    Full Text Available Thomas Hobbes é um dos fundadores da moderna concepção de poder político.A instituição do Estado tem no pensador inglês,uma de suas vertentes racionais.O trabalho examina as raízes jusnaturalistas do teórico político ingles e assume a posição de que o legado hobbesiano não é dialetizável. 

  11. Thomas Hobbes: la resistencia política al Leviatán || Thomas Hobbes: Political Resistance To Leviathan

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    Diego Alejandro Fernández Peychaux

    2013-12-01

    Full Text Available RESUMEN En el presente artículo se presentan cuatro claves de lectura de la obra de Thomas Hobbes desde las que fundamentar una noción de resistencia. Este aporte busca, en otras palabras, crear las condiciones de posibilidad de un debate filosófico ofuscado por el mito recurrente sobre el supuesto monstruo de Malmesbury. Una vez hecho esto, se propone delinear las bases de un enfoque metodológico que parta de dicha noción de resistencia. De ese modo, se fundamentaría el primer paso hacia una apropiación ?o expropiación? contemporánea de la matriz hobbesiana de la relación obediencia-seguridad   ABSTRACT This article presents four key of readings about Thomas Hobbes's work, from which it supports a particular notion of resistance. In others words, this contribution searches to create the conditions of posibility for a philosophical debate obfuscated by the recurrent myth about the monster of Malmesbury. Once done that, I offer setting the bases of a metodological aproach which stars from this notion of resistance. Thus, I would back the first step towards a contemporary appropriation ?or expropriation? of the obedience-security relationship within the Hobbesian matrix.  

  12. Thomas Hobbes: la resistencia política al Leviatán || Thomas Hobbes: Political Resistance To Leviathan

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    Diego Alejandro Fernández Peychaux

    2013-12-01

    Full Text Available RESUMEN En el presente artículo se presentan cuatro claves de lectura de la obra de Thomas Hobbes desde las que fundamentar una noción de resistencia. Este aporte busca, en otras palabras, crear las condiciones de posibilidad de un debate filosófico ofuscado por el mito recurrente sobre el supuesto monstruo de Malmesbury. Una vez hecho esto, se propone delinear las bases de un enfoque metodológico que parta de dicha noción de resistencia. De ese modo, se fundamentaría el primer paso hacia una apropiación ?o expropiación? contemporánea de la matriz hobbesiana de la relación obediencia-seguridad   ABSTRACT This article presents four key of readings about Thomas Hobbes's work, from which it supports a particular notion of resistance. In others words, this contribution searches to create the conditions of posibility for a philosophical debate obfuscated by the recurrent myth about the monster of Malmesbury. Once done that, I offer setting the bases of a metodological aproach which stars from this notion of resistance. Thus, I would back the first step towards a contemporary appropriation ?or expropriation? of the obedience-security relationship within the Hobbesian matrix.

  13. O historiador e o teórico: a historiografia de Hobbes na teoria das relações internacionais The historian and the theoretician: Hobbes' historiography in the theory of international relations

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    Soraya Nour

    2003-12-01

    Full Text Available Uma dificuldade crucial no estudo das relações internacionais é unir investigação teórica com investigação histórica. O objetivo deste artigo é analisar como Hobbes enfrentou este problema, bem como em que medida a solução que apresentou influenciou a teoria das relações internacionais e permite ainda hoje resolver dificuldades desta disciplina. A primeira parte examina como Hobbes justifica seu método de pensar histórica e teoricamente ao mesmo tempo. A segunda parte mostra como Hobbes é recuperado no pós-Segunda Guerra tanto pela revisão do programa idealista como pelo emergente realismo, em ambos os casos a fim de criticar o idealismo do entreguerras. A terceira parte, tendo em vista o debate contemporâneo em relações internacionais, mostra como o neo-realismo, concentrando-se em tecnologias de poder, perde o interesse pela investigação histórica presente no realismo clássico; e o normativismo que se fortalece a partir dos anos 90, formulando uma justificada crítica à ausência de reflexão ética no neorealismo, recai muitas vezes em variantes do idealismo utópico. Em ambos há um déficit de investigação histórica, o que não permite analisar a contingência das relações sociais. Se o caráter predominantemente antropológico da historiografia de Hobbes, bem como o caráter predominantemente institucionalista de sua teoria do Estado e do Direito não podem mais ser aceitos, é seu modo de pensar ao mesmo tempo teórica e historicamente o legado e o desafio que nos deixa.A crucial issue in international relations is to associate theoretical with historical inquiry. This paper aims to analyse how Hobbes struggled with this problem, in which measure his answers have influenced the theory of international relations and to what extent they permit the solution of contemporary problems in this discipline. The first part analyses how Hobbes justifies his method of thinking both historically and theoretically. The

  14. Razão, história e justificação da lei civil segundo Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Wladimir Barreto Lisboa

    2008-09-01

    Full Text Available O autor procura analisar a relação existenteentre lei natural e lei civil em Thomas Hobbes.Para isso analisa sua crítica à história e ao commonlaw enquanto incapazes de fundar a racionalidadedo poder civil. Mostra-se igualmente de que modoo poder soberano encontra seu fundamento nas leismorais. Por fim, indica-se como a igualdade de direitos,tal como pensada na modernidade, sobretudoem Hobbes, parece inviabilizar a idéia de direitoscujos titulares seriam grupos e não indivíduos.Abstract: The author analyzes the relationbetween natural law and civil law in ThomasHobbes, pointing out Hobbes’ argument thatneither history or common law are able to foundcivil’s power rationality. The article shows, aswell, how sovereign power is founded by themoral law and how the equality of rights inHobbes seems to undermine the idea that ispossible for groups to be subject of rights insteadindividuals.

  15. Huntington's disease presenting as amyotrophic lateral sclerosis.

    LENUS (Irish Health Repository)

    Phukan, Julie

    2010-08-01

    We present the clinical, electrophysiological and molecular genetic findings of a 58-year-old male with genetically confirmed Huntington\\'s disease (HD) and concurrent clinically definite ALS by El Escorial criteria. The patient presented with asymmetric upper limb amyotrophy and weakness, and subsequently developed chorea and cognitive change. Genetic testing confirmed the presence of expanded trinucleotide repeats in huntingtin, consistent with a diagnosis of Huntington\\'s disease. This case confirms the rare coexistence of Huntington\\'s disease and motor neuron degeneration.

  16. Between Hobbes and Spinoza. Research on the Philosophical Matrix of Ferdinand Tönnies’ Sociological Categories

    Directory of Open Access Journals (Sweden)

    Furio Ferraresi

    2017-07-01

    Full Text Available This essay reconstructs the main lines of Ferdinand Tönnies’ (1855-1936 critical approach to the thought of Hobbes and Spinoza. Specifically it shows the role played by the two philosophers in developing the categories of community (Spinoza and society (Hobbes. From the stand point of political thought, the essay reveals how Tönnies’ on going interpretation of Hobbes focuses more and more on the constitutive moment of the modern form of State. In this area it draws on Spinoza’s reflections on democracy as an absolutum omnino imperium. Tönnies is thus able to distinguish conceptually between the Hobbesian State, as a “society” that absorbs all natural law, and its natural law origin (the «original assembly», where we find a “common” element that can never be entirely neutralized by the State.

  17. Perceptions of genetic discrimination among people at risk for Huntington?s disease: a cross sectional survey

    OpenAIRE

    Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R

    2009-01-01

    Objective To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington?s disease who had undergone genetic testing or remained untested. Design Cross sectional, self reported survey. Setting Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. Participants 233 genetically tested and untested asymptomatic people at risk for Huntington?s disease (response rate 80%): 167 underwent testing (83 had the Huntingt...

  18. Comment Hobbes tente de rendre son matérialisme acceptable dans les appendices du Léviathan

    Directory of Open Access Journals (Sweden)

    Anne Staquet

    2011-11-01

    Full Text Available Le Léviathan de Hobbes [1651] a subi de nombreuses attaques, au point qu’il est jugé responsable de la grande peste de 1665 et de l’incendie de Londres l’année suivante et que le parlement ouvre une procédure contre l’ouvrage. Aussi, lorsqu’en 1666, Thomas Hobbes veut publier la traduction latine de ce livre, il y adjoint trois appendices. La version latine de l’œuvre est généralement jugée plus acceptable que le texte originaire anglais. En étudiant la manière dont Hobbes traite de son matérialisme dans ces appendices, je tente de montrer que les addenda latins ne constituent en aucune manière un retour en arrière du texte, mais que le philosophe enrobe simplement davantage des propos que, par ailleurs, il rend plus radicaux.Hobbes’s Leviathan [1651] has been critiqued so much that it was held responsible for the Great Plague of 1665 and the Fire of London during the following year, resulting in the Parliament instituting proceedings against the book. Therefore, when in 1666 Thomas Hobbes wanted to publish a Latin translation of this book, he added three appendices. Generally, the Latin version of the work is considered more acceptable than the English original text. By studying how Hobbes deals with his materialism in these appendices, I try to show that the Latin additions are in no way a reversal of the text, but that the philosopher simply veiled more propositions, while at the same time making them more radical.

  19. Psychopathology in Huntington's disease

    NARCIS (Netherlands)

    Duijn, Erik van

    2010-01-01

    Dit proefschrift begint met een overzichtsartikel van oorspronkelijke onderzoek naar psychopathologie bij mutatiedragers voor de ziekte van Huntington. Aansluitend worden de resultaten van een cohortstudie naar de aanwezigheid en ernst van psychopathologie bij mensen met de ziekte van Huntington in

  20. Human Nature and Social Order: A Comparative Critique of Hobbes ...

    African Journals Online (AJOL)

    Central to most intellectual debates on political organization is the issue of human nature, for one's understanding of it influences one's prescriptions on how best society can be governed. This paper examines the contractarian theories of Hobbes and Locke in their attempts to identify the conditions for social order.

  1. Liberdade, lei natural e direito natural em Hobbes: limiar do direito e da política na modernidade Freedom, natural law and natural right in Hobbes: threshold of law and politics in modernity

    Directory of Open Access Journals (Sweden)

    Natalia Maruyama

    2009-01-01

    Full Text Available Liberdade e poder são dois temas que se correlacionam ao longo da história da filosofia política moderna. Nos textos de Hobbes, a ideia da liberdade como ausência de impedimentos às ações ajuda-nos a pensar o dever de obediência ao poder soberano e as relações entre política e direito. Uma situação de vácuo jurídico, em que tudo é permitido, faz-se, contudo, impossível, de modo que a solução de Hobbes consiste em sustentar a ideia do direito natural como direito originário individual vinculado à preservação da vida. Suas ideias do direito natural e da lei natural, que servem de fundamento ao dever de obediência ao soberano, amparam-se em princípios jurídicos, teológicos e biológicos. Tais princípios, entretanto, não dão conta da questão da extensão do poder soberano. Hobbes recorre à análise da linguagem. Sua teoria contratual afirma o princípio de preservação da vida na base da política e sustenta a ideia da criação e da manutenção do poder soberano no ato de linguagem implicado na estrutura representativa do pacto político.Liberty and power are two subjects correlated along the history of the political modern philosophy. In the texts of Hobbes, the idea of liberty as absence of impediments to the actions helps us to think the duty of obedience to the sovereign power and the relations between politics and right. A situation of legal vacuum, in which everything is allowed, is, nevertheless, impossible, so that the solution of Hobbes consists in supporting the idea of the natural right like original individual right linked to the preservation of the life. His ideas of the natural right and of the natural law, which serve of basis to the duty of obedience to a sovereign, lean on legal, theological and biological principles. In spite of that, such principles do not surround the question of the extension of the sovereign power. Hobbes resorts to the analysis of the language. His contractual theory affirms

  2. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

    DEFF Research Database (Denmark)

    Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

    2013-01-01

    Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

  3. VT Data - Zoning 20120709, Huntington

    Data.gov (United States)

    Vermont Center for Geographic Information — Zoning district data for the Town of Huntington, Vermont. For details regarding each zoning district refer to the current zoning regulations on town of Huntington's...

  4. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. L’analyse des passions dans la dissolution du corps politique : Spinoza et Hobbes

    Directory of Open Access Journals (Sweden)

    Julie Saada-Gendron

    2005-09-01

    Full Text Available Les théories contractualistes de l’âge classique se fondent sur la conception d’un état de nature qui devient, à cause de ses contradictions internes, un état de guerre auquel il faut remédier par un artifice rationnel, le pacte. Alors même que ces contradictions sont issues des passions humaines, celles-ci semblent impensables dans le cadre purement juridique de ces théories, où ne sont analysés ni les mécanismes passionnels d’adhésion au politique, ni la menace de dissolution de l’État. Nous nous attachons à comparer le rôle que Hobbes et Spinoza font jouer aux passions dans l’élaboration de leurs doctrines politiques : tandis que Hobbes témoigne d’un souci constant des passions, tout en les mettant à l’écart lorsqu’il s’agit de penser la construction et le fonctionnement de l’édifice politique, Spinoza permet de penser deux groupes de passions – celles qui résistent nécessairement au corps politique et celles qui lui font obstacle ponctuellement. Ces dernières constituent tout à la fois des facteurs de décomposition et de recomposition du corps collectif. Cette approche du politique à partir des causes de sa dissolution permet d’apporter un éclairage à la signification du droit naturel moderne tel qu’il se construit chez Hobbes et chez Spinoza.The contractualist theories of the Classical Age are grounded on the conception of a state of nature which becomes, because of its internal contradictions, a state of war to which the only remedy is a rational artifice : the pact. Although these contradictions arise from human passions, passions seem to be unthinkable in the strictly juridical frame of these theories, where neither the passional mechanisms of political adhesion, nor the menace of the dissolution of the State, are analysed. We will strive to compare the role that Hobbes and Spinoza attribute to passions in their respective political doctrines. Whereas Hobbes shows a constant

  6. Electronic Transport in Single-Stranded DNA Molecule Related to Huntington's Disease

    Science.gov (United States)

    Sarmento, R. G.; Silva, R. N. O.; Madeira, M. P.; Frazão, N. F.; Sousa, J. O.; Macedo-Filho, A.

    2018-04-01

    We report a numerical analysis of the electronic transport in single chain DNA molecule consisting of 182 nucleotides. The DNA chains studied were extracted from a segment of the human chromosome 4p16.3, which were modified by expansion of CAG (cytosine-adenine-guanine) triplet repeats to mimics Huntington's disease. The mutated DNA chains were connected between two platinum electrodes to analyze the relationship between charge propagation in the molecule and Huntington's disease. The computations were performed within a tight-binding model, together with a transfer matrix technique, to investigate the current-voltage (I-V) of 23 types of DNA sequence and compare them with the distributions of the related CAG repeat numbers with the disease. All DNA sequences studied have a characteristic behavior of a semiconductor. In addition, the results showed a direct correlation between the current-voltage curves and the distributions of the CAG repeat numbers, suggesting possible applications in the development of DNA-based biosensors for molecular diagnostics.

  7. Clinical presentation of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Ruocco Heloísa H.

    2006-01-01

    Full Text Available OBJECTIVE: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. METHOD: All patients were interviewed following a structured clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG repeat in the Huntington Disease gene. High resolution brain MRI was performed in all patients. RESULTS: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our Neurogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001 and reduced cerebral and cerebellum volumes (p=0.01. CONCLUSION: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were seizures and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.

  8. Hobbes Y Kant: De La Guerra Entre Los Individuos A La Guerra Entre Los Estados

    Directory of Open Access Journals (Sweden)

    Adelino Braz

    2003-10-01

    Full Text Available The article takes the Kantian criticism to the political thought of Hobbes. It explains in the first place the logic of the desire of power in Hobbes and how this conducts to a state of war, or state of nature, that only can be finish under the threat of a sovereign, that receives from all the members of a community the right to defend them from others. Subsequently it explains the critics done by Kant to the hobbesian formulation of the state of nature, where it is assumed that just the establishment of the civil state, is sufficient to end to the state of war.

  9. Libertad negativa como estrategia deconstructora de deseos y temores en el materialismo antropológico de Hobbes

    Directory of Open Access Journals (Sweden)

    Francisco Javier Higuero

    2015-01-01

    Full Text Available Thomas Hobbes explica en Leviathan que el estado de naturaleza, privado de gobierno, de instituciones políticas o sociales, de leyes y hasta de contratos legalmente establecidos, otorga libertad absoluta a los individuos, al tiempo que los condena a una guerra perpetua entre ellos, que se ven obligados a vivir siempre con gran inseguridad y miedo a una muerte violenta. Dicho pensador enumera diversas razones por las que los seres humanos llegan a sentir enemistad entre sí en el estado de naturaleza, entre las que incluye los conflictos que proceden del apetito incontrolable por poseer los bienes que no pueden ser divididos o disfrutados de común acuerdo. Mediante el uso de la fuerza, se decide que tales bienes sean poseídos por los más fuertes. Ahora bien, la igualdad existente entre los hombres para matarse mutuamente provoca un sentimiento de miedo que llega a sustituir la inclinación dirigida a prevalecer, de un modo u otro. En tales circunstancias, Hobbes parece pronunciarse a favor de una libertad negativa que, de hecho, deconstruiría la dicotomía binaria formada por la pugna existente entre deseos y temores. In Leviathan, Thomas Hobbes implies that the state of nature, devoid of government, political or social institutions, laws, or legally enforceable agreements, allows absolute freedom to individuals at the same time that condemns them to perpetual war with each other, so that they were compelled to live all the time with insecurity and fear of a violent death. Hobbes enumerates a variety of reasons of why men are at enmity with each other in the state of nature, they include the conflicts that are the result from the appetite for the things that cannot be divided or enjoyed in common. By the use of force, it is decided that those goods go to the strongest one. Now then, the equality of men with respect to their ability to kill each other creates fear among them. In order to resolve the binary dichotomy expressed in the

  10. Hobbes, la coopération et la théorie des jeux

    Directory of Open Access Journals (Sweden)

    Marc Parmentier

    2010-04-01

    Full Text Available L'objectif de cet article est d'établir dans quelle mesure la théorie des jeux permet de formaliser et d'éclairer trois problématiques-clés de la philosophie politique de Hobbes : la guerre de tous contre tous dans l'état de nature ; le pacte instaurant un souverain absolu ; le mode d'action de ce dernier pour faire respecter les contrats au sein de l'état civil. L'analyse révèle qu'à certains égards le « problème de confiance » formulé par Amartya Sen apparaît plus pertinent que le célèbre « dilemme du prisonnier » évoqué par de nombreux commentateurs. Elle révèle également les ambiguïtés d'une œuvre susceptible de plusieurs modélisations et de plusieurs jugements possibles quant à la place de son auteur dans l'histoire du libéralisme.This article aims to establish whether the theory of games can formalise and explain three basic issues raised by Hobbes: the war of all against all in the state of nature; the social contract that establish absolute sovereignty; legitimate means at the sovereign’s disposal to impose people’s consent to abide by the rules of the social contract. It will be argued that the « assurance problem » formulated by Amartya Sen appears more relevant than the well-known « prisoner's dilemma » in some respects. Our analysis also reveals some ambiguities in Hobbes' political philosophy that may lead to diverse interpretations and judgments about his role in the history of liberalism.

  11. The political philosophy of Hobbes and the absolutist state

    OpenAIRE

    Souza, Sharon Cristine Ferreira de; Oliveira, Thiago Vieira Mathias de

    2009-01-01

    Desenvolve-se uma análise trazendo, principalmente, um apanhado histórico e uma descrição sistemática a respeito da vida e obra do contratualista Thomas Hobbes, bem como sua filosofia, suas influências, delineando o porquê das concepções e conceitos trazidos em seus escritos, seus objetivos e como o Absolutismo, na posteridade, desemboca no modelo de Estado Liberal, com a sede por direitos individuais observadas na crescente burguesia. The paper develops an analysis bringing primarily a hi...

  12. Huntington's disease: a perplexing neurological disease ...

    African Journals Online (AJOL)

    Huntington's disease is an inherited intricate brain illness. It is a neurodegenerative, insidious disorder; the onset of the disease is very late to diagnose. It is caused by an expanded CAG repeat in the Huntingtin gene, which encodes an abnormally long polyglutamine repeat in the Huntingtin protein. Huntington's disease ...

  13. Hobbes, les pirates et les corsaires. Le « Léviathan échoué » selon Carl Schmitt

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    Dominique Weber

    2005-04-01

    Full Text Available Parmi les nombreux problèmes que pose l’ouvrage de Carl Schmitt Le Léviathan dans la doctrine de l’État de Thomas Hobbes, il en est un, majeur, qui concerne l’utilisation de la « mythologie politique » pour expliquer la réalité ou les doctrines politiques. Il y a là, à n’en pas douter, l’expression de l’un des versants de l’irrationalisme de Schmitt. La thèse de l’auteur est très claire : parce que Hobbes ne possédait aucun « sens mythologique », il s’est trompé de monstre biblique, appelant Leviathan son traité consacré au pouvoir d’État, alors qu’il aurait dû l’appeler plus adéquatement Behemoth, manquant du coup la Meeresbild caractérisant l’Angleterre de son temps. La thèse peut paraître séduisante, elle s’appuie néanmoins sur un présupposé fort contestable, car Hobbes ne vise nullement à créer des mythes. Il s’agit donc d’interroger la théorisation hobbesienne de la piraterie, d’une part, et de la dissidence religieuse « sauvage », d’autre part, afin de montrer que le choix par Hobbes des monstres du Livre de Job est un choix rationnellement assumé.

  14. Teoria da motivação humana na filosofia natural de Hobbe

    Directory of Open Access Journals (Sweden)

    Cláudio Leivas

    2007-01-01

    Full Text Available Compreender de forma clara e sucinta como a teoria da sensação de Hobbes articula e engendra sua teoria da motivação, essa constituída pelas afecções (paixões, deliberação, vontade e ação, é o que pretendemos com o presente estudo.

  15. De vuelta a Hobbes

    Directory of Open Access Journals (Sweden)

    Wilmar Martínez Márquez

    2013-12-01

    Full Text Available El propósito de este artículo es mostrar que el Estado constituye la forma más idónea para resolver las amenazas de inseguridad y guerra que acosan las sociedades contemporáneas. Para sustentar este planteamiento, en el artículo se rescatan varios de los elementos centrales de la teoría política de Thomas Hobbes y se precisa cómo estos pueden servir, en primera instancia, de criterios de explicación y diagnóstico de dichas amenazas, y en un segundo momento, de pautas para enfrentarlas. Resalta especialmente el concepto de soberanía y los debates que han surgido recientemente alrededor de este autor. Finalmente, se concluye que el mantenimiento de esta figura -la soberanía- va a ser esencial para garantizar el orden en la época actual. El método de investigación es el análisis documental. A partir de la identificación de categorías políticas relevantes se pasa a dar cuenta del estado de cosas correspondiente.

  16. De vuelta a Hobbes

    Directory of Open Access Journals (Sweden)

    Wilmar Martínez Márquez

    2013-01-01

    Full Text Available El propósito de este artículo es mostrar que el Estado constituye la forma más idónea para resolver las amenazas de inseguridad y guerra que acosan las sociedades contemporáneas. Para sustentar este planteamiento, en el artículo se rescatan varios de los elementos centrales de la teoría política de Thomas Hobbes y se precisa cómo estos pueden servir, en primera instancia, de criterios de explicación y diagnóstico de dichas amenazas, y en un segundo momento, de pautas para enfrentarlas. Resalta especialmente el concepto de soberanía y los debates que han surgido recientemente alrededor de este autor. Finalmente, se concluye que el mantenimiento de esta figura —la soberanía— va a ser esencial para garantizar el orden en la época actual. El método de investigación es el análisis documental. A partir de la identificación de categorías políticas relevantes se pasa a dar cuenta del estado de cosas correspondiente.

  17. Huntington's disease : Psychological aspects of predictive testing

    NARCIS (Netherlands)

    Timman, Reinier

    2005-01-01

    Predictive testing for Huntington's disease appears to have long lasting psychological effects. The predictive test for Huntington's disease (HD), a hereditary disease of the nervous system, was introduced in the Netherlands in the late eighties. As adverse consequences of the test were

  18. O lugar da filosofia civil e a classificação das ciências segundo Hobbes

    Directory of Open Access Journals (Sweden)

    Delmo Mattos

    2010-09-01

    Full Text Available A filosofia civil ocupa um lugar de destaque no sistema filosófico de Hobbes. Compreende a sua reflexáo das disposições e costumes dos homens, isto é, a ética, os deveres civis e a política. No entanto, a filosofia civil constitui apenas uma parte da elaboraçáo sistemática da filosofia hobbesiana, que contêm, além da sua reflexáo política, importantes apontamentos sobre a física e a geometria. Neste artigo, buscaremos examinar o modo como Hobbes posiciona as diferentes partes que compõem o seu sistema filosófico, a fim de tornarmos explícito o lugar que a filosofia civil ocupa no seu empreendimento filosófico.

  19. Identification of genetic variants associated with Huntington's disease progression

    DEFF Research Database (Denmark)

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

    2017-01-01

    indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression......BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...

  20. Huntington's disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia

    2011-01-01

    In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...

  1. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington?s Disease Mouse Model R6/2

    OpenAIRE

    Nielsen, Signe Marie Borch; Hasholt, Lis; N?rrem?lle, Anne; Josefsen, Knud

    2015-01-01

    Huntington?s disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indic...

  2. GUERRA E PAZ NA TEORIA POLÍTICA DE THOMAS HOBBES

    Directory of Open Access Journals (Sweden)

    Lígia Pavan Baptista

    2014-08-01

    Full Text Available Este artigo tem o objetivo de analisar em que medida a teoria política moderna, tal como apresentada por Thomas Hobbes, expondo um novo paradigma na análise de questões como a origem do Estado e do poder político, assim como, definindo, por meio de metodologia científica, conceitos tais como guerra, paz, soberania, justiça, igualdade e liberdade, podem estabelecer as raízes de questões das relações internacionais, apesar de não ser o principal objetivo do autor.

  3. Arendt on Hobbes as the true philosopher of the bourgeoisie

    Directory of Open Access Journals (Sweden)

    Adriano Correia

    2015-07-01

    Full Text Available In The Origins of Totalitarianism, when examine the elements and origins of total domination, Hannah Arendt devotes special attention to the political emancipation of the bourgeoisie. For Arendt imperialism is the truth of the bourgeois understanding of politics, according to which politics should not be more than a well-organized police force. The truth of bourgeois politics is the reduction of politics to mere force. Our purpose is to reconstruct this movement from the vantage point of arendtian appropriation of Hobbes, "the true philosopher of the bourgeoisie."

  4. «I speak generally of Law». Law, Laws and Courts in the Dialogue of Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Mario Piccinini

    2014-12-01

    Full Text Available Analyzing the Dialogue between a Philosopher and a Student of the Common Laws of England by Thomas Hobbes, the essay traces the historical tradition and the reasons for its secular underestimation. The Hobbesian text is placed within the history of English law and the controversies that accompanied and followed the revolution of 1640. It is then compared with the political works of Hobbes, showing how the silence of the law is gradually replacing the state of nature as image of the death of the Commonwealth. The Dialogue proves to be a firm position in favor of an universal and equal capacity to understand what the law is. This latter is the product of the will of a sovereign, who however is the institutionalization of the authorization of the individuals who constitute it.

  5. Learning about Huntington's Disease

    Science.gov (United States)

    Skip to main content Learning About Huntington's Disease Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  6. Changes in mental state and behaviour in Huntington's disease.

    Science.gov (United States)

    Eddy, Clare M; Parkinson, Ellice G; Rickards, Hugh E

    2016-11-01

    Changes in mental state and behaviour have been acknowledged in Huntington's disease since the original monograph in 1872 provided evidence of disinhibition and impaired social cognition. Behavioural problems can manifest before obvious motor symptoms and are frequently the most disabling part of the illness. Although pharmacological treatments are used routinely for psychiatric difficulties in Huntington's disease, the scientific evidence base for their use is somewhat sparse. Moreover, effective treatments for apathy and cognitive decline do not currently exist. Understanding the social cognitive impairments associated with Huntington's disease can assist management, but related therapeutic interventions are needed. Future research should aim to design rating scales for behaviour and mental state in Huntington's disease that can detect change in clinical trials. Generally, communication and understanding of behaviour and mental state in Huntington's would be enhanced by a clear conceptual framework that unifies ideas around movement, cognition, emotion, behaviour, and mental state, reflecting both the experience of the patient and their underlying neuropathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Hobbes and Selfish Morality in the State of Nature

    Directory of Open Access Journals (Sweden)

    Maximiliano Martínez

    2008-04-01

    Full Text Available In this paper I explore the controversial claim that morality exists in the Hobbesian state of nature (represented in the rationality and prudence of natural laws, and how this moral is a necessary condition to achieve civil state. In order to accomplish this objective, I examine the work of G. Kavka on this topic, while analizing Hobbes's “reply to the fool”, using game theory. I propose, at the end of this paper, the necessity and justification of going from one state to another, emphasizing on the precariety of morality in the state of nature to guarantee the fulfilment of the natural laws.

  8. A Metabolic Study of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Rajasree Nambron

    Full Text Available Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III and controls.Control (n = 15, premanifest (n = 14 and stage II/III (n = 13 participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a, fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine there is a suggestion (p values between 0.02 and 0.05 that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that

  9. O desenvolvimento político em Huntington e Fukuyama Huntington and Fukuyama on political development

    Directory of Open Access Journals (Sweden)

    Natália Nóbrega de Mello

    2010-01-01

    Full Text Available O artigo contrasta as teses de Huntington e Fukuyama sobre desenvolvimento político. As obras analisadas, Ordem política nas sociedades em mudança e O fim da história, inscrevem-se entre duas conjunturas decisivas - 1968 e 1989. Huntington desmontou a equivalência entre desenvolvimento político e modernização e Fukuyama reafirmou a democracia como o destino de todos os países e, desse modo, como o fim da história. Nesta comparação, dois eixos se sobressaem: o contexto de produção das obras e a alternância entre os polos teóricos da democracia e da estabilidade. Procura-se demonstrar como, apesar de reinserir a democracia no desenvolvimento político, a instabilidade continua a ser um foco privilegiado de análise no pensamento de Fukuyama.The article contrasts the theories of Huntington and Fukuyama on political development. The analyzed works, Political order in changing societies and The end of history, fall between two decisive historical moments - in 1968 and 1989. Huntington disassembled the equivalence between political development and modernization; Fukuyama reaffirmed democracy as the destiny of all countries and, as such, it is the end of history. In this comparison, two axes call our attention: the production context of these works and the alternation between the theoreticals poles of democracy and stability. The article shows how, although reenters democracy in the political development theory, instablility remains a prime focus of analysis in Fukuyama's thought.

  10. Mapping energy poverty in Huntington, West Virginia

    Science.gov (United States)

    Callicoat, Elizabeth Anne

    Energy poverty is a growing phenomenon culminating from the combination of low to mid household income, deteriorating housing structures and rising household energy costs. Energy prices are increasing for all households, but the burden is proportionally larger for those with low to mid income. These groups must sacrifice to afford energy, and are often unable or do not have the autonomy to make structural improvements, especially if they rent their home. Data on residential dwellings from the Cabell County Tax Assessor's Office was used within a geographic information system to map where energy poverty likely exists within the city limits of Huntington, WV. It was found that one fifth of Huntington households are at a high risk of energy poverty, primarily located across the northern section of the city and in the center, surrounding Marshall University, Downtown and Cabell Huntington Hospital.

  11. Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease

    DEFF Research Database (Denmark)

    Dale, Maria; Maltby, John; Shimozaki, Steve

    2016-01-01

    OBJECTIVE: Depression and anxiety significantly affect morbidity in Huntington's disease. Mice. models of Huntington's disease have identified sex differences in mood-like behaviours that vary across disease lifespan, but this interaction has not previously been explored in humans with Huntington......'s disease. However, among certain medical populations, evidence of sex differences in mood across various disease stages has been found, reflecting trends among the general population that women tend to experience anxiety and depression 1.5 to 2 times more than men. The current study examined whether...... disease stage and sex, either separately or as an interaction term, predicted anxiety and depression in Huntington's disease. METHODS: A cross-sectional study of REGISTRY data involving 453 Huntington's disease participants from 12 European countries was undertaken using the Hospital Anxiety...

  12. Huntington disease: a case study of early onset presenting as depression.

    Science.gov (United States)

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-10-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and rigidity, is reported. Meanwhile, the father developed the adult variant of Huntington disease. The boy's diagnosis was confirmed by molecular genetic analysis and magnetic resonance imaging. It is important to be aware of hereditary conditions such as Huntington disease and to provide family counseling before genetic testing and after the diagnosis is confirmed.

  13. Factor analysis of the hospital anxiety and depression scale among a Huntington's disease population

    DEFF Research Database (Denmark)

    Dale, Maria; Maltby, John; Martucci, Rossana

    2015-01-01

    INTRODUCTION: Depression and anxiety are common in Huntington's disease, a genetic neurodegenerative disorder. There is a need for measurement tools of mood to be validated within a Huntington's disease population. The current study aimed to analyze the factor structure of the Hospital Anxiety...... and Depression Scale in Huntington's disease. METHODS: Data from the European Huntington's Disease Network study REGISTRY 3 were used to undertake a factor analysis of the scale among a sample of 492 Huntington's disease mutation carriers. The sample was randomly divided into two equal subsamples...... support for an eight-item version of the scale to be used as a measure of general distress within Huntington's disease populations. © 2015 International Parkinson and Movement Disorder Society....

  14. PSYCHIATRIC ASPECTS OF HUNTINGTON DISEASE – CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Mirela Batta

    2004-04-01

    Full Text Available Background. Huntington disease occurrs rarely, it can be encountered not only by neurologists and psychiatrists but also by other medical practitioners. Its characteristic features are involuntary movements, cognitive disorders and gradual development of dementia. Diagnosis is given on the basis of these clinical features, positive familial anamnesis, with the laboratory exclusion of other neuropsychiatric diseases and with the help of neuroimaging methods (in particular NMR. The disease can be only confirmed by means of genetic analysis.Patients and methods. In this article, four cases of patients with Huntington disease and diverse psychiatric disorders that were hospitalised at the psychiatric department of the Maribor General Hospital between October 2002 and March 2003 are described. All the patients fulfilled the valid criteria for the diagnosis of Huntington disease. However, they differed according to their accompanying psychiatric psychopathology, age and social problems.Conclusions. The purpose of this article is to draw attention to different psychiatric symptoms and clinical manifestations of Huntington disease that are often misleading in the diagnostic process. In addition, exigency of early diagnostics, guidelines for referrals to genetic testing and psychiatric monitoring of these patients are emphasised.

  15. Green leviathan? Thomas hobbes, joel bakan and Arnold schwarzenegger.

    Science.gov (United States)

    Evans, Robert G

    2007-02-01

    Thomas Hobbes postulates that men are driven by "a perpetual and restless desire of power after power, that ceaseth only in death." The miserable consequences of this drive for power and the competing "desire of ease and sensual delight" and "fear of death and wounds" lead them to establish and obey. Substituting "profit" for "power" yields a description of the modern corporation, but without the desires or fears of natural persons. Such "unnatural persons" lack the Hobbesian ground of obligation, yet have appropriated the privileges and protections of natural persons. They challenge or undermine the sovereign wherever it limits their profits. Governor Schwarzenegger's re-election in California, however, on a strong anti-CO(2) program, suggests a willingness by threatened natural persons to re-empower Leviathan.

  16. Semantic, phonologic, and verb fluency in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Jardim Azambuja

    Full Text Available Abstract Verbal fluency tasks have been identified as important indicators of executive functioning impairment in patients with frontal lobe dysfunction. Although the usual evaluation of this ability considers phonologic and semantic criteria, there is some evidence that fluency of verbs would be more sensitive in disclosing frontostriatal physiopathology since frontal regions primarily mediate retrieval of verbs. Huntington's disease usually affects these circuitries. Objective: To compare three types of verbal fluency task in the assessment of frontal-striatal dysfunction in HD subjects. Methods: We studied 26 Huntington's disease subjects, divided into two subgroups: mild (11 and moderate (15 along with 26 normal volunteers matched for age, gender and schooling, for three types of verbal fluency: phonologic fluency (F-A-S, semantic fluency and fluency of verbs. Results: Huntington's disease subjects showed a significant reduction in the number of words correctly generated in the three tasks when compared to the normal group. Both controls and Huntington's disease subjects showed a similar pattern of decreasing task performance with the greatest number of words being generated by semantic elicitation followed by verbs and lastly phonologic criteria. We did not find greater production of verbs compared with F-A-S and semantic conditions. Moreover, the fluency of verbs distinguished only the moderate group from controls. Conclusion: Our results indicated that phonologic and semantic fluency can be used to evaluate executive functioning, proving more sensitive than verb fluency. However, it is important to point out that the diverse presentations of Huntington's disease means that an extended sample is necessary for more consistent analysis of this issue.

  17. Major Superficial White Matter Abnormalities in Huntington's Disease

    Science.gov (United States)

    Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

    2016-01-01

    Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

  18. Did the "Woman in the Attic" in Jane Eyre Have Huntington Disease?

    Science.gov (United States)

    Coon, Elizabeth A; Hassan, Anhar

    2015-01-01

    References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Our aim was to compare Charlotte Brontë's depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington's original essay "On chorea" with the hypothesis that Mason was displaying features of Huntington disease. Charlotte Brontë's 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington's tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Brontë's character had features of Huntington disease as originally described by Huntington. Brontë's keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era.

  19. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  20. Continuity and Discontinuity, Change and Duration: Hobbes' Riddle of the Theseus and the Diversity of Historical Logics.

    Science.gov (United States)

    Blum, Mark E.

    1996-01-01

    Reiterates the need for an understanding of the concepts of continuity and change, not simply in the representation of historical events, but in the writing and study of history. Uses Thomas Hobbes's riddle of Theseus to illustrate the need for multiple readings and critical analysis in history instruction. (MJP)

  1. High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal

    LENUS (Irish Health Repository)

    Kilbride, Sean M

    2011-07-26

    Abstract Background The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington\\'s disease and Alzheimer\\'s disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal. Results Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca2+-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased. Conclusions These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.

  2. aliving with Huntington´s disease in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Baxa, Monika

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 6-6 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] Institutional support: RVO:67985904 Keywords : Czech Huntington Association * life with Huntington ´ disease Subject RIV: FH - Neurology

  3. Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

    Science.gov (United States)

    Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

    2012-04-01

    Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

  4. Psychiatric symptoms and CAG expansion in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

    1996-02-16

    The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

  5. Clinical and genetic data of Huntington disease in Moroccan patients

    African Journals Online (AJOL)

    Background: Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10 /100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Methods: Clinical ...

  6. A posição original como mediação entre estado de natureza e imperativo categórico: Rawls entre Hobbes e Kant

    Directory of Open Access Journals (Sweden)

    Delamar José Volpato Dutra

    2014-06-01

    Full Text Available http://dx.doi.org/10.5007/1677-2954.2014v13n1p112 O texto apresenta o conceito de lei natural em Hobbes e contesta que o conteúdo da mesma seja exclusivamente um imperativo hipotético decorrente da racionalidade estratégica. Aproveita a interpretação de Rawls para conferir um estatuto moral ao conteúdo das leis naturais, tais quais elas foram propostas por Hobbes. Para tal intento, a posição original é lida como uma estratégia de contaminação do imperativo categórico por imperativos hipotéticos. Se Kant afirma que, com várias limitações, a regra de ouro pode ser derivada do imperativo categórico, então, deve haver algum elemento da regra de outro no imperativo categórico. O texto perscruta qual seria esse elemento. O presente artigo apresenta, portanto, uma leitura de Hobbes inspirada na posição original de Rawls, cuja finalidade será mostrar que as interpretações morais de Hobbes sustentadas, por exemplo, por Taylor, Warrender, Rawls e Habermas, são defensáveis, muito embora não pelas razões alegadas por alguns deles. Conclui-se estar em questão, destarte, não uma discordância quanto aos conteúdos do que se poderia chamar justiça ou regras de convivência, mas quanto às estratégias de fundamentação.

  7. 75 FR 13454 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

    Science.gov (United States)

    2010-03-22

    ...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water Championships. The..., ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' (Docket number USCG...

  8. 75 FR 38710 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

    Science.gov (United States)

    2010-07-06

    ...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... Regulation on the navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water... ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' in the Federal...

  9. Earliest functional declines in Huntington disease

    Science.gov (United States)

    Beglinger, Leigh J.; O'Rourke, Justin J.F.; Wang, Chiachi; Langbehn, Douglas R.; Duff, Kevin; Paulsen, Jane S.

    2013-01-01

    We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDRS Total Functional Capacity (TFC) and Functional Assessment Scale (FAS), we examined participants from Huntington Study Group clinics who were not diagnosed at their baseline visit but were diagnosed at a later visit (N = 265). Occupational decline was the most common with 65.1% (TFC) and 55.6% (FAS) reporting some loss of ability to engage in their typical work. Inability to manage finances independently (TFC 49.2%, FAS 35.1%) and drive safely (FAS 33.5%) were also found. Functional decline was significantly predicted by motor, cognitive, and depressive symptoms. The UHDRS captured early functional losses in individuals with HD prior to formal diagnosis, however, fruitful areas for expanded assessment of early functional changes are performance at work, ability to manage finances, and driving. These are also important areas for clinical monitoring and treatment planning as up to 65% experienced loss in at least one area prior to diagnosis. PMID:20471695

  10. Hobbes y la teoría del Estado moderno. La lectura de Bobbio

    Directory of Open Access Journals (Sweden)

    Vitale, Ermanno

    2007-06-01

    Full Text Available This article gives an account of Thomas Hobbes’s two main legacies to the modern political thought, in the reading that Noberto Bobbio has given in many of his works. The first one is a methodological legacy, which consists in the priority of the demonstratio over any kind of interpretatio. The second is individualism, whose different dimensions are decisive to justify, to compare, and to judge the wide range of political formulae that the Leviathan, as nature of the modern State, can hold. The article ends with a third level of comparison of the opposite fortune of Hobbes’s and Bobbio’s works in their times and ours.

    Este trabajo está dedicado al análisis de dos legados fundamentales de Thomas Hobbes al pensamiento político moderno, en la lectura que de ello ha ofrecido Norberto Bobbio. El primero es un legado de carácter metodológico, que consiste en dar prioridad a la demostratio por encima de cualquier forma de interpretatio. El segundo es el individualismo, cuyas diferentes declinaciones son decisivas para fundar, medir y valorar las diversas fórmulas políticas que el Leviatán, en cuanto esencia del Estado moderno, puede albergar. El trabajo se cierra con un tercer nivel de comparación sobre la fortuna de Hobbes y de Bobbio entre sus contemporáneos y en nuestros días.

  11. Religión y poder en Hobbes y Marsilio de Padua: similitudes y diferencias

    Directory of Open Access Journals (Sweden)

    Bernardo Bayona Aznar

    2014-11-01

    Full Text Available Marsilio de Padua desarrolló una teoría política muy diferente del pensamiento medieval tradicional e hizo un esfuerzo sin precedentes por dar fundamento racional al poder. Muchas ideas de la Reforma Anglicana están tomadas del Defensor pacis de Marsilio, una obra que a menudo ha sido interpretada como una original anticipación de la teoría moderna del Estado. El artículo presenta una investigación sobre las estrechas semejanzas entre Marsilio y Hobbes acerca del papel de la religión y del poder pontificio. Los dos autores se vieron marcados por la guerra civil, cuya causa atribuían al poder temporal del Papa y del clero. De ahí que defendieran suprimir todo poder de la Iglesia Católica en este mundo, a fin de evitar la coexistencia de gobiernos y jurisdicciones compitiendo entre sí, como una condición para el mantenimiento de la paz. Pero, aunque el número de argumentos parecidos en las teorías de Marsilio y de Hobbes indica gran continuidad entre sus discursos políticos, este ensayo analiza también las notables diferencias que hay entre sus respectivos pensamientos, construidos en épocas diferentes y con elementos filosóficos muy diversos.

  12. Sacralidade e crueldade no direito natural segundo Hobbes e Agamben = Sacredness and cruelty in natural right according to Hobbes and Agamben

    Directory of Open Access Journals (Sweden)

    Costa, Gilcilene Dias da

    2011-01-01

    Full Text Available O presente texto visa discutir o sentido da sacralidade e da crueldade no direito natural e na cena política a partir de Hobbes e Agamben. Relaciona o conceito hobbesiano de estado de natureza às figuras do direito romano arcaico, homo lupus (homem lobo e homo sacer (homem sagrado em seu duplo processo de inclusão/exclusão da vida nua (zoé na vida política (bíos. Adentra nos limites da natureza e da condição humana, a fim de perceber as flutuações de sentido implicadas na situação de abandono que acerca um malfeitor ou bando junto à comunidade, com sua exposição à morte ou desaparecimento social sem as formas sancionadas pela lei. Reitera a permanente fronteira entre animal e humano, limite paradoxal e intransponível, situado entre polidez e nudez, crueldade e sacralidade, bem e mal

  13. Health-related quality of life and unmet healthcare needs in Huntington's disease.

    Science.gov (United States)

    van Walsem, Marleen R; Howe, Emilie I; Ruud, Gunvor A; Frich, Jan C; Andelic, Nada

    2017-01-07

    Huntington's disease (HD) is a rare neurodegenerative disorder with a prevalence of 6 per 100.000. Despite increasing research activity on HD, evidence on healthcare utilization, patients' needs for healthcare services and Health-Related Quality of Life (HRQoL) is still sparse. The present study describes HRQoL in a Norwegian cohort of HD patients, and assesses associations between unmet healthcare and social support service needs and HRQoL. In this cross-sectional population-based study, 84 patients with a clinical diagnosis of HD living in the South-East of Norway completed the HRQoL questionnaire EuroQol, EQ-5D-3L. Unmet needs for healthcare and social support services were assessed by the Needs and Provision Complexity Scale (NPCS). Furthermore, functional ability was determined using the Unified Huntington's Disease Rating Scale (UHDRS) Functional assessment scales. Socio-demographics (age, gender, marital status, occupation, residence, housing situation) and clinical characteristics (disease duration, total functional capacity, comorbidity) were also recorded. Descriptive statistics were used to describe the patients' HRQoL. Regression analyses were conducted in order to investigate the relationship between unmet healthcare needs and self-reported HRQoL. The patients were divided across five disease stages as follows: Stage I: n = 12 (14%), Stage II: n = 22 (27%), Stage III: n = 19 (23%), Stage IV: n = 14 (16%), and Stage V: n = 17 (20%). Overall HRQoL was lowest in patients with advanced disease (Stages IV and V), while patients in the middle phase (Stage III) showed the most varied health profile for the five EQ-5D-3L dimensions. The regression model including level of unmet needs, clinical characteristics and demographics (age and education) accounted for 42% of variance in HRQoL. A higher level of unmet needs was associated with lower HRQoL (β value - 0.228; p = 0.018) whereas a better total functional capacity corresponded to

  14. The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

    Science.gov (United States)

    Begeti, Faye; Tan, Adrian Y K; Cummins, Gemma A; Collins, Lucy M; Guzman, Natalie Valle; Mason, Sarah L; Barker, Roger A

    2013-11-01

    Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

  15. Xeroderma pigmentosum is a definite cause of Huntington's disease-like syndrome.

    Science.gov (United States)

    Garcia-Moreno, Hector; Fassihi, Hiva; Sarkany, Robert P E; Phukan, Julie; Warner, Thomas; Lehmann, Alan R; Giunti, Paola

    2018-01-01

    Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and neurological features. Although it is typical of childhood, late presentations can mimic different neurodegenerative conditions. We report two families presenting as Huntington's disease-like syndromes. The first case (group G) presented with neuropsychiatric features, cognitive decline and chorea. Typical lentigines were only noticed after the neurological disease started. The second case (group B) presented adult-onset chorea and neuropsychiatric symptoms after an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a Huntington's Disease-like syndrome. Classic dermatological and oncological features have to be investigated in choreic patients with negative genetic tests for Huntington's disease-like phenotypes.

  16. Music therapy in Huntington's disease

    NARCIS (Netherlands)

    Bruggen-Rufi, van C.H.M.

    2018-01-01

    The thesis reports about the effects of music therapy with patients in the late stage of Huntington's disease. A literature review, a focus group study, a randomized controlled trial, an evaluation for complex interventions and a case report study are integrated in the thesis. The beneficial

  17. The Wilson films--Huntington's chorea.

    Science.gov (United States)

    Klein, Christine

    2011-12-01

    Wilson's Queen Square Case 9 with Huntington's chorea shows a 68-year-old man with mild to moderate generalized chorea, impaired fixation, and probable cognitive decline in keeping with a diagnosis of Huntington's disease (HD). An age of onset in the late sixties and a negative family history suggest a relatively small expanded trinucleotide repeat in the HTT gene in the patient and reduced penetrance of an even shorter repeat allele in one of his parents. A highly sensitive and specific gene test has been offered worldwide for diagnostic testing of HD for almost two decades. This test, obviously unavailable at Wilson's times, became the historic frontrunner for guidelines of symptomatic, presymptomatic, and prenatal testing for an adult-onset neurodegenerative disorder. Regarding treatment of HD, however, we are still awaiting the successful translation of research results into the development of effective cause-directed, neuropreventive and neurorestaurative therapies. Copyright © 2011 Movement Disorder Society.

  18. The use of olanzapine in Huntington disease accompanied by psychotic symptoms

    Directory of Open Access Journals (Sweden)

    Cafer Alhan

    2014-06-01

    Full Text Available Huntington's disease is an autosomal dominant neurodegenerative disease. The disease begins between the ages of 30-50, including motor symptoms, psychiatric symptoms and is characterized by progressive dementia. Common psychiatric disorders of Huntington’s disease include mood and anxiety disorders, behavior and personality changes. Psychosis is relatively rare. Here, a patient is present, who has Huntington’s disease, which is associated with psychotic symptoms. 61-year-old male patient who were followed for Huntington disease for 25 years was admitted for complaints of thinking of poisoning and refuse to eat something. Patient was started on olanzapine at dose of 5 mg/day. In follow up psychotic symptoms disappeared. Emerging psychotic symptoms in Huntington disease is created a need for antipsychotic treatment. Atypical antipsychotic agents should be preferred in the treatment and as in the case olanzapine may be used as a treatment option should be kept in mind to control both involuntary movements and psychotic symptoms in Huntington's disease with psychotic features. J Clin Exp Invest 2014; 5 (2: 326-328

  19. Willie Hobbs Moore (1934-1994): The First Female African American Physicist

    Science.gov (United States)

    Mickens, Ronald

    2011-03-01

    We discuss the life and career of Willie Hobbs Moore, the first African American woman to receive a doctorate degree in physics. This achievement occurred in June 1972 at the University of Michigan, Ann Arbor, MI. Her dissertation, directed by the renowned spectroscopist Samuel Krimm, was on the subject of ``A Vibrational Analysis of Secondary Chlorides," and focused on a theoretical analysis of the secondary chlorides for polyvinal-chlorine polymers. From 1972--1977, she, Krimm, and collaborators published more than thirty papers on this and related research issues. In addition to an overview of her family background, her careers as a research physicist and scientist working in various industrial laboratories, we discuss the obstacles and successes she encountered at various stages of her life.

  20. Kas Huntington oli prohvet? / Priit Simson

    Index Scriptorium Estoniae

    Simson Priit, 1977-

    2008-01-01

    Autor käsitleb Samuel Huntingtoni teese ning leiab, et tegelikult Huntington ei pakkunud õigustust islamiriikide ründamisele, vaid pigem hoiatas tsivilisatsioonide siseasjusse sekkumise, tekkida võiva ahelreaktsiooni eest, kus üks tsivilisatsiooni liige tõmbab sõtta ka teise

  1. The emotional experiences of family carers in Huntington disease.

    Science.gov (United States)

    Williams, Janet K; Skirton, Heather; Paulsen, Jane S; Tripp-Reimer, Toni; Jarmon, Lori; McGonigal Kenney, Meghan; Birrer, Emily; Hennig, Bonnie L; Honeyford, Joann

    2009-04-01

    This paper is a report of a study conducted to examine the emotional experience of caregiving by family carers of people with Huntington disease and to describe strategies they used to deal with that experience. Huntington disease, commonly diagnosed in young to middle adulthood, is an inherited single gene disorder involving loss of cognitive, motor and neuropsychiatric function. Many family members become caregivers as well as continuing as parents and wage earners. The emotional aspects of caregiving contribute to mental health risks for family members. Focus groups were conducted with 42 adult carers of people with Huntington disease in four United States and two Canadian Huntington disease centers between 2001 and 2005. Data were analyzed through descriptive coding and thematic analysis. All participants reported multiple aspects of emotional distress. Being a carer was described as experiencing disintegration of one's life. Carers attempted to cope by seeking comfort from selected family members, anticipating the time when the care recipient had died and/or using prescription medications. Spousal carers were distressed by the loss of their relationship with their spouse and dealt with this by no longer regarding the person as an intimate partner. Carers were concerned about the disease risk for children in their families and hoped for a cure. Emotional distress can compromise the well-being of family carers, who attempt to maintain multiple roles. Nurses should monitor carer mental health, identify sources of emotional distress and support effective strategies used by carers to mediate distress.

  2. Américo Negrette and Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Moscovich

    2011-08-01

    Full Text Available The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.

  3. Clinical and genetic study of a juvenile-onset Huntington disease

    Directory of Open Access Journals (Sweden)

    HAO Ying

    2012-06-01

    Full Text Available Background Huntington's disease (HD is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (IT15 locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG in the first exon. The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile-onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile-onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of IT15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile-onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of IT15. His father carried 17/37 and mother carried 15/17. Conclusion 1 The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2 The dynamic mutation of IT15 gene expansion of the CAG repeats in the

  4. A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Eirini Kalliolia

    Full Text Available Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting, 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington's disease group and controls. Daytime growth hormone secretion was similar in control and Huntington's disease subjects. Stage II/III Huntington's disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington's disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.The relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many

  5. The role of tau in the pathological process and clinical expression of Huntington's disease

    DEFF Research Database (Denmark)

    Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan

    2015-01-01

    and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated......-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report...... not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some...

  6. Materialismo percettivo. Da Democrito a Lenin, da Hobbes a Kim

    Directory of Open Access Journals (Sweden)

    Michele Gardini

    2012-05-01

    Full Text Available The paper tries to outline something like a short “critique of pure materialism” in the domain of perception, a sketch showing – through a series of examples, picked out in an apparently heterogeneous fashion from the Western philosophical tradition – how this epistemological model each time, and in everyone of its forms, fails in giving account of the basic features of perceiving.  After giving a survey of authors like Democritus, Hobbes, De Sade, Lenin, the final appendix, devoted to the concept of “supervenience” and its treatment in Davidson and Kim, aims at summarizing the whole problem through the categories of the contemporary philosophy of mind. The conclusion is that a pure materialistic approach is incapable to give reason to some of the fundamental characteristics of perception, that make it one of the basic moods of “being-in-the-world”.

  7. Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.

    Science.gov (United States)

    van Duijn, Erik; Vrijmoeth, Eslie M; Giltay, Erik J; Bernhard Landwehrmeyer, G

    2018-03-01

    Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior. We included 1451 HD gene expansion carriers (age 48.4 years (SD 14.0), 54.8% female) of the REGISTRY study of the European Huntington's Disease Network. Lifetime suicidal ideation and suicidal behavior were assessed with the Columbia-Suicidal Severity Rating Scale. Motor symptoms and disease stage were assessed using subscales of the Unified Huntington's Disease Rating Scale, and depressed mood and irritability were assessed by the Problem Behaviors Assessment. Lifetime passive suicidal ideation was reported by 21.2%. Participants in stage II showed the highest prevalence rate of suicidal ideation, while participants in stage IV/V showed the highest prevalence of suicidal behavior. A lifetime suicide attempt was reported by 6.5% of the HD gene expansion carriers. In multivariate regression analyses, both suicidal ideation and suicidal behavior were associated with a depressed mood, and to a lesser extend to irritability. Results may have been affected by denial or recall bias and no conclusions can be made about the temporal and causal relationships with depressed mood and irritability because of the cross-sectional analyses. Given the high prevalence of suicidal ideation and suicidal behavior in all stages of HD, it is important to screen HD gene expansion carriers for suicidal ideation and suicidal behavior on a regular basis in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere

    International Nuclear Information System (INIS)

    Doggett, N.A.; Cheng, J.F.; Smith, C.L.; Cantor, C.R.

    1989-01-01

    The genetic defect responsible for Huntington disease was originally localized near the tip of the short arm of chromosome 4 by genetic linkage to the locus D4S10. Several markers closer to Huntington disease have since been isolated, but these all appear to be proximal to the defect. A physical map that extends from the most distal of these loci, D4S90, to the telomere of chromosome 4 was constructed. This map identifies at least two CpG islands as markers for Huntington disease candidate genes and places the most likely location of the Huntington disease defect remarkably close (within 325 kilobases) to the telomere

  9. [The life as a caregiver of a person affected by Chorea Huntington: multiple case study].

    Science.gov (United States)

    Winkler, Evi; Ausserhofer, Dietmar; Mantovan, Franco

    2012-10-01

    Chorea Huntington is an autosomal dominantly inherited, neurodegenerative brain disorder that leads to involuntary hyperkinesia, psychotic symptoms and dementia. The illness not only changes the life of the person itself but also the world of the caregivers. The challenges in the care of a person which is affected by Chorea Huntington have an effect on the daily living as an assemblage of natural and social conditions. a multiple case study was conducted. It included semi-structured interviews with three caregivers of people with Chorea Huntington in South Tyrol. The qualitative data was analyzed using the qualitative structured analysis of Mayring (2007). The objective of this study was to describe the phenomenon of change of life from family members that care people affected by Chorea Huntington in a specific cultural setting (South Tyrol, Italy). The caregivers reported that the diagnosis of Chorea Huntington leads to negative changes in "relationship and family". Particularly, frustration, aggression, impatience and apathy were perceived as stressful. At the same time they highlight the positive changes through home care. They report that the relationship became more intimate and integral and it was characterized by more cohesion. Family caregivers get valuable support from the home care service, however, they complain that there is no facility in South Tyrol, which is specialized to care people with Chorea Huntington. Therefore, the caregivers have to "give up a lot" and don't have any personal desires, dreams and expectations for the future. The caregivers have learned independently to deal with their changed life step by step, and to see also the positive effects of the caring role. The life of family caregivers of a person which is affected by Chorea Huntington is characterized by abandonment. A continuous and professional care would be important for the affected and his caregiver. A continuous and professional care is important for both, addressing the

  10. An image-based model of brain volume biomarker changes in Huntington's disease.

    Science.gov (United States)

    Wijeratne, Peter A; Young, Alexandra L; Oxtoby, Neil P; Marinescu, Razvan V; Firth, Nicholas C; Johnson, Eileanoir B; Mohan, Amrita; Sampaio, Cristina; Scahill, Rachael I; Tabrizi, Sarah J; Alexander, Daniel C

    2018-05-01

    Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from premanifest through to manifest stages. We employ a probabilistic event-based model to determine the sequence of appearance of atrophy in brain volumes, learned from structural MRI in the Track-HD study, as well as to estimate the uncertainty in the ordering. We use longitudinal and phenotypic data to demonstrate the utility of the patient staging system that the resulting model provides. The model recovers the following order of detectable changes in brain region volumes: putamen, caudate, pallidum, insula white matter, nonventricular cerebrospinal fluid, amygdala, optic chiasm, third ventricle, posterior insula, and basal forebrain. This ordering is mostly preserved even under cross-validation of the uncertainty in the event sequence. Longitudinal analysis performed using 6 years of follow-up data from baseline confirms efficacy of the model, as subjects consistently move to later stages with time, and significant correlations are observed between the estimated stages and nonimaging phenotypic markers. We used a data-driven method to provide new insight into Huntington's disease progression as well as new power to stage and predict conversion. Our results highlight the potential of disease progression models, such as the event-based model, to provide new insight into Huntington's disease progression and to support fine-grained patient stratification for future precision medicine in Huntington's disease.

  11. Destination and source memory in Huntington's disease

    NARCIS (Netherlands)

    El Haj, M.; Caillaud, M.; Verny, C.; Fasotti, L.; Allain, P.

    2016-01-01

    Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults

  12. Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey.

    Science.gov (United States)

    Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R

    2009-06-09

    To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. Cross sectional, self reported survey. Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (PGenetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.

  13. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth

    2013-01-01

    BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepir......BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect...... of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington...... between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL...

  14. An improved assay for the determination of Huntington`s disease allele size

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

    1994-09-01

    The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

  15. Music therapy in Huntington's disease: a protocol for a multi-center randomized controlled trial.

    Science.gov (United States)

    van Bruggen-Rufi, Monique; Vink, Annemieke; Achterberg, Wilco; Roos, Raymund

    2016-07-26

    Huntington's disease is a progressive, neurodegenerative disease with autosomal dominant inheritance, characterized by motor disturbances, cognitive decline and behavioral and psychological symptoms. Since there is no cure, all treatment is aimed at improving quality of life. Music therapy is a non-pharmacological intervention, aiming to improve the quality of life, but its use and efficacy in patients with Huntington's disease has hardly been studied. In this article, a protocol is described to study the effects of music therapy in comparison with a control intervention to improve quality of life through stimulating expressive and communicative skills. By targeting these skills we assume that the social-cognitive functioning will improve, leading to a reduction in behavioral problems, resulting in an overall improvement of the quality of life in patients with Huntington's disease. The study is designed as a multi-center single-blind randomised controlled intervention trial. Sixty patients will be randomised using centre-stratified block-permuted randomisation. Patients will be recruited from four long-term care facilities specialized in Huntington's disease-care in The Netherlands. The outcome measure to assess changes in expressive and communication skills is the Behaviour Observation Scale Huntington and changes in behavior will be assessed by the Problem Behaviour Assesment-short version and by the BOSH. Measurements take place at baseline, then 8, 16 (end of intervention) and 12 weeks after the last intervention (follow-up). This randomized controlled study will provide greater insight into the effectiveness of music therapy on activities of daily living, social-cognitive functioning and behavior problems by improving expressive and communication skills, thus leading to a better quality of life for patients with Huntington's disease. Netherlands Trial Register: NTR4904 , registration date Nov. 15, 2014.

  16. Caregiver roles in families affected by Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2013-01-01

    AIM: The objective of this study was to explore family caregivers' experiences with the impact of Huntington's disease (HD) on the family structure and roles in the family. METHODOLOGY: We interviewed 15 family caregivers in families affected by HD, based on a semi-structured interview guide...... for impairments by taking on adult responsibilities, and in some families, a child had the role as main caregiver. The increasing need for care could cause conflicts between the role as family member and family caregiver. The burden of care within the family could fragment and isolate the family. CONCLUSIONS......: Huntington's disease has a major impact on family systems. Caregiver roles are shaped by impairments in the affected family member and corresponding dynamic adoption and change in roles within the family. Making assessments of the family structure and roles, professionals may understand more about how...

  17. 77 FR 71636 - Huntington Foam LLC, Fort Smith, AR; Notice of Revised Determination on Reconsideration

    Science.gov (United States)

    2012-12-03

    ... Smith, AR; Notice of Revised Determination on Reconsideration On August 8, 2012, the Department of Labor... workers and former workers of Huntington Foam LLC, Fort Smith, Arkansas (subject firm). The workers are... reconsideration investigation, I determine that workers of Huntington Foam LLC, Fort Smith, Arkansas, who were...

  18. Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease

    DEFF Research Database (Denmark)

    Khakh, Baljit S.; Beaumont, Vahri; Cachope, Roger

    2017-01-01

    Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter...

  19. [Sporadic juvenile forms of Huntington's chorea].

    Science.gov (United States)

    Zinchenko, A P; Goncharov, V D; Burtianskii, D L; Zakhar'ev, Iu M

    1980-01-01

    Six patients with Huntington's chorea in the age of 15-24 years old, suffered from diffusive choreic hyperkynesis with slowly progressive dementia. The development of this disease in childhood and adolescence was atypical, as nobody in the family and in kin sufferred from it and it was difficult to diagnose the disease. Recognition of the disease was promoted by pneumoencephalography, electromyography and memory investigation.

  20. Did the "Woman in the Attic" in Jane Eyre Have Huntington Disease?

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Coon

    2015-07-01

    Full Text Available Background: References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Aim: Our aim was to compare Charlotte Brontë’s depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington’s original essay “On chorea” with the hypothesis that Mason was displaying features of Huntington disease. Results: Charlotte Brontë’s 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington’s tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Conclusion: Brontë’s character had features of Huntington disease as originally described by Huntington. Brontë’s keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era.

  1. Motor cortex synchronization influences the rhythm of motor performance in premanifest huntington's disease.

    Science.gov (United States)

    Casula, Elias P; Mayer, Isabella M S; Desikan, Mahalekshmi; Tabrizi, Sarah J; Rothwell, John C; Orth, Michael

    2018-03-01

    In Huntington's disease there is evidence of structural damage in the motor system, but it is still unclear how to link this to the behavioral disorder of movement. One feature of choreic movement is variable timing and coordination between sequences of actions. We postulate this results from desynchronization of neural activity in cortical motor areas. The objective of this study was to explore the ability to synchronize activity in a motor network using transcranial magnetic stimulation and to relate this to timing of motor performance. We examined synchronization in oscillatory activity of cortical motor areas in response to an external input produced by a pulse of transcranial magnetic stimulation. We combined this with EEG to compare the response of 16 presymptomatic Huntington's disease participants with 16 age-matched healthy volunteers to test whether the strength of synchronization relates to the variability of motor performance at the following 2 tasks: a grip force task and a speeded-tapping task. Phase synchronization in response to M1 stimulation was lower in Huntington's disease than healthy volunteers (P synchronization (r = -0.356; P synchronization and desynchronization could be a physiological basis for some key clinical features of Huntington's disease. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  2. Potência de ação e ordem: o poder e a razão segundo Nicolau Maquiavel e Thomas Hobbes

    OpenAIRE

    Kersting, Wolfgang

    2006-01-01

    O autor apresenta aborda, primeiramente, a relação entre poder e razão no pensamento político de Maquiavel. Num segundo momento, apresenta, no pensamento de Hobbes, a trajetória que se estende da razão impotente do estado de natureza até à razão poderosa do Estado, dispensador de segurança

  3. Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

    Science.gov (United States)

    Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

    2015-08-01

    Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease

  4. Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

    Science.gov (United States)

    Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

    1980-12-01

    Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

  5. The Hobbs Oil and Water Experimental Facility of the Waste-Management Education and Research Consortium

    International Nuclear Information System (INIS)

    Martin, F.D.; Bretz, R.E.; Bowman, R.S.; Kieft, T.L.; Cadena, F.

    1992-01-01

    The Hobbs Oil and Water Experimental (HOWE) Facility came on-line as a research component of the Waste-Management Education and Research Consortium (WERC) when funding for the Consortium became official in late February 1990. As a support facility for WERC, which was established to expand the ability of this nation to manage hazardous, radioactive, and solid wastes through a multidisciplinary approach, HOWE can tap into the expertise that resides at three major New Mexico universities, on Native American community college, and two national laboratories. The intention of the HOWE is to provide education, as well as research and development programs, that reflect concerns of the petroleum industry in the United States. Personnel work to solve environmental problems and assess the impact to the industry of regulatory actions pertaining to those problems. Leadership for the program is provided from the New Mexico Institute of Mining and Technology at Socorro, NM, by Technical Leaders F.D. Martin, Director of the Petroleum Recovery Research Center, and Dr. R.E. Bretz of the petroleum engineering faculty. The HOWE site is administered by Mike DeMarco, Director of the Petroleum Technology Program at the New Mexico Junior College in Hobbs, NM. Currently, the HOWE laboratory is being provided with state-of-the-art equipment to support research projects or field demonstration activities. Programs include research pertaining to groundwater pollution transport processes, slurry-phase bioremediation of oilfield production pit sludges, and treatment of produced brines or contaminated waters. This paper introduces the HOWE and discusses the research programs relevant to the petroleum industry that are presently underway or planned. Future collaborative efforts with industry that are presently underway or planned. Future collaborative efforts with industry groups are being encouraged

  6. Beautiful Science: The Public and Private History of Astronomy at the Huntington Library

    Science.gov (United States)

    Lewis, Daniel

    2009-05-01

    The history of astronomy has a long tradition within research libraries. The rare collections at the Huntington Library (encompassing American and British history from around 1000 CE to the present, in many different subject areas) are among the most heavily-used in the United States, The history of astronomy holdings are a cornerstone within the library's history of science holdings. This talk will present the two faces of the history of astronomy holdings at the Huntington Library. The first of these is the research end of operations: what the collections consist of, how the scholarly public uses the collections, and what the implications are for modern astronomical practice. The second element concerns the public exhibit face of the history of astronomy holdings at The Huntington. Of the 600,000 people who visit the Huntington each year, the majority visit public displays and rare book and manuscript exhibits. "Beautiful Science: Ideas That Changed the World” is a new permanent history of science exhibit. One quarter of the exhibit relates to the history of astronomy. Public exhibits require a particular kind of planning and bring a specific set of values to the history of astronomy. Public exhibits also have their own concerns, and this talk will cover a number of those issues as well as the research issues.

  7. Potência de ação e ordem: o poder e a razão segundo Nicolau Maquiavel e Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Kersting, Wolfgang

    2006-01-01

    Full Text Available O autor apresenta aborda, primeiramente, a relação entre poder e razão no pensamento político de Maquiavel. Num segundo momento, apresenta, no pensamento de Hobbes, a trajetória que se estende da razão impotente do estado de natureza até à razão poderosa do Estado, dispensador de segurança

  8. JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

    Science.gov (United States)

    Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

    2015-01-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  9. Clinical neurogenetics: huntington disease.

    Science.gov (United States)

    Bordelon, Yvette M

    2013-11-01

    Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington's disease

    DEFF Research Database (Denmark)

    Petersen, Maria Hvidberg; Budtz-Jørgensen, Esben; Sørensen, Sven Asger

    2014-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led to the inve......Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led...

  11. Ethical issues and Huntington's disease | Kromberg | South African ...

    African Journals Online (AJOL)

    The practice of genetic counselling gives rise to many ethical dilemmas, and counsellors need to be familiar with the principles of biomedical ethics. The primary principles include respect for autonomy, beneficence, non-maleficence and justice. A case of identical twins at 50% risk for Huntington's disease, in which only one ...

  12. Le Léviathan dans la doctrine de l’État de Thomas Hobbes : sens et échec du décisionnisme politique

    Directory of Open Access Journals (Sweden)

    Emmanuel Tuchscherer

    2005-06-01

    Full Text Available Présenté en 1938, le Der Leviathan de Carl Schmitt clos un ensemble de réflexions que le juriste et politologue allemand a consacré au décisionnisme politique. Au long de son commentaire sur Hobbes, Schmitt aboutit toutefois à un résultat inattendu. Naguère loué comme « le cas classique de la pensée décisionniste », Hobbes s’est métamorphosé à son insu en « ancêtre spirituel » de l’État législateur et libéral-constitutionnel. Schmitt a trouvé chez son allié le plus précieux les germes d’une pensée qu’il n’a cessé d’éreinter sous toutes ses formes, qu’on la décline dans sa version techniciste, positiviste, constitutionnaliste bourgeoise et libérale, individualiste ou pluraliste. C’est en ce sens que le Der Leviathan résume à bien des égards le sens et l’échec du décisionnisme politique.

  13. Characterisation of aggression in Huntington's disease: rates, types and antecedents in an inpatient rehabilitation setting.

    Science.gov (United States)

    Brown, Anahita; Sewell, Katherine; Fisher, Caroline A

    2017-10-01

    To systematically review aggression in an inpatient Huntington's cohort examining rates, types and antecedents. Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's disease or antecedents that contribute to its occurrence. A systematic, double-coded, electronic medical file audit. The electronic hospital medical records of 10 people with Huntington's disease admitted to a brain disorders unit were audited for a 90-day period using the Overt Aggression Scale-Modified for Neurorehabilitation framework, yielding 900 days of clinical data. Nine of 10 clients exhibited aggression during the audit period. Both verbal (37·1%) aggression and physical aggression were common (33·8%), along with episodes of mixed verbal and physical aggression (15·2%), while aggression to objects/furniture was less prevalent (5·5%). The most common antecedent was physical guidance with personal care, far exceeding any other documented antecedents, and acting as the most common trigger for four of the nine clients who exhibited aggression. For the remaining five clients, there was intraindividual heterogeneity in susceptibility to specific antecedents. In Huntington's sufferers at mid- to late stages following disease onset, particular care should be made with personal care assistance due to the propensity for these procedures to elicit an episode of aggression. However, given the degree of intraindividual heterogeneity in susceptibility to specific antecedents observed in the present study, individualised behaviour support plans and sensory modulation interventions may be the most useful in identifying triggers and managing aggressive episodes. Rates of aggression in Huntington's disease inpatients can be high. Knowledge of potential triggers, such as personal care, is important for nursing and care staff, so that attempts can be

  14. Family caregivers' views on coordination of care in Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2015-01-01

    BACKGROUND: Collaboration between family caregivers and health professionals in specialised hospitals or community-based primary healthcare systems can be challenging. During the course of severe chronic disease, several health professionals might be involved at a given time, and the patient......'s illness may be unpredictable or not well understood by some of those involved in the treatment and care. AIM: The aim of this study was to explore the experiences and expectations of family caregivers for persons with Huntington's disease concerning collaboration with healthcare professionals. METHODS......: To shed light on collaboration from the perspectives of family caregivers, we conducted an explorative, qualitative interview study with 15 adult participants experienced from caring for family members in all stages of Huntington's disease. Data were analysed with systematic text condensation, a cross...

  15. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

  16. Palliative Care in Huntington Disease: Personal Reflections and a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Christopher G. Tarolli

    2017-04-01

    Full Text Available Background Huntington disease is a fatal, autosomal dominant, neurodegenerative disorder manifest by the triad of a movement disorder, behavioral disturbances, and dementia. At present, no curative or disease modifying therapies exist for the condition and current treatments are symptomatic. Palliative care is an approach to care that focuses on symptom relief, patient and caregiver support, and end of life care. There is increasing evidence of the benefit of palliative care throughout the course of neurodegenerative conditions including Parkinson disease and amyotrophic lateral sclerosis. However, beyond its application at the end of life, little is known about the role of palliative care in Huntington disease.Methods In this article, we discuss what is known about palliative care in Huntington disease, specifically related to early disease burden, caregiver burnout, advance care planning, and end of life care.Results We provide a review of the current literature and discuss our own care practices.Discussion We conclude by discussing questions that remain unanswered and positing ideas for future work in the field.

  17. Huntington Revisited: Is Conservative Realism Still Essential for the Military Ethic

    National Research Council Canada - National Science Library

    Mahoney-Norris, Kathleen A

    2001-01-01

    ...). Furthermore, Huntington has developed what appears to be a powerful argument as to why conservative realism should be considered a fundamental component of the professional ethic of the military officer...

  18. The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

    Science.gov (United States)

    Lescaudron, L; Naveilhan, P; Neveu, I

    2012-01-01

    Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

  19. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  20. Hypocretin and melanin-concentrating hormone in patients with Huntington disease.

    NARCIS (Netherlands)

    Aziz, A.; Fronczek, R.; Maat-Schieman, M.L.; Unmehopa, U.A.; Roelandse, F.W.; Overeem, S.; Duinen, S.G. van; Lammers, G.J.; Swaab, D.F.; Roos, R.A.C.

    2008-01-01

    To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin and MCH neurons and estimated their total numbers in the lateral hypothalamus of both HD patients

  1. Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.

    Science.gov (United States)

    Cisbani, Giulia; Maxan, Alexander; Kordower, Jeffrey H; Planel, Emmanuel; Freeman, Thomas B; Cicchetti, Francesca

    2017-11-01

    Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative

  2. Towards a phenomenology of civil war: Hobbes meets Benjamin in Beirut.

    Science.gov (United States)

    De Cauter, Lieven

    2011-01-01

    Based on interviews with Beirut intellectuals and architects, this essay endeavours to trace the contours for a phenomenology or anthropology of civil war. Thomas Hobbes serves as a guide, with his idea of civil war representing a relapse into the ‘state of nature’; as absence of sovereignty resulting in a ‘war of everybody against everybody’. The effects of ever-latent civil war in Beirut are far-reaching: the fragmentation of urban space and the disappearance of public space, the loss of memory and the fragmentation of time, even the reification of language. In the collective imagination and in the arts, Beirut appears as a ghost town, a spectral city with a spectral civility. What we discover is a city, its inhabitants, its social behaviour, but also its art and literature, in the grip of post-traumatic stress syndrome. From all this, we take home two things: first, any city can (at least in principle) relapse into a similar state of nature — Beirut can become a paradigm of latent civil war; and second, the traumatic modernity of Beirut mirrors the traumatic artistic expressions of modernism — the shock of modernity is also always a modernity of shock.

  3. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

    Science.gov (United States)

    2008-12-01

    To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

  4. Remifentanil in a patient with Huntington's chorea - case report ...

    African Journals Online (AJOL)

    Relatively few published case reports related to the anaesthetic management of Huntington's chorea (HC) exist. At the time of surgery no publications were found related to remifentanil's use in patients with HC. This case report describes the management of a confirmed HC patient requiring urgent decompression of a spinal ...

  5. Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease.

    Science.gov (United States)

    Gaura, Véronique; Lavisse, Sonia; Payoux, Pierre; Goldman, Serge; Verny, Christophe; Krystkowiak, Pierre; Damier, Philippe; Supiot, Frédéric; Bachoud-Levi, Anne-Catherine; Remy, Philippe

    2017-09-01

    Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease. To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. This study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity. Statistical parametric mapping software (SPM5) was used to identify all hypo- and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism. Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3

  6. High Protein Diet and Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

  7. Psychodynamic theory and counseling in predictive testing for Huntington's disease.

    Science.gov (United States)

    Tassicker, Roslyn J

    2005-04-01

    This paper revisits psychodynamic theory, which can be applied in predictive testing counseling for Huntington's Disease (HD). Psychodynamic theory has developed from the work of Freud and places importance on early parent-child experiences. The nature of these relationships, or attachments are reflected in adult expectations and relationships. Two significant concepts, identification and fear of abandonment, have been developed and expounded by the psychodynamic theorist, Melanie Klein. The processes of identification and fear of abandonment can become evident in predictive testing counseling and are colored by the client's experience of growing up with a parent affected by Huntington's Disease. In reflecting on family-of-origin experiences, clients can also express implied expectations of the future, and future relationships. Case examples are given to illustrate the dynamic processes of identification and fear of abandonment which may present in the clinical setting. Counselor recognition of these processes can illuminate and inform counseling practice.

  8. A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    John P Miller

    Full Text Available A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity. Ontology analysis of suppressor data identified processes previously implicated in Huntington's disease, including proteolysis, glutamate excitotoxicity, and mitochondrial dysfunction. In addition to established mechanisms, the screen identified multiple components of the RRAS signaling pathway as loss-of-function suppressors of mutant huntingtin toxicity in human and mouse cell models. Loss-of-function in orthologous RRAS pathway members also suppressed motor dysfunction in a Drosophila model of Huntington's disease. Abnormal activation of RRAS and a down-stream effector, RAF1, was observed in cellular models and a mouse model of Huntington's disease. We also observe co-localization of RRAS and mutant huntingtin in cells and in mouse striatum, suggesting that activation of R-Ras may occur through protein interaction. These data indicate that mutant huntingtin exerts a pathogenic effect on this pathway that can be corrected at multiple intervention points including RRAS, FNTA/B, PIN1, and PLK1. Consistent with these results, chemical inhibition of farnesyltransferase can also suppress mutant huntingtin toxicity. These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease.

  9. O leviatã e as guerras religiosas do século XVII: uma analise do estado absolutista a partir de Thomas Hobbes

    OpenAIRE

    Lima, Danilo Pereira; UNISINOS - Universidade do Vale do Rio dos Sinos

    2015-01-01

    Currently recognized as one of the leading theorists of political philosophy of the seventeenth century, Hobbes had his thinking involved in major political and religious wars, which, at that time, threatened to dissolve the nascent British state organization. Thus, this study aims to analyze the major political, social and philosophical events that somehow ended up influencing the Hobbesian thinking about the formation of the absolutist state, since for him, where there were no common power ...

  10. The Effect of Music Therapy in Patients with Huntington's Disease: A Randomized Controlled Trial.

    Science.gov (United States)

    van Bruggen-Rufi, Monique C H; Vink, Annemieke C; Wolterbeek, Ron; Achterberg, Wilco P; Roos, Raymund A C

    2017-01-01

    Music therapy may have beneficial effects on improving communication and expressive skills in patients with Huntington's disease (HD). Most studies are, however, small observational studies and methodologically limited. Therefore we conducted a multi-center randomized controlled trial. To determine the efficacy of music therapy in comparison with recreational therapy in improving quality of life of patients with advanced Huntington's disease by means of improving communication. Sixty-three HD-patients with a Total Functional Capacity (TFC) score of ≤7, admitted to four long-term care facilities in The Netherlands, were randomized to receive either group music therapy or group recreational therapy in 16 weekly sessions. They were assessed at baseline, after 8, 16 and 28 weeks using the Behaviour Observation Scale for Huntington (BOSH) and the Problem Behaviour Assessment-short version (PBA-s). A linear mixed model with repeated measures was used to compare the scores between the two groups. Group music therapy offered once weekly for 16 weeks to patients with Huntington's disease had no additional beneficial effect on communication or behavior compared to group recreational therapy. This was the first study to assess the effect of group music therapy on HD patients in the advanced stages of the disease. The beneficial effects of music therapy, recorded in many, mainly qualitative case reports and studies, could not be confirmed with the design (i.e. group therapy vs individual therapy) and outcome measures that have been used in the present study. A comprehensive process-evaluation alongside the present effect evaluation is therefore performed.

  11. La decisione Holt v. Hobbs: una svolta nelle politiche di religious accommodation con riguardo agli istituti di detenzione nell’ordinamento statunitense?

    Directory of Open Access Journals (Sweden)

    Adelaide Madera

    2016-11-01

    SOMMARIO: 1. La libertà religiosa negli istituti di detenzione negli U.S.A. e il caso Holt v. Hobbs – 2. Le esigenze di bilanciamento fra libertà religiosa ed esigenze di ordine e sicurezza nelle istituzioni penitenziarie – 3. La diluizione delle forme di tutela della libertà religiosa nel contesto degli istituti di detenzione – 4. L’impatto del R.F.R.A. sulla tutela della libertà religiosa negli istituti di detenzione – 5. L’adozione del R.L.U.I.P.A. – 6. Il riconoscimento di legittimità del R.L.U.I.P.A. alla luce dell’Establishment Clause – 7. I nodi irrisolti del caso Cutter v. Wilkinson – 8. Le interferenze del Prison Litigation Reform Actsulla tutela dell’esercizio della libertà religiosa dei detenuti – 9. La frammentazione dei parametri adoperati dai diversi circuiti d’appello – 10. La decisione Holt v. Hobbs – 11. Le motivazioni della Corte – 12. Il (parziale ridimensionamento del parametro della due deference – 13. La tutela estensiva della libertà religiosa promossa dalla Corte Roberts – 14. Holt e Hobby Lobby a confronto – 15. Il crescente rilievo assunto dall’elemento dei third-party burdens nella giurisprudenza della Corte – 16. Annotazioni conclusive.

  12. Functional Compensation of Motor Function in Pre-Symptomatic Huntington's Disease

    Science.gov (United States)

    Kloppel, Stefan; Draganski, Bogdan; Siebner, Hartwig R.; Tabrizi, Sarah J.; Weiller, Cornelius; Frackowiak, Richard S. J.

    2009-01-01

    Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of…

  13. Challenges of Huntington's disease and quest for therapeutic biomarkers

    Czech Academy of Sciences Publication Activity Database

    Kotrčová, Eva; Jarkovská, Karla; Valeková, Ivona; Žižková, Martina; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 9, 1-2 (2015), s. 147-158 ISSN 1862-8346 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : HD biomarkers * Huntington´s disease * Huntingtin neurotoxicity * Huntingtin pathogenesis Subject RIV: FH - Neurology Impact factor: 2.959, year: 2015

  14. Vertraagde diagnose van de ziekte van Huntington in een psychiatrische setting

    NARCIS (Netherlands)

    Tak, L M; Sizoo, B; de Stegge, B M Aan; Adema, S; van Duijn, E; Kremer, B

    2017-01-01

    Huntington's disease (hd) is characterised by a triad of neuropsychiatric symptoms, motor disturbances and cognitive decline. If initial symptoms are of neuropsychiatric nature they maybe misinterpreted, which can lead to delayed diagnosis. Three examples of delayed hd diagnosis in a psychiatric

  15. Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis.

    Science.gov (United States)

    Long, Jeffrey D; Mills, James A; Leavitt, Blair R; Durr, Alexandra; Roos, Raymund A; Stout, Julie C; Reilmann, Ralf; Landwehrmeyer, Bernhard; Gregory, Sarah; Scahill, Rachael I; Langbehn, Douglas R; Tabrizi, Sarah J

    2017-11-01

    Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in HTT gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT). Track had 167 prediagnosis mutation carriers and 156 noncarriers, whereas COHORT had 366 prediagnosis mutation carriers and noncarriers. Track studies were conducted at 4 sites in 4 countries (Canada, France, England, and the Netherlands) from which data were collected from January 17, 2008, through November 17, 2014. The COHORT was conducted at 38 sites in 3 countries (Australia, Canada, and the United States) from which data were collected from February 14, 2006, through December 31, 2009. Results from the Track data were externally validated with data from the COHORT. The required sample size was estimated for a 2-arm prediagnosis clinical trial. Data analysis took place from May 1, 2016, to June 10, 2017. The primary end point is PFS. Huntington disease progression events are defined for the Unified Huntington's Disease Rating Scale total motor score, total functional capacity, symbol digit modalities test, and Stroop word test. Of Track's 167 prediagnosis mutation carriers, 93 (55.6%) were women, and the mean (SD) age was 40.06 (8.92) years; of the 156 noncarriers, 87 (55.7%) were women, and the mean (SD) age was 45.58 (10.30) years. Of the 366 COHORT participants, 229 (62.5%) were women and the mean (SD) age was 42.21 (12.48) years. The PFS curves of the Track mutation carriers showed good external validity with the COHORT mutation carriers after adjusting for initial progression. For

  16. Émile Durkheim a tzv. Hobbesův problém řádu: Co se skrývá na dně 'prvního ze sociologických mýtů'?

    Czech Academy of Sciences Publication Activity Database

    Maršálek, Jan

    2008-01-01

    Roč. 30, 3-4 (2008), s. 161-184 ISSN 1210-0250 Institutional research plan: CEZ:AV0Z9009908 Keywords : Durkheim * Hobbes * Spencer * political philosophy * general sociology * individualism * theory of the state Subject RIV: AA - Philosophy ; Religion

  17. Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

    Science.gov (United States)

    Agosta, Federica; Altomare, Daniele; Festari, Cristina; Orini, Stefania; Gandolfo, Federica; Boccardi, Marina; Arbizu, Javier; Bouwman, Femke; Drzezga, Alexander; Nestor, Peter; Nobili, Flavio; Walker, Zuzana; Pagani, Marco

    2018-05-01

    To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.

  18. First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Jha, Tarun; Gayen, Shovanlal

    2016-12-01

    Huntington's disease (HD) is caused by mutation of huntingtin protein (mHtt) leading to neuronal cell death. The mHtt induced toxicity can be rescued by inhibiting the kynurenine monooxygenase (KMO) enzyme. Therefore, KMO is a promising drug target to address the neurodegenerative disorders such as Huntington's diseases. Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches. Moreover, ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Huntington's Disease in a Patient Misdiagnosed as Conversion Disorder.

    Science.gov (United States)

    Nogueira, João Machado; Franco, Ana Margarida; Mendes, Susana; Valadas, Anabela; Semedo, Cristina; Jesus, Gustavo

    2018-01-01

    Huntington's disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington's disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.

  20. “Manda quem pode, obedece quem tem juízo”: ou sobre a (desobediência e a razão em Hobbes

    Directory of Open Access Journals (Sweden)

    Rita Helena Sousa Ferreira Gomes

    2011-11-01

    Full Text Available Partindo do dito popular “manda quem pode, obedece quem tem juízo” o presente artigo tem como objetivo defender a tese de que o Estado hobbesiano sustenta-se tanto pela força quanto pela razáo. Dentro desta perspectiva, será analisada a noçáo de desobediência e, ao final, mostrar-se-á que o adágio referido só pode ser tido como verdadeiro de acordo com a filosofia política de Thomas Hobbes após feitas certas ressalvas.

  1. Personality Traits in Huntington's Disease

    DEFF Research Database (Denmark)

    Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua

    2016-01-01

    Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene......-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons...... symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms....

  2. Current status of PET imaging in Huntington's disease

    International Nuclear Information System (INIS)

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-01-01

    To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading ''Huntington Disease'' combined with text and key words ''Huntington Disease'', ''Neuroimaging'' and ''PET''. Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([ 18 F]FDG and [ 15 O]H 2 O), presynaptic ([ 18 F]fluorodopa, [ 11 C]β-CIT and [ 11 C]DTBZ) and postsynaptic ([ 11 C]SCH22390, [ 11 C]FLB457 and [ 11 C]raclopride) dopaminergic function, phosphodiesterases ([ 18 F]JNJ42259152, [ 18 F]MNI-659 and [ 11 C]IMA107), and adenosine ([ 18 F]CPFPX), cannabinoid ([ 18 F]MK-9470), opioid ([ 11 C]diprenorphine) and GABA ([ 11 C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment

  3. 3-NP-induced neurodegeneration studies in experimental models of Huntington's disease.

    NARCIS (Netherlands)

    Vis, J.C.

    2005-01-01

    This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this

  4. Huntington's disease does not appear to increase the risk of diabetes mellitus

    DEFF Research Database (Denmark)

    Boesgaard, T W; Nielsen, Troels Tolstrup; Josefsen, Knud Elnegaard

    2009-01-01

    Huntington's disease (HD) is an autosomal, dominantly inherited, neurodegenerative disorder characterised by neurological, cognitive and psychiatric symptoms. HD has been associated with diabetes mellitus, which is, to some extent, supported by studies in transgenic HD mice. In transgenic mice...

  5. SOBRE O ESTADO DE NATUREZA E O ESTADO CIVIL: UM DIÁLOGO ENTRE THOMAS HOBBES E IMMANUEL KANT

    Directory of Open Access Journals (Sweden)

    Andreza Barreto Leitão

    2010-08-01

    Full Text Available No presente trabalho, busca-se trazer à luz as relações entre Estado, Sociedade Civil e garantias de liberdade tendo em vista a evolução do pensamento político a esse respeito. Para tanto, tomou-se como parâmetro a passagem do estado de natureza ao estado civil segundo as concepções de Thomas Hobbes e de Immanuel Kant, levando-se em consideração as influências e os respectivos contextos históricos em que os arcabouços teóricos de cada autor foram erigidos. O primeiro deles veria tal passagem como fruto de um cálculo interessado, o segundo, como resultado de um dever-ser.

  6. 77 FR 22616 - Huntington Asset Advisors, Inc., et al.; Notice of Application

    Science.gov (United States)

    2012-04-16

    ...''), Huntington Strategy Shares (``Trust''), and SEI Investments Distribution Co. Summary of Application.... \\14\\ If Shares are listed on The NASDAQ Stock Market LLC (``Nasdaq'') or a similar electronic Listing... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30032; 812-13785...

  7. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

    2016-01-01

    Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32...

  8. Motor outcome measures in Huntington disease clinical trials.

    Science.gov (United States)

    Reilmann, Ralf; Schubert, Robin

    2017-01-01

    Deficits in motor function are a hallmark of Huntington disease (HD). The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) is a categoric clinical rating scale assessing multiple domains of motor disability in HD. The UHDRS-TMS or subsets of its items have served as primary or secondary endpoints in numerous clinical trials. In spite of a well-established video-based annual online certification system, intra- and interrater variability, subjective error, and rater-induced placebo effects remain a concern. In addition, the UHDRS-TMS was designed to primarily assess motor symptoms in manifest HD. Recently, advancement of technology resulted in the introduction of the objective Q-Motor (i.e., Quantitative-Motor) assessments in biomarker studies and clinical trials in HD. Q-Motor measures detected motor signs in blinded cross-sectional and longitudinal analyses of manifest, prodromal, and premanifest HD cohorts up to two decades before clinical diagnosis. In a multicenter clinical trial in HD, Q-Motor measures were more sensitive than the UHDRS-TMS and exhibited no placebo effects. Thus, Q-Motor measures are currently explored in several multicenter trials targeting both symptomatic and disease-modifying mechanisms. They may supplement the UHDRS-TMS, increase the sensitivity and reliability in proof-of-concept studies, and open the door for phenotype assessments in clinical trials in prodromal and premanifest HD. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Poderes invisíveis versus poderes visíveis no Leviatã de Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Pedro Hermílio Villas Bôas Castelo Branco

    2004-11-01

    Full Text Available O conceito de secularização adotado pelas teorias do Estado moderno permitiu institucionalizar um Estado laico que alterou a concepção de legitimidade, solapando qualquer possibilidade de reivindicação do poder divino pelos governantes. Hoje, porém, depois do 11 de setembro de 2001, acentuou-se a necessidade de repensar o conceito de secularização, precisamente, à luz do papel que a religião desempenha na política interna e externa dos estados. Este artigo sugere que o conceito de secularização nem sempre foi pensado como separação entre o poder espiritual e o poder temporal. A investigação do Leviatã de Thomas Hobbes, obra apontada por muitos como precursora da teoria do Estado moderno, indica outro sentido para a compreensão do conceito de seculariação.

  10. Huntington's disease: a clinical review

    Directory of Open Access Journals (Sweden)

    Roos Raymund AC

    2010-12-01

    Full Text Available Abstract Huntington disease (HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD. The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which

  11. Huntington disease: Experimental models and therapeutic perspectives

    International Nuclear Information System (INIS)

    Serrano Sanchez, Teresa; Blanco Lezcano, Lisette; Garcia Minet, Rocio; Alberti Amador, Esteban; Diaz Armesto, Ivan and others

    2011-01-01

    Huntington's disease (HD) is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment to the disease which having lapsed 15 or 20 years advances inexorably, in a slow form, toward the total inability or death. This paper reviews the clinical and morphological characteristics of Huntington's disease as well as the experimental models more commonly used to study this disease, having as source the articles indexed in Medline data base, published in the last 20 years. Advantages and disadvantages of all experimental models to reproduce the disease as well as the perspectives to therapeutic assay have been also considered. the consent of outline reported about the toxic models, those induced by neurotoxins such as quinolinic acid, appears to be the most appropriate to reproduce the neuropathologic characteristic of the disease, an genetic models contributing with more evidence to the knowledge of the disease etiology. Numerous treatments ameliorate clinical manifestations, but none of them has been able to stop or diminish the affectations derived from neuronal loss. At present time it is possible to reproduce, at least partially, the characteristics of the disease in experimentation animals that allow therapy evaluation in HD. from the treatment view point, the more promissory seems to be transplantation of no neuronal cells, taking into account ethical issues and factibility. On the other hand the new technology of interference RNA emerges as a potential therapeutic tool for treatment in HD, and to respond basic questions on the development of the disease.

  12. High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal

    Directory of Open Access Journals (Sweden)

    Kilbride Seán M

    2011-07-01

    Full Text Available Abstract Background The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2 and complex IV (cytochrome c oxidase EC 1.9.3.1 are reduced by 30-70% in Huntington's disease and Alzheimer's disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal. Results Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-independent glutamate release to occur from isolated nerve terminals (synaptosomes depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca2+-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased. Conclusions These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.

  13. Apolipoprotein E and presenilin-1 genotypes in Huntington's disease.

    Science.gov (United States)

    Panas, M; Avramopoulos, D; Karadima, G; Petersen, M B; Vassilopoulos, D

    1999-07-01

    Huntington's disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer's disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20-65) we determined number of CAG repeats and the distribution of the APOE alleles (epsilon2, epsilon3, epsilon4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the epsilon4 allele (51.6 vs. 38.0 P<0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the epsilon3/epsilon3 genotype while it was not detected in patients with epsilon3/epsilon4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington's disease.

  14. Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

    2005-01-01

    Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

  15. Hobbes en Sinaloa, o del corrido como resolución poética a un orden social marcado por la violencia

    Directory of Open Access Journals (Sweden)

    María Luisa De la Garza Chávez

    2008-06-01

    Full Text Available Este artículo muestra cómo una veta de la producción actual de corridos constituye una forma tan innovadora como radical de actuar frente a una realidad social que tiene mucho en común con el «estado de naturaleza» que Hobbes imaginó como causante del primer pacto político de la historia de la humanidad. En el México de hoy, en el que no se observa otra cosa que el fracaso de la política, la única opción para garantizar la conservación de sí parece radicar en la poética.

  16. Leerse a sí mismo: hermenéutica, política y retórica en Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    María José Rossi

    2014-11-01

    Full Text Available El reconocimiento del conflicto como realidad constitutiva de lo humano y la necesidad de un cierre que pasa por la fijación de la palabra justa encuentran en Hobbes su primera formulación. El pasaje de la instancia retórico-interpretativa a la axiomático-científica se da en Leviatan a través de tres momentos: introspectivo, contractual, estadual; su despliegue permite reconocer a la hermenéutica como resorte imprescindible para la implantación de un orden político fundado en la articulación entre ser (una antropología, decir (una retórica y actuar (una praxis. El intérprete resulta así un operador clave en el ajuste de las instancias natural y político-social

  17. Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Parekh-Olmedo Hetal

    2006-10-01

    Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

  18. Continuous deep sedation, physician-assisted suicide, and euthanasia in Huntington's disorder.

    Science.gov (United States)

    Lindblad, Anna; Juth, Niklas; Fürst, Carl Johan; Lynöe, Niels

    2010-11-01

    To investigate the attitudes among Swedish physicians and the general public towards continuous deep sedation (CDS) as an alternative treatment for a competent, not imminently dying patient with Huntington's disorder requesting physician-assisted suicide (PAS) and euthanasia. A questionnaire was distributed to 1200 physicians in Sweden and 1201 individuals in Stockholm. It consisted of three parts: 1) A vignette about a competent patient with Huntington's disease requesting PAS. When no longer competent, relatives request euthanasia on behalf of the patient. Responders were asked about their attitudes towards these requests and whether CDS would be an acceptable alternative. 2) General questions about PAS and euthanasia. 3) Background variables. The response rate was 56% (physicians) and 52% (general public). The majority of the general public and a fairly large proportion of physicians reported more liberal views on CDS than are expressed in current Swedish and international recommendations. In light of the results, we suggest that there is a need for a broader discussion about the recommendations for CDS, with a special focus on the needs of patients with progressive neurodegenerative disorders.

  19. Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Sidharth Mehan

    2017-01-01

    Full Text Available Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity, resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease-like neurodegeneration.

  20. Double strand DNA breaks response in Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Šolc, Petr; Valášek, Jan; Rausová, Petra; Juhásová, Jana; Juhás, Štefan; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 15-15 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * DNA damage * double strand DNA breaks Subject RIV: FH - Neurology

  1. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Directory of Open Access Journals (Sweden)

    Erik Karl Håkan Clemensson

    Full Text Available The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  2. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Science.gov (United States)

    Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  3. Current status of PET imaging in Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios [King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Camberwell, London (United Kingdom)

    2016-06-15

    To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading ''Huntington Disease'' combined with text and key words ''Huntington Disease'', ''Neuroimaging'' and ''PET''. Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([{sup 18}F]FDG and [{sup 15}O]H{sub 2}O), presynaptic ([{sup 18}F]fluorodopa, [{sup 11}C]β-CIT and [{sup 11}C]DTBZ) and postsynaptic ([{sup 11}C]SCH22390, [{sup 11}C]FLB457 and [{sup 11}C]raclopride) dopaminergic function, phosphodiesterases ([{sup 18}F]JNJ42259152, [{sup 18}F]MNI-659 and [{sup 11}C]IMA107), and adenosine ([{sup 18}F]CPFPX), cannabinoid ([{sup 18}F]MK-9470), opioid ([{sup 11}C]diprenorphine) and GABA ([{sup 11}C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed

  4. Transgenic miniature pig as a model for the study of Huntington´s Disease

    Czech Academy of Sciences Publication Activity Database

    Baxa, Monika

    2012-01-01

    Roč. 22, č. 2 (2012), s. 23-25 ISSN 1210-1737 Institutional support: RVO:67985904 Keywords : transgenic pig * Huntington ´s disease * large animal model * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology

  5. 4p16.3 haplotype modifying age at onset of Huntington disease

    DEFF Research Database (Denmark)

    Nørremølle, A; Budtz-Jørgensen, E; Fenger, K

    2009-01-01

    Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, ...

  6. Juvenile Huntington's disease confirmed by genetic examination in twins Doença de Huntington juvenil confirmada por exame genético em gêmeas

    Directory of Open Access Journals (Sweden)

    GILBERTO LEVY

    1999-09-01

    Full Text Available Early-onset Huntington's disease (HD occurs in approximately 10% of HD's cases. We report juvenile HD in phenotypically identical twins, evaluated by history, clinical and neurologic examination, mini-mental state examination, blood laboratory exams, cerebrospinal fluid examination, skull computed tomography, and genetic examination for HD. Patients had the akinetic-rigid variety (Westphal variant of the disease and paternal inheritance. The laboratory workup confirmed the clinical diagnosis of HD, which adds this report to the rare cases of HD in twins reported in the literature.Doença de Huntington (DH de início precoce ocorre em aproximadamente 10% dos casos de DH. Relatamos DH juvenil em gêmeas fenotipicamente idênticas, avaliadas por história, exames clínico e neurológico, mini-exame do estado mental, exames de sangue, exame do líquido cefalorraquidiano, tomografia computadorizada de crânio e exame genético para DH. As pacientes apresentavam a variedade rígido-acinética (variante de Westphal da doença e herança paterna. A avaliação laboratorial confirmou o diagnóstico clínico de DH, acrescentando-se este relato aos raros casos de DH em gêmeos relatados na literatura.

  7. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P fetal rat lateral ganglionic...

  8. La teoría de la justicia en el estado natural y en el estado político, según Hobbes

    Directory of Open Access Journals (Sweden)

    Fernando Aranda Fraga

    2016-10-01

    Full Text Available El contractualismo explica y justifica el fundamento y la posibilidad de la sociedad a partir de un pacto entre seres libres e iguales. Según Hobbes, los hombres, antes de pactar entre sí, vivían en un estado de guerra de todos contra todos, por tanto carente de justicia. Tampoco había leyes, ni propiedad, ni civilización alguna. En concreto, no existían los derechos, y por tanto era imprescindible buscar una solución eficaz. Deciden por mutuo acuerdo nombrar un garante de sus derechos y obligaciones; entonces nace el Estado y sólo a partir de ese momento queda instaurada la justicia.

  9. Radiation sensitivity of fibroblast strains from patients with Usher's syndrome, Duchenne muscular dystrophy, and Huntington's disease

    International Nuclear Information System (INIS)

    Nove, J.; Little, J.B.; Tarone, R.E.; Robbins, J.H.

    1987-01-01

    The colony-forming ability of 10 normal human fibroblast cell strains and of 10 strains representing 3 degenerative diseases of either nerve or muscle cells was determined after exposure of the cells to X-rays or β-particles from tritiated water. Both methods of irradiation yielded similar comparative results. The fibroblast strains from the 5 Usher's syndrome patients and from 1 of the 2 Huntington's disease patients were hypersensitive to radiation, while those from the 3 Duchenne muscular dystrophy patients and the second Huntington's disease patient had normal sensitivity to radiation. These results indicate both disease-specific and strain-specific differences in the survival of fibroblasts after exposure to ionizing radiation. 38 refs.; 2 figs.; 3 tabs

  10. A new mutation for Huntington disease following maternal transmission of an intermediate allele

    NARCIS (Netherlands)

    Semaka, Alicia; Kay, Chris; Belfroid, René D. M.; Bijlsma, Emilia K.; Losekoot, Monique; van Langen, Irene M.; van Maarle, Merel C.; Oosterloo, Mayke; Hayden, Michael R.; van Belzen, Martine J.

    2015-01-01

    New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (≥ 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the

  11. Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles, Vermont

    Data.gov (United States)

    Vermont Center for Geographic Information — Digital Data from VG95-9A Thompson, PJ�and Thompson, TB, 1995, Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles,...

  12. Magnetic biomineralisation in Huntington's disease transgenic mice

    International Nuclear Information System (INIS)

    Beyhum, W; Hautot, D; Dobson, J; Pankhurst, Q A

    2005-01-01

    The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls

  13. Evidence for Deficits on Different Components of Theory of Mind in Huntington's Disease

    NARCIS (Netherlands)

    Allain, P.; Havel-Thomassin, V.; Verny, C.; Gohier, B.; Lancelot, C.; Besnard, J.; Fasotti, L.; Le Gall, D.

    2011-01-01

    Objective: The main aim of this study was to investigate the effects of Huntington's disease (HD) on cognitive and affective Theory of Mind (ToM) abilities. The relation of ToM performance and executive functions was also examined. Method: Eighteen HD patients, early in the course of the disease,

  14. Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study

    Czech Academy of Sciences Publication Activity Database

    Schuldenzucker, V.; Schubert, R.; Muratori, L. M.; Freisfeld, F.; Rieke, L.; Matheis, T.; Schramke, S.; Motlík, Jan; Kemper, N.; Radespiel, U.; Reilmann, R.

    2017-01-01

    Roč. 12, č. 10 (2017), č. článku e0185970. E-ISSN 1932-6203 Institutional support: RVO:67985904 Keywords : Huntington´s disease * minipigs Subject RIV: EG - Zoology OBOR OECD: Behavioral sciences biology Impact factor: 2.806, year: 2016

  15. Motor, emotional and cognitive deficits in adult BACHD mice : A model for Huntington's disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Rationale: Huntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice

  16. Reversal learning and associative memory impairments in a BACHD rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Ellenbroek, Bart; Schreiber, Rudy

    2013-01-01

    Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the HUNTINGTIN (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently

  17. The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum

    Directory of Open Access Journals (Sweden)

    Abraham Rosas-Arellano

    2018-01-01

    Full Text Available γ-Aminobutyric acid (GABA, plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB, the first one is responsible to render tonic inhibition by pentameric receptors containing α4−6, β3, δ, or ρ1−3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation. On this basis, GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington's disease. Huntington's disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein. For experimental studies of Huntington's disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, as well as YAC128. In all of them, some key experimental reports are focused on neostriatum. The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures, its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively, they display strong expression of many types of GABAA receptors, including tonic subunits. The studies about of GABAA tonic subunits and Huntington's disease into the neostriatum are rising in recent years, suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition, a hallmark of Huntington's disease.

  18. [Predictors of mental and physical quality of life in Huntington's disease].

    Science.gov (United States)

    Brugger, F; Hepperger, C; Hametner, E-M; Holl, A K; Painold, A; Schusterschitz, C; Bonelli, R; Holas, C; Wenning, G K; Poewe, W; Seppi, K

    2015-02-01

    The assessment of health-related quality of life (hrQoL) is an important tool in therapy studies and in the treatment of patients with Huntington's disease (HD). In the absence of causal interventions, HD therapy targets the alleviation of symptoms aiming to improve impaired hrQoL. The aim of this study was to determine the impact of disease characteristics on hrQoL in HD. A total of 80 genetically confirmed HD patients underwent an assessment using the Unified Huntington's Disease Rating Scale, the Beck Depression Inventory, the Hamilton Rating Scale and the SF-36, a scale for the assessment of physical and mental QoL. Multiple regression analysis revealed that health-related physical and mental QoL was considerably influenced by the functional capacity. The mental QoL also correlated with the degree of depressive symptoms, age and the number of CAG repeats. However, there was no statistical relation between QoL and motor and cognitive abilities. This study underlines the relationship between function capacity and depressive symptoms with mental and physical QoL. This is the first time that hrQoL has been investigated in a German speaking cohort. The results are in accordance with previous studies of hrQoL in HD.

  19. Sensory modulation intervention and behaviour support modification for the treatment of severe aggression in Huntington's disease. A single case experimental design.

    Science.gov (United States)

    Fisher, Caroline A; Brown, Anahita

    2017-09-01

    Aggression is common in Huntington's disease. However, at present there are no standard guidelines for managing aggression in Huntington's sufferers due to a lack of empirical research. This paper presents a case study of the treatment of very high levels of aggression with sensory modulation and behaviour support intervention in a Huntington's sufferer. The client exhibited a range of aggressive behaviours, including physical aggression to people, furniture and objects, and verbal aggression. Following an eight week baseline phase, five weeks of sensory modulation intervention were employed. A behaviour support plan was then implemented as an adjunct to the sensory intervention, with aggressive behaviour systematically audited for a further 11 weeks. The results indicate a significant reduction in reported levels of aggression during the combined sensory modulation and behaviour support phase, compared to both the baseline and the sensory modulation therapy alone phases. This case study highlights the efficacy non-pharmacological interventions may have for reducing aggression in HD.

  20. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

    DEFF Research Database (Denmark)

    Metzger, Silke; Walter, Carolin; Riess, Olaf

    2013-01-01

    The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently......, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second...... independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing...

  1. Huntington's disease predictive testing: the case for an assessment approach to requests from adolescents.

    Science.gov (United States)

    Binedell, J; Soldan, J R; Scourfield, J; Harper, P S

    1996-01-01

    Adolescents who are actively requesting Huntington's predictive testing of their own accord pose a dilemma to those providing testing. In the absence of empirical evidence as regards the impact of genetic testing on minors, current policy and guidelines, based on the ethical principles of non-maleficence and respect for individual autonomy and confidentiality, generally exclude the testing of minors. It is argued that adherence to an age based exclusion criterion in Huntington's disease predictive testing protocols is out of step with trends in UK case law concerning minors' consent to medical treatment. Furthermore, contributions from developmental psychology and research into adolescents' decision making competence suggest that adolescents can make informed choices about their health and personal lives. Criteria for developing an assessment approach to such requests are put forward and the implications of a case by case evaluation of competence to consent in terms of clinicians' tolerance for uncertainty are discussed. PMID:8950670

  2. 77 FR 51064 - Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application...

    Science.gov (United States)

    2012-08-23

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,475] Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated May 21, 2012, the State Workforce Office requested administrative reconsideration of the negative...

  3. Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross-Sectional Cohort Study

    Science.gov (United States)

    Piano, Carla; Losurdo, Anna; Della Marca, Giacomo; Solito, Marcella; Calandra-Buonaura, Giovanna; Provini, Federica; Bentivoglio, Anna Rita; Cortelli, Pietro

    2015-01-01

    Study Objectives: To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD). Design: Cross-sectional cohort study. Setting: Sleep laboratory. Patients: Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y). Interventions: Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG). Measurements and Results: The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m2. No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P Marca G, Solito M, Calandra-Buonaura G, Provini F, Bentivoglio AR, Cortelli P. Polysomnographic findings and clinical correlates in Huntington disease: a cross-sectional cohort study. SLEEP 2015;38(9):1489–1495. PMID:25845698

  4. Cross sectional PET study of cerebral adenosine A1 receptors in premanifest and manifest Huntington's disease

    International Nuclear Information System (INIS)

    Matusch, Andreas; Elmenhorst, David; Saft, Carsten; Kraus, Peter H.; Gold, Ralf; Hartung, Hans-Peter; Bauer, Andreas

    2014-01-01

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP ND ) of the A 1 AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [ 18 F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A 1 AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p 1 AR BP ND was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p 1 AR BP ND and years to onset. Before onset of HD, the assumed annual rates of change of A 1 AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  5. Theologico-political Issues in Richard Hooker’s Laws of Ecclesiastical Polity and Thomas Hobbes’s Leviathan Le théologico-politique chez Richard Hooker (Laws of Ecclesiastical Polity et Thomas Hobbes (Leviathan

    Directory of Open Access Journals (Sweden)

    Pierre Lurbe

    2011-04-01

    Full Text Available Hooker et Hobbes ont tous deux été amenés à défendre la suprématie royale contre ses adversaires presbytériens. Une certaine ressemblance de formulation ne doit toutefois pas masquer de profondes divergences, portant à la fois sur l’ampleur de la prérogative royale en matière religieuse et sur la nature de la religion elle-même.

  6. Radiosensitivity in Huntington's disease: implications for pathogenesis and presymptomatic diagnosis

    International Nuclear Information System (INIS)

    Moshell, A.N.; Tarone, R.E.; Barrett, S.F.; Robbins, J.H.

    1980-01-01

    Huntington's disease (HD) is a dominantly inherited fatal disorder characterised by premature death of nerve cells. Cultured lymphocyte lines from four patients with HD were abnormally sensitive to the lethal effects of X rays, as were lines from two of five subjects at risk for HD. The hypersensitivity is specific for ionising radiation, since HD lines had normal survival after exposure to ultraviolet radiation. The hypersensitivity, which may reflect an inherited defect in DNA repair, provides the basis for a presymptomatic diagnostic test for the disease. (author)

  7. Reduced gluconeogenesis and lactate clearance in Huntington's disease

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Signe M B; Campos, André

    2010-01-01

    We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... HD mouse model R6/2 following a lactate challenge, combined with reduced phosphoenolpyruvate carboxykinase and increased pyruvate kinase activity in the mouse liver suggest a reduced capacity...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

  8. Minipig Model of Huntington's Disease: H-1 Magnetic Resonance Spectroscopy of the Brain

    Czech Academy of Sciences Publication Activity Database

    Jozefovičová, M.; Herynek, V.; Jírů, F.; Dezortová, M.; Juhásová, Jana; Juhás, Štefan; Motlík, Jan; Hájek, M.

    2016-01-01

    Roč. 65, č. 1 (2016), s. 155-163 ISSN 0862-8408 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk(CZ) 7F14308; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington´s disease * minipigs * magnetic resonance spectroscopy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016

  9. De la locura y la inseguridad del derecho a la racionalidad y el orden de la ley. Lectura dialéctica de Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Blasco Aznar, Pedro Luis

    2009-12-01

    Full Text Available I take for granted as a starting-point the anthropological antinomy on the individual/social nature of man. This antinomy is constituted politically in Hobbes’ thought as the antinomy individual/society, whose legal expression gives rise to the antinomy right/law —in his iusnaturalist conception— which reflects as well the anthropological antinomy passion/reason. This dialectical conception is only implicit in his political and legal philosophy; however, it becomes obvious if the underlying anthropology is analysed. Therefore, the problems derived from this dialectics require a dialectical solution in accordance with the dialecticity of its anthropological foundation. That is why Hobbes’ legal and political philosophy was not and is not still adequate or effective, but in a partial or negative way.

    Asumo como punto de partida la antinomia antropológica de la naturaleza individual/ social del hombre, que se constituye en el pensamiento de Hobbes, políticamente, como la antinomia indviduo/sociedad, cuya expresión jurídica da lugar a la antinomia derecho/ ley, en su concepción iusnaturalista, que refleja asimismo la antinomia antropológica pasión/razón. Tal concepción dialéctica sólo está implícita en su Filosofía Política y Filosofía del Derecho, pero se hace bien patente si analizamos la antropología subyacente en ella. Por lo tanto, los problemas que esta dialéctica origina requieren una solución o salida dialéctica de acuerdo a la dialecticidad de su fundamento antropológico. Por eso la filosofía jurídica y política de Hobbes no pudo ni puede ser adecuada ni efectiva sino parcial o negativamente.

  10. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...

  11. Contribution of Neuroepigenetics to Huntington's Disease.

    Science.gov (United States)

    Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

    2017-01-01

    Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

  12. 75 FR 11939 - Fisher & Paykel Appliances, Inc., Huntington Beach, CA; Notice of Termination of Investigation

    Science.gov (United States)

    2010-03-12

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-71,749] Fisher & Paykel Appliances, Inc., Huntington Beach, CA; Notice of Termination of Investigation Pursuant to Section 221 of the Trade Act of 1974, as amended, an investigation was initiated in response to a petition filed on July 21...

  13. Entre Carl Schmitt y Thomas Hobbes . Un es tudio del liberalismo moderno a partir del pensamiento de Leo Strauss

    Directory of Open Access Journals (Sweden)

    José Daniel Parra Quintero

    2010-01-01

    Full Text Available El presente ensayo es una lectura sobre el liberalismo moderno desde el pensamiento de Leo Strauss. A partir de su análisis del Concepto de lo político de Carl Schmitt y su crítica de la "despolitización y neutralización" liberal, Strauss responde con una afirmación del problema del derecho natural, para lo cual es fundamental como primer paso estudiar la filosofía política de Thomas Hobbes. Desde allí Strauss se plantea un punto de contraste hacia una consideración clásica del derecho natural que pueda hacer frente al nihilismo político o cosmopolitanismo apolítico en la modernidad tardía, resultado ambos tanto del histori-cismo radical como del positivismo metodológico. Strauss antepone a la afirmación de la voluntad del poder soberano la búsqueda del derecho natural como representación de la idea de la justicia.

  14. Dynamics of the connectome in Huntington's disease: A longitudinal diffusion MRI study

    OpenAIRE

    Odish, Omar F.F.; Caeyenberghs, Karen; Hosseini, Hadi; van den Bogaard, Simon J.A.; Roos, Raymund A.C.; Leemans, Alexander

    2015-01-01

    Abstract Objectives To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data. Experimental design We constructed weighted structural networks and calculated their topological properties. Twenty-two premanifest (preHD), 10 early manifest HD and 24 healthy controls completed baseline and 2 year follow-up scans. We stratified the preHD group based on their predicted years to disease onset into a far...

  15. Structural imaging in premanifest and manifest Huntington disease.

    Science.gov (United States)

    Scahill, Rachael I; Andre, Ralph; Tabrizi, Sarah J; Aylward, Elizabeth H

    2017-01-01

    Huntington disease (HD) neuropathology has a devastating effect on brain structure and consequently brain function; neuroimaging provides a means to assess these effects in gene carriers. In this chapter we first outline the unique utility of structural imaging in understanding HD and discuss some of the acquisition and analysis techniques currently available. We review the existing literature to summarize what we know so far about structural brain changes across the spectrum of disease from premanifest through to manifest disease. We then consider how these neuroimaging findings relate to patient function and nonimaging biomarkers, and can be used to predict disease onset. Finally we review the utility of imaging measures for assessment of treatment efficacy in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  17. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  18. Periodontitis determining the onset and progression of Huntington's disease: review of the literature

    Directory of Open Access Journals (Sweden)

    María Lourdes Rodríguez Coyago

    2015-10-01

    Full Text Available La enfermedad de Hungtinton es un trastorno neurodegenerativo, causado por la expansión de un triplete de citosina, adenina, guanina en el gen de la huntingtina. Se manifiesta con un deterioro físico, cognitivo y psiquiátrico a distintas edades en el adulto, con un pronóstico fatal. Además del número de repeticiones del triplete, existirían otros factores que explicarían el inicio de esta enfermedad a más temprana edad. Se sabe que la neuroinflamación es un protagonista en los trastornos neurodegenerativos, no siendo la enfermedad de Huntington una excepción. La neuroinflamación exacerba el daño neuronal producido por la mutación, al existir activación aberrante de la célula microglía, disfunción de astrocitos y células dendríticas; compromiso de la barrera hematoencefálica y activación de complemento, todas ellas como efecto directo e indirecto de la mutante y otros estímulos como infecciones crónicas. Es el interés del presente trabajo analizar la periodontitis, como modelo de infección bucodental crónica y fuente de inflamación sistémica. Hipotetizamos que el potencial rol de la periodontitis en la enfermedad de Huntington y los mecanismos por los cuales contribuiría a la manifestación temprana y progreso de dicha enfermedad, para lo cual se consideraron revisiones sistemáticas, metanálisis y estudios experimentales publicados tanto en español como en inglés obtenidos del PubMed y SciELO. Son diversos los mecanismos que generan inflamación en el cerebro de estos pacientes, adquiriendo especial protagonismo los mecanismos de la inmunidad innata. Las infecciones buco dentarias crónicas, como la enfermedad periodontal, pueden constituir un factor exacerbante de la neuroinflamación que per se asocia la enfermedad de Huntington.

  19. Do poder à liberdade civil: elementos fundacionais do pensamento político de Thomas Hobbes no Leviatã

    Directory of Open Access Journals (Sweden)

    Raquel Kritsch

    2010-11-01

    Full Text Available O objetivo deste artigo é introduzir os alunos no pensamento político de Thomas Hobbes, tomando como ponto de partida a teoria política por ele desenvolvida no Leviatã, provavelmente sua obra mais conhecida. Partindo-se da categoria mais elementar do pensamento hobbesiano, o poder, à qual se podem reduzir todas as demais relações humanas, aborda-se as noções de estado de natureza, competição, direito, lei, Estado e liberdade, procurando sintetizar ao leitor que se inicia nos clássicos do pensamento político os principais passos lógicos do autor para a construção de sua teoria do Estado bem como seus principais elementos.

  20. Nonparametric estimation for censored mixture data with application to the Cooperative Huntington's Observational Research Trial.

    Science.gov (United States)

    Wang, Yuanjia; Garcia, Tanya P; Ma, Yanyuan

    2012-01-01

    This work presents methods for estimating genotype-specific distributions from genetic epidemiology studies where the event times are subject to right censoring, the genotypes are not directly observed, and the data arise from a mixture of scientifically meaningful subpopulations. Examples of such studies include kin-cohort studies and quantitative trait locus (QTL) studies. Current methods for analyzing censored mixture data include two types of nonparametric maximum likelihood estimators (NPMLEs) which do not make parametric assumptions on the genotype-specific density functions. Although both NPMLEs are commonly used, we show that one is inefficient and the other inconsistent. To overcome these deficiencies, we propose three classes of consistent nonparametric estimators which do not assume parametric density models and are easy to implement. They are based on the inverse probability weighting (IPW), augmented IPW (AIPW), and nonparametric imputation (IMP). The AIPW achieves the efficiency bound without additional modeling assumptions. Extensive simulation experiments demonstrate satisfactory performance of these estimators even when the data are heavily censored. We apply these estimators to the Cooperative Huntington's Observational Research Trial (COHORT), and provide age-specific estimates of the effect of mutation in the Huntington gene on mortality using a sample of family members. The close approximation of the estimated non-carrier survival rates to that of the U.S. population indicates small ascertainment bias in the COHORT family sample. Our analyses underscore an elevated risk of death in Huntington gene mutation carriers compared to non-carriers for a wide age range, and suggest that the mutation equally affects survival rates in both genders. The estimated survival rates are useful in genetic counseling for providing guidelines on interpreting the risk of death associated with a positive genetic testing, and in facilitating future subjects at risk

  1. Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2018-01-01

    Full Text Available Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1, the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.

  2. Insights into gait disorders: walking variability using phase plot analysis, Huntington's disease.

    Science.gov (United States)

    Collett, Johnny; Esser, Patrick; Khalil, Hanan; Busse, Monica; Quinn, Lori; DeBono, Katy; Rosser, Anne; Nemeth, Andrea H; Dawes, Helen

    2014-09-01

    Huntington's disease (HD) is a progressive inherited neurodegenerative disorder. Identifying sensitive methodologies to quantitatively measure early motor changes have been difficult to develop. This exploratory observational study investigated gait variability and symmetry in HD using phase plot analysis. We measured the walking of 22 controls and 35 HD gene carriers (7 premanifest (PreHD)), 16 early/mid (HD1) and 12 late stage (HD2) in Oxford and Cardiff, UK. The unified Huntington's disease rating scale-total motor scores (UHDRS-TMS) and disease burden scores (DBS) were used to quantify disease severity. Data was collected during a clinical walk test (8.8 or 10 m) using an inertial measurement unit attached to the trunk. The 6 middle strides were used to calculate gait variability determined by spatiotemporal parameters (co-efficient of variation (CoV)) and phase plot analysis. Phase plots considered the variability in consecutive wave forms from vertical movement and were quantified by SDA (spatiotemporal variability), SDB (temporal variability), ratio ∀ (ratio SDA:SDB) and Δangleβ (symmetry). Step time CoV was greater in manifest HD (p0.05). Phase plot analysis identified differences between manifest HD and controls for SDB, Ratio ∀ and Δangle (all pplot analysis may be a sensitive method of detecting gait changes in HD and can be performed quickly during clinical walking tests. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Libertad negativa y libre desarrollo de la personalidad en la jurisprudencia constitucional colombiana: un análisis desde la perspectiva de John Stuart Mill y Thomas Hobbes

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Jaramillo

    2013-12-01

    Full Text Available El presente trabajo pretende demostrar que la Corte Constitucional colombiana confunde la noción de libre desarrollo de la personalidad con la noción de libertad negativa, debido a que en el fondo de su argumentación subyace el pensamiento de Thomas Hobbes; situación distinta sería si la Corte fundamentara sus sentencias en el concepto de libertad, desarrollado por John Stuart Mill, quien estaría más acorde con la noción de libre desarrollo de la personalidad bajo los presupuestos de un Estado Social y Democrático de Derecho fundado en la dignidad humana.

  4. The roles of family members, health care workers, and others in decision-making processes about genetic testing among individuals at risk for Huntington disease.

    Science.gov (United States)

    Klitzman, Robert; Thorne, Deborah; Williamson, Jennifer; Marder, Karen

    2007-06-01

    To understand how individuals at risk for Huntington disease view the roles of others, e.g., family members and health care workers, in decision making about genetic testing. Twenty-one individuals (eight mutation-positive, four mutation-negative, and nine not tested) were interviewed for approximately 2 hours each. Interviewees illuminated several key aspects of the roles of family members and health care workers (in genetics and other fields) in decision making about testing that have been underexplored. Family members often felt strongly about whether an individual should get tested. Health care workers provided information and assistance with decision making and mental health referrals that were often helpful. Yet health care workers varied in knowledge and sensitivity regarding testing issues, and the quality of counseling and testing experiences can range widely. At times, health care workers without specialized knowledge of Huntington disease offered opinions of whether to test. Input from families and health care workers could also conflict with each other and with an individual's own preferences. Larger institutional and geographic contexts shaped decisions as well. Decision-making theories applied to Huntington disease testing have frequently drawn on psychological models, yet the current data highlight the importance of social contexts and relationships in testing decisions. This report, the first to our knowledge to explore individuals' perceptions of social factors (particularly family and health care worker involvement) in Huntington disease testing decisions, has critical implications for practice, education, research, and policy.

  5. Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease

    OpenAIRE

    Mealer, Robert G.; Subramaniam, Srinivasa; Snyder, Solomon H.

    2013-01-01

    Although the mutated protein causing Huntington's disease (HD) is expressed throughout the body, the major pathology of HD is localized to the striatum of the brain. We previously reported that the striatal-enriched protein Rhes binds the mutated huntingtin protein and enhances its cytotoxicity. We now demonstrate that Rhes-deleted mice are dramatically protected from neurotoxicity and motor dysfunction in a striatal-specific model of HD elicited by 3-nitropropionic acid. This finding suggest...

  6. Destination and source memory in Huntington's disease.

    Science.gov (United States)

    El Haj, Mohamad; Caillaud, Marie; Verny, Christophe; Fasotti, Luciano; Allain, Philippe

    2016-03-01

    Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults had to put 12 items in a black or a white box (destination task), and to extract another 12 items from a blue or a red box (source task). Afterwards, they had to decide in which box each item had previously been deposited (destination memory), and from which box each item had previously been extracted (source memory). HD participants showed poorer source as well as destination recall performance than healthy adults in the proposed tasks. Correlation analysis showed that destination recall was significantly correlated with episodic recall in HD participants. Destination memory impairment in HD participants seems to be considerably influenced by their episodic memory performance. © 2014 The British Psychological Society.

  7. Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington's Disease Gene-expansion Carriers

    DEFF Research Database (Denmark)

    Unmack Larsen, Ida; Vinther-Jensen, Tua; Gade, Anders

    2015-01-01

    Executive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington's disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS...

  8. Sodium phenylbutyrate in Huntington's disease: a dose-finding study.

    Science.gov (United States)

    Hogarth, Penelope; Lovrecic, Luca; Krainc, Dimitri

    2007-10-15

    Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. 2007 Movement Disorder Society

  9. [Speed of ocular saccades in Huntington disease. Prospective study].

    Science.gov (United States)

    García Ruiz, P J; Cenjor, C; Ulmer, E; Hernández, J; Cantarero, S; Fanjul, S; García de Yébenes, J

    2001-02-01

    Oculomotor abnormalities, especially slow saccades, have long been recognized in Huntington's disease (HD). To study prospectively horizontal saccade velocity by videonystagmography in 21 patients with genetically confirmed HD. The study included a baseline analysis and a second evaluation after 18.8 +/- 7.1 months. We included a control group of 15 subjects. HD group exhibited decreased saccade velocity when compared with that from a control group (for predictive and unpredictive target). HD patients showed decreased saccade velocity with the passage of time (for predictive target, p < 0.01). Finally we found statistical significant correlation between saccade velocity and triplet length. The measurement of saccade velocity might be an objective method to study the natural evolution of HD, and thus evaluate the effectiveness of future therapies.

  10. Study of protein O-GlcNAcylation in the brain tissue in Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Ondrušková, N.; Rodinová, M.; Kratochvílová, H.; Klempíř, J.; Roth, J.; Motlík, Jan; Radoslav, M.; Zeman, J.; Hansíková, H.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 20-20 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk(CZ) 7F14308; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * glycosylation * N-acetylglucosamine Subject RIV: FH - Neurology

  11. Grunting in genetically modified minipig animal model for Huntington ´s disease - a pilot experiment

    Czech Academy of Sciences Publication Activity Database

    Tykalová, T.; Hlavnička, J.; Mačáková, Monika; Baxa, Monika; Cmejla, R.; Motlík, Jan; Klempíř, J.; Rusz, J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 12-13 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * mitochondria * DNA damage Subject RIV: FH - Neurology

  12. Pre-clinical evaluation of AAV5-miHTT gene therapy of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Konstantinová, P.; Miniarikova, J.; Blits, B.; Zimmer, V.; Spoerl, A.; Southwell, A.; Hayden, M.; van Deventer, S.; Deglon, N.; Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Richard, Ch.; Petry, H.

    2015-01-01

    Roč. 78, Supl 2 (2015), s. 8-8 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * gene therapy * AAV5-miHTT Subject RIV: EB - Genetics ; Molecular Biology

  13. El papel de la terapia ocupacional en la enfermedad de Huntington

    OpenAIRE

    Hernández Lozano, David; Fernández Hawrylak, María; Grau Rubio, Claudia

    2014-01-01

    se analiza el papel del terapeuta ocupacional en el trabajo con las personas afectadas por la enfermedad de Huntington. se realizó una investigación por objetivos a través del diseño y puesta en práctica de un programa de intervención encaminado a mitigar el deterioro producido por la enfermedad mediante el entrenamiento en actividades de la vida diaria y de estimulación cognitiva, y a desarrollar competencias en la familia. la investigación se desarrolló en la Asociación de corea de Huntingt...

  14. Internal consistency of a Brazilian version of the unified Huntington's disease rating scale Consistência interna da versão brasileira da escala unificada para avaliação da doença da Huntington

    Directory of Open Access Journals (Sweden)

    Vitor Tumas

    2004-12-01

    Full Text Available We evaluated the reliability of a translated Brazilian version of the Unified Huntington's Disease Rating Scale (UHDRS to establish the reproducibility of the scale in a population that differs substantially from that on which the scale was originally validated. After a training period with the video and guidelines requested from the Huntington Study Group, we applied the UHDRS, except for the cognitive tests, to a group of 21 Brazilian patients with a molecular diagnosis of Huntington's disease (HD. We found a high degree of internal consistency of the motor section of the UHDRS (Cronbach's alpha= 0.841. There was a negative correlation between the total motor score and the functional assessment, the independence scale and the functional capacity. There was a positive correlation between these 3 scales of functional evaluation and a negative correlation between the age of onset of the disease and the number of CAG repeats. The behavioral scale and disease duration were not correlated with any factor. The clinical characteristics of this sample of patients as described by the UHDRS were roughly similar to those reported in the original validation studies and the correlations described were similar to those reported previously. We conclude that the Brazilian version of the UHDRS is reliable and valid to study patients with HD in the Brazilian setting, that this sample of Brazilian patients had clinical characteristics similar to those observed in other world regions, as expected, and that the clinical training method used for the application of the UHDRS was effective to insure a high degree of clinical reproducibility.Nosso estudo avaliou a confiabilidade da versão brasileira da escala unificada para avaliação da doença de Huntington (UHDRS com o objetivo de estabelecer a reprodutibilidade dessa escala em uma população que difere significativamente daquela em que foi originalmente validada. Após um período de treinamento com um v

  15. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  16. Leviatán como pretexto: T Hobbes y la invención moderna de la Razón

    Directory of Open Access Journals (Sweden)

    CARLOS MOYA VALGAÑÓN

    1979-01-01

    Full Text Available T. Hobbes inventó el concepto moderno de estado y el discurso político racional. En Leviatán se equipara razón con gobierno. Se examina la historia occidental que precedió la redacción de Leviatán, comenzando con la cristianización progresiva de los reinos bárbaros. Fue la noción secularizada de razón, en contraposición al reinado de Dios sobre el mundo, la que proporcionó a la burguesía el fundamento epistemológico necesario para su ascensión social. La monarquía absoluta se convirtió en la primera forma del estado moderno. El desarrollo de la imprenta fue el instrumento tecnológico-industrial de la moderna revolución burguesa en la cristiandad occidental. La Reforma Protestante surgió de la nueva libertad para leer libros otrora prohibidos, constituyendo el primer ímpetu para el crecimiento industrial y el desarrollo de la empresa. Así, las revelaciones de la Santa Escritura dieron paso a la investigación científica y a la ciencia moderna.

  17. Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

    International Nuclear Information System (INIS)

    Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A.

    1991-01-01

    Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ( 125 I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease

  18. EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease

    OpenAIRE

    Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

    2012-01-01

    Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...

  19. Hepatic imaging in stage IV-S neuroblastoma

    International Nuclear Information System (INIS)

    Franken, E.A. Jr.; Smith, W.L.; Iowa Univ., Iowa City; Cohen, M.D.; Kisker, C.T.; Platz, C.E.

    1986-01-01

    Stage IV-S neuroblastoma describes a group of infants with tumor spread limited to liver, skin, or bone marrow. Such patients, who constitute about 25% of affected infants with neuroblastoma, may expect spontaneous tumor remission. We report 18 infants with Stage IV-S neuroblastoma, 83% of whom had liver involvement. Imaging investigations included Technetium 99m sulfur colloid scan, ultrasound, and CT. Two patterns of liver metastasis were noted: ill-defined nodules or diffuse tumor throughout the liver. Distinction of normal and abnormal liver with diffuse type metastasis could be quite difficult, particularly with liver scans. We conclude that patients with Stage IV-S neuroblastoma have ultrasound or CT examination as an initial workup, with nuclear medicine scans reserved for followup studies. (orig.)

  20. Thermodynamic data for predicting concentrations of Th(IV), U(IV), Np(IV), and Pu(IV) in geologic environments

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Dhanpat; Roa, Linfeng; Weger, H.T.; Felmy, A.R. [Battelle, Pacific Northwest National Laboratory (PNNL) (United States); Choppin, G.R. [Florida State University (United States); Yui, Mikazu [Waste Isolation Research Division, Tokai Works, Japan Nuclear Cycle Development Inst., Tokai, Ibaraki (Japan)

    1999-01-01

    This report provides thermodynamic data for predicting concentrations of Th(IV), U(IV), Np(IV), and Pu(IV) in geologic environments, and contributes to an integration of the JNC chemical thermodynamic database, JNC-TDB (previously PNC-TDB), for the performance analysis of geological isolation system for high-level radioactive wastes. Thermodynamic data for the formation of complexes or compounds with hydroxide, chloride, fluoride, carbonate, nitrate, sulfate and phosphate are discussed in this report. Where data for specific actinide(IV) species was lacking, the data were selected based on chemical analogy to other tetravalent actinides. In this study, the Pitzer ion-interaction model is used to extrapolate thermodynamic constants to zero ionic strength at 25degC. (author)

  1. Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

    Directory of Open Access Journals (Sweden)

    Liliana B Menalled

    2010-03-01

    Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

  2. About the structure and stability of complex carbonates of thorium (IV), cerium (IV), zirconium (IV), hafnium (IV)

    International Nuclear Information System (INIS)

    Dervin, Jacqueline

    1972-01-01

    This research thesis addressed the study of complex carbonates of cations of metals belonging to the IV A column, i.e. thorium (IV), zirconium (IV), hafnium (IV), and also cerium (IV) and uranium (VI), and more particularly focused on ionic compounds formed in solution, and also on the influence of concentration and nature of cations on stability and nature of the formed solid. The author first presents methods used in this study, discusses their precision and scope of validity. She reports the study of the formation of different complex ions which have been highlighted in solution, and the determination of their formation constants. She reports the preparation and study of the stability domain of solid complexes. The next part reports the use of thermogravimetric analysis, IR spectrometry, and crystallography for the structural study of these compounds

  3. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits.

    Science.gov (United States)

    Righi, Stefania; Galli, Luca; Paganini, Marco; Bertini, Elisabetta; Viggiano, Maria Pia; Piacentini, Silvia

    2016-01-01

    Huntington's disease (HD) primarily affects striatum and prefrontal dopaminergic circuits which are fundamental neural correlates of the timekeeping mechanism. The few studies on HD mainly investigated motor timing performance in second durations. The present work explored time perception in early-to-moderate symptomatic HD patients for seconds and milliseconds with the aim to clarify which component of the scalar expectancy theory (SET) is mainly responsible for HD timing defect. Eleven HD patients were compared to 11 controls employing two separate temporal bisection tasks in second and millisecond ranges. Our results revealed the same time perception deficits for seconds and milliseconds in HD patients. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits. Furthermore, both the non-systematical defect of temporal sensitivity and the main impairment of timing performance in the extreme value of the psychophysical curves suggested an HD deficit in the memory component of the SET. This result was further confirmed by the significant correlations between time perception performance and long-term memory test scores. Our findings added important preliminary data for both a deeper comprehension of HD time-keeping deficits and possible implications on neuro-rehabilitation practices.

  4. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1–60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  5. Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.

    Science.gov (United States)

    Ma, Yanyuan; Wang, Yuanjia

    2014-04-15

    Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members. Copyright © 2013 John Wiley & Sons, Ltd.

  6. The story of George Huntington and his disease

    Directory of Open Access Journals (Sweden)

    Kalyan B Bhattacharyya

    2016-01-01

    Full Text Available George Huntington described some families with choreiform movements in 1872 in the United States of America and since then many such families have been described in other parts of the world and works on the genetics of the disease have brought new vistas in the understanding of the disease. In 1958, Americo Negrette, a young Venezuelan physician observed similar subjects in the vicinity of Lake Maracaibo which was presented by his co-worker, Ramon Avilla Giron at New York in 1972 when United States of America had been commemorating the centenary year of Huntington′s disease. Nancy Wexler, a psychoanalyst, whose mother had been suffering from the disease attended the meeting and organized a research team to Venezuela and they systematically studied more than 18,000 individuals in order to work out a common pedigree. They identified the genetic locus of the disease in the short arm of chromosome 4 and observed that it was a trinucleotide repeat disorder.

  7. Making a measurable difference in advanced Huntington disease care.

    Science.gov (United States)

    Moskowitz, Carol Brown; Rao, Ashwini K

    2017-01-01

    Neurologists' role in the care of people with advanced Huntington disease (HD) (total functional capacity speech and language pathology), behavioral and psychiatric professionals for problem-solving strategies, which must be reviewed with direct care staff before implementation; (3) encourage and support qualitative and quantitative interdisciplinary research studies, and randomized controlled studies of nonpharmacologic interventions; and (4) assist in the development of meaningful measures to further document what works to provide a good quality of life for the patient and family and a comfortable thoughtful approach to a good death. Collaborative models of care depend on: (1) clear communication; (2) ongoing education and support programs; with (3) pharmacologic and rehabilitation interventions, always in the context of respect for the person with HD, a preservation of the individuals' dignity, autonomy, and individual preferences. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Brain atrophy in Huntington's disease: A CT-scan study

    International Nuclear Information System (INIS)

    Starkstein, S.E.; Folstein, S.E.; Brandt, J.; McDonnell, A.; Folstein, M.

    1989-01-01

    CT-scan measurements of cortical and subcortical atrophy were carried out in 34 patients with Huntington's disease (HD). While a significant correlation was observed between parameters of subcortical atrophy (bicaudate ratio, bifrontal ratio and third ventricular ratio) and duration of the disease, there was no significant correlation between these parameters and age. On the other hand, measurements of cortical atrophy (frontal fissure ratio and cortical sulci ratio) correlated significantly with age but not with duration of the disease. When a group of 24 HD patients were compared on CT-scan measurements with a group of 24 age-matched normal controls, significant differences were obtained for all the variables examined, but the bicaudate ratio showed the highest sensitivity and specificity. Even mildly affected patients, with duration of motor symptoms less than 3 years had higher bicaudate ratios than age-matched controls. (orig.)

  9. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  10. Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease

    OpenAIRE

    Keene, C. Dirk; Rodrigues, Cecilia M. P.; Eich, Tacjana; Chhabra, Manik S.; Steer, Clifford J.; Low, Walter C.

    2002-01-01

    Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously r...

  11. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    DEFF Research Database (Denmark)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

    2016-01-01

    The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

  12. Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

    Science.gov (United States)

    Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

  13. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    advanced strategies to develop novel treatments in Huntington's disease are examined. Keywords: Huntington's disease, symptomatic treatment, disease-modifying therapy

  14. A Case of Juvenile Huntington Disease in a 6-Year-Old Boy

    Directory of Open Access Journals (Sweden)

    Jun-Sang Sunwoo

    2010-10-01

    Full Text Available Huntington disease is a neurodegenerative disorder distinguished by the triad of dominant inheritance, choreoathetosis and dementia, usually with onset in the fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine (CAG trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile HD that constitutes about 3% to 10% of all patients is clinically different from adult-onset form and characterized by a larger number of CAG repeats typically exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140 CAG repeats confirmed by molecular genetic analysis.

  15. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    DEFF Research Database (Denmark)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  16. Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Rationale: Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97

  17. Los orígenes filosóficos de la noción de soberanía nacional en el contractualismo político de Thomas Hobbes, John Locke y Jean-Jacques Rousseau

    OpenAIRE

    Vichinkeski Teixeira,Anderson

    2014-01-01

    El artículo examina cómo las proposiciones teóricas de Thomas Hobbes, John Locke y Jean-Jacques Rousseau sobre la función del contrato social han tenido una profunda conexión con la noción de soberanía nacional, desde su fundamentación filosófica hasta sus límites. Para eso, se estudia en los tres filósofos el estado de naturaleza y la concepción de hombre, el proceso de formación del contrato social y la condición del hombre en el Estado, según las formas de Estado y de Gobierno preferidas d...

  18. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

    DEFF Research Database (Denmark)

    Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

    2011-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

  19. Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

    Science.gov (United States)

    Gill, Jaskamal Singh; Jamwal, Sumit; Kumar, Puneet; Deshmukh, Rahul

    2017-04-01

    Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  20. Therapeutic strategies for circadian rhythm and sleep disturbances in Huntington disease.

    Science.gov (United States)

    van Wamelen, Daniel J; Roos, Raymund Ac; Aziz, Nasir A

    2015-12-01

    Aside from the well-known motor, cognitive and psychiatric signs and symptoms, Huntington disease (HD) is also frequently complicated by circadian rhythm and sleep disturbances. Despite the observation that these disturbances often precede motor onset and have a high prevalence, no studies are available in HD patients which assess potential treatments. In this review, we will briefly outline the nature of circadian rhythm and sleep disturbances in HD and subsequently focus on potential treatments based on findings in other neurodegenerative diseases with similarities to HD, such as Parkinson and Alzheimer disease. The most promising treatment options to date for circadian rhythm and sleep disruption in HD include melatonin (agonists) and bright light therapy, although further corroboration in clinical trials is warranted.

  1. Controlled clinical trial of cannabidiol in Huntington's disease.

    Science.gov (United States)

    Consroe, P; Laguna, J; Allender, J; Snider, S; Stern, L; Sandyk, R; Kennedy, K; Schram, K

    1991-11-01

    Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.

  2. Swallowing endoscopy findings in Huntington's disease: a case report.

    Science.gov (United States)

    Alves, Thaís Coelho; Cola, Paula Cristina; Santos, Rarissa Rúbia Dallaqua Dos; Motonaga, Suely Mayumi; Silva, Roberta Gonçalves da

    2016-01-01

    Huntington's disease (HD) is a degenerative genetic disorder with autosomal-dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study.

  3. Altered selenium status in Huntington's disease: neuroprotection by selenite in the N171-82Q mouse model.

    Science.gov (United States)

    Lu, Zhen; Marks, Eileen; Chen, Jianfang; Moline, Jenna; Barrows, Lorraine; Raisbeck, Merl; Volitakis, Irene; Cherny, Robert A; Chopra, Vanita; Bush, Ashley I; Hersch, Steven; Fox, Jonathan H

    2014-11-01

    Disruption of redox homeostasis is a prominent feature in the pathogenesis of Huntington's disease (HD). Selenium an essential element nutrient that modulates redox pathways and has been reported to provide protection against both acute neurotoxicity (e.g. methamphetamine) and chronic neurodegeneration (e.g. tauopathy) in mice. The objective of our study was to investigate the effect of sodium selenite, an inorganic form of selenium, on behavioral, brain degeneration and biochemical outcomes in the N171-82Q Huntington's disease mouse model. HD mice, which were supplemented with sodium selenite from 6 to 14 weeks of age, demonstrated increased motor endurance, decreased loss of brain weight, decreased mutant huntingtin aggregate burden and decreased brain oxidized glutathione levels. Biochemical studies revealed that selenite treatment reverted HD-associated changes in liver selenium and plasma glutathione in N171-82Q mice and had effects on brain selenoprotein transcript expression. Further, we found decreased brain selenium content in human autopsy brain. Taken together, we demonstrate a decreased selenium phenotype in human and mouse HD and additionally show some protective effects of selenite in N171-82Q HD mice. Modification of selenium metabolism results in beneficial effects in mouse HD and thus may represent a therapeutic strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease.

    Science.gov (United States)

    Mason, Sarah L; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S; Rowe, James B; Barker, Roger A; Hampshire, Adam

    2015-04-01

    Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, pneural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis

  5. Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

    Czech Academy of Sciences Publication Activity Database

    Křížová, J.; Štufková, H.; Rodinová, M.; Mačáková, Monika; Bohuslavová, Božena; Vidinská, Daniela; Klíma, Jiří; Ellederová, Zdeňka; Pavlok, Antonín; Howland, D. S.; Zeman, J.; Motlík, Jan; Hansíková, H.

    2017-01-01

    Roč. 17, 4-5 (2017), s. 213-226 ISSN 1660-2854 R&D Projects: GA MŠk 7F14308; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : Huntington disease * large animal model * mutant huntingtin Subject RIV: EA - Cell Biology OBOR OECD: Cell biology Impact factor: 2.842, year: 2016

  6. Transgenic Rat Model of Huntington's Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients.

    Czech Academy of Sciences Publication Activity Database

    Mazurová, Y.; Anděrová, Miroslava; Němečková, I.; Bezrouk, A.

    2014-01-01

    Roč. 2014, Aug 03 (2014), s. 291531 ISSN 2314-6133 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:GA MŠk(CZ) Prvouk P37 Institutional support: RVO:68378041 Keywords : Huntington's Disease * neurodegenerative process in the brain Subject RIV: FH - Neurology Impact factor: 1.579, year: 2014

  7. Assessing and Modulating Kynurenine Pathway Dynamics in Huntington's Disease: Focus on Kynurenine 3-Monooxygenase.

    Science.gov (United States)

    Sathyasaikumar, Korrapati V; Breda, Carlo; Schwarcz, Robert; Giorgini, Flaviano

    2018-01-01

    The link between disturbances in kynurenine pathway (KP) metabolism and Huntington's disease (HD) pathogenesis has been explored for a number of years. Several novel genetic and pharmacological tools have recently been developed to modulate key regulatory steps in the KP such as the reaction catalyzed by the enzyme kynurenine 3-monooxygenase (KMO). This insight has offered new options for exploring the mechanistic link between this metabolic pathway and HD, and provided novel opportunities for the development of candidate drug-like compounds. Here, we present an overview of the field, focusing on some novel approaches for interrogating the pathway experimentally.

  8. Decreased mitochondrial density and ultrastructural changes of mitochondria in cultivated skin fibroblasts of patients with Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Rodinová, M.; Marková, M.; Kratochvílová, H.; Kučerová, I.; Tesařová, M.; Lišková, Irena; Klempíř, J.; Roth, J.; Zeman, J.; Hansíková, H.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 20-21 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * fibroblasts * mitochondrial ultrastructure Subject RIV: FH - Neurology

  9. Haplotype-based stratification of Huntington's disease.

    Science.gov (United States)

    Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2017-11-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

  10. Huntington Disease - principles and practice of nutritional management.

    Science.gov (United States)

    Zukiewicz-Sobczak, Wioletta; Król, Renata; Wróblewska, Paula; Piątek, Jacek; Gibas-Dorna, Magdalena

    2014-01-01

    Huntington disease (HD) is a degenerative brain disease clinically manifested by the characteristic triad: physical symptoms including involuntary movements and poor coordination, cognitive changes with less ability to organize routine tasks, and some emotional and behavioral disturbances. For patients with HD, feeding is one of the problems they have to face. People with HD often have lower than average body weight and struggle with malnutrition. As a part of therapy, good nutrition is an intervention maintaining health and functional ability for maximally prolonged time. In the early stages of HD, small amounts of blenderized foods given orally are recommended. In more advanced stages, enteral nutrition is essential using gastric, or jejunal tubes for short term. Most severe cases require gastrostomy or gastrojejunostomy. Although enteral feeding is well tolerated by most of the patients, a number of complications may occur, including damage to the nose, pharynx, or esophagus, aspiration pneumonia, sinusitis, metabolic imbalances due to improper nutrient and fluid supply, adverse effects affecting gastrointestinal system, and refeeding syndrome. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV

    Science.gov (United States)

    Chu, Yiting; Lai, Mark H. C.; Xu, Yining; Zhou, Yuanyuan

    2012-01-01

    The authors review the "Advanced Clinical Solutions for WAIS-IV and WMS-IV". The "Advanced Clinical Solutions (ACS) for the Wechsler Adult Intelligence Scale-Fourth Edition" (WAIS-IV; Wechsler, 2008) and the "Wechsler Memory Scale-Fourth Edition" (WMS-IV; Wechsler, 2009) was published by Pearson in 2009. It is a…

  12. Direct complexonometric determination of thorium (IV), uranium (IV), neptunium (IV), plutonium (IV) by titration of diethylenetriaminepentaacetic acid with xylenol orange as indicator

    International Nuclear Information System (INIS)

    Rykov, A.G.; Piskunov, E.M.; Timofeev, G.A.

    1975-01-01

    The purpose of the present work was to develop a method of determining Th(IV), U(IV), Np(N) and Pu(IV) in acid solutions by titration with diethylenetriamine pentacetic acid, the indicator being xylenol orange. It has been established that Th, U, Np and Pu can be determined to within 0.5-1.5%. Th and U in quantities of tens of milligrams can be determined with greater accuracy, attaining hundredths of one per cent. During titration the determination is not hindered by singly- and doubly-charged metal ions, trivalent lanthanides and actinides, except plutonium. The proposed method can be used to determine U(IV) in the presence of considerable quantities of U(VI) and Np(IV) in the presence of Np(V). Total concentrations of uranium or neptunium are determined by reducing uranium (VI) or neptunium (V) by a standard method (for example, using metallic lead, cadmium or zinc amalgam) to the tetravalent state and applying the method described in the paper. (E.P.)

  13. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel

    2015-01-01

    age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample......Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim...... of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms...

  14. Cross sectional PET study of cerebral adenosine A{sub 1} receptors in premanifest and manifest Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas; Elmenhorst, David [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Saft, Carsten; Kraus, Peter H.; Gold, Ralf [St. Josef Hospital, Ruhr University Bochum, Department of Neurology, Huntington Centre NRW, Bochum (Germany); Hartung, Hans-Peter [Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany); Bauer, Andreas [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany)

    2014-06-15

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP{sub ND}) of the A{sub 1}AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [{sup 18} F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A{sub 1}AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p <.01, in the thalamus on average). Across stages a successive reduction of A{sub 1}AR BP{sub ND} was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p <.01, in the caudatus and amygdala. There was a strong correlation between A{sub 1}AR BP{sub ND} and years to onset. Before onset of HD, the assumed annual rates of change of A{sub 1}AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  15. Stimulating neural plasticity with real-time fMRI neurofeedback in Huntington's disease: A proof of concept study.

    Science.gov (United States)

    Papoutsi, Marina; Weiskopf, Nikolaus; Langbehn, Douglas; Reilmann, Ralf; Rees, Geraint; Tabrizi, Sarah J

    2018-03-01

    Novel methods that stimulate neuroplasticity are increasingly being studied to treat neurological and psychiatric conditions. We sought to determine whether real-time fMRI neurofeedback training is feasible in Huntington's disease (HD), and assess any factors that contribute to its effectiveness. In this proof-of-concept study, we used this technique to train 10 patients with HD to volitionally regulate the activity of their supplementary motor area (SMA). We collected detailed behavioral and neuroimaging data before and after training to examine changes of brain function and structure, and cognitive and motor performance. We found that patients overall learned to increase activity of the target region during training with variable effects on cognitive and motor behavior. Improved cognitive and motor performance after training predicted increases in pre-SMA grey matter volume, fMRI activity in the left putamen, and increased SMA-left putamen functional connectivity. Although we did not directly target the putamen and corticostriatal connectivity during neurofeedback training, our results suggest that training the SMA can lead to regulation of associated networks with beneficial effects in behavior. We conclude that neurofeedback training can induce plasticity in patients with Huntington's disease despite the presence of neurodegeneration, and the effects of training a single region may engage other regions and circuits implicated in disease pathology. © 2017 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  16. Cognitive change in patients with Huntington disease on the Repeatable Battery for the Assessment of Neuropsychological Status.

    Science.gov (United States)

    Beglinger, Leigh J; Duff, Kevin; Allison, Jessica; Theriault, Danielle; O'Rourke, Justin J F; Leserman, Anne; Paulsen, Jane S

    2010-07-01

    Huntington disease (HD) is a neurodegenerative disease associated with cognitive, motor, and psychiatric deterioration over time. Although there is currently no cure for HD, there has been a surge of clinical trials available to patients with HD over the past 5 years. However, cognitive measures have generally been lacking from these trials. A brief, repeatable neuropsychological battery is needed to assess cognitive endpoints. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may be useful for assessing change in interventional studies or for clinical monitoring. A total of 38 patients with HD were assessed using the RBANS, other cognitive tests, and the standardized HD battery (Unified Huntington's Disease Rating Scale, UHDRS) at two clinic visits approximately 16 months apart. The RBANS Attention Index, as well as individual subtest scores on Coding, Digit Span, List Recognition, Figure Copy, and Figure Recall all declined significantly over this interval. Performance on the UHDRS cognitive tests (Symbol Digit Modalities; Stroop Color, and Stroop Word) also declined, as did functional capacity. Results suggest that cognitive changes were detected both on established cognitive tasks used in HD research and on the RBANS in patients with measurable functional decline. The RBANS provided additional information about other cognitive domains affected (e.g., memory) and may be a useful measure for tracking longitudinal change.

  17. The functional implications of motor, cognitive, psychiatric, and social problem-solving states in Huntington's disease.

    Science.gov (United States)

    Van Liew, Charles; Gluhm, Shea; Goldstein, Jody; Cronan, Terry A; Corey-Bloom, Jody

    2013-01-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal relationships, judgment, and independent living. The aim of the present study was to examine social problem-solving (SPS) in well-characterized HD and at-risk (AR) individuals and to examine its unique and conjoint effects with motor, cognitive, and psychiatric states on functional ratings. Sixty-three participants, 31 HD and 32 gene-positive AR, were included in the study. Participants completed the Social Problem-Solving Inventory-Revised: Long (SPSI-R:L), a 52-item, reliable, standardized measure of SPS. Items are aggregated under five scales (Positive, Negative, and Rational Problem-Solving; Impulsivity/Carelessness and Avoidance Styles). Participants also completed the Unified Huntington's Disease Rating Scale functional, behavioral, and cognitive assessments, as well as additional neuropsychological examinations and the Symptom Checklist-90-Revised (SCL-90R). A structural equation model was used to examine the effects of motor, cognitive, psychiatric, and SPS states on functionality. The multifactor structural model fit well descriptively. Cognitive and motor states uniquely and significantly predicted function in HD; however, neither psychiatric nor SPS states did. SPS was, however, significantly related to motor, cognitive, and psychiatric states, suggesting that it may bridge the correlative gap between psychiatric and cognitive states in HD. SPS may be worth assessing in conjunction with the standard gamut of clinical assessments in HD. Suggestions for future research and implications for patients, families, caregivers, and clinicians are discussed.

  18. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2.

    Science.gov (United States)

    Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne; Josefsen, Knud

    2015-04-20

    Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

  19. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

    2016-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

  20. O mito das Olimpíadas: Hesíodo, Bacon, Hobbes e a infindável luta dos titãs

    Directory of Open Access Journals (Sweden)

    Luiz Carlos Santos da Silva

    2016-08-01

    Full Text Available O presente artigo tem por objetivo apresentar alguns dos aspectos mitológicos que fundamentam a realização das olimpíadas desde a antiguidade grega, particularmente a “corrida de tochas acessas” que atualmente inaugura a abertura dos jogos. Para tanto, buscamos apresentar alguns relatos que narram a realização dos jogos olímpicos como uma espécie memória aos mitos fundadores da cultura grega. Nesse registro, consideramos alguns aspectos das narrativas de Hesíodo sobre o mito de Prometeu, bem como algumas observações de filósofos modernos como Francis Bacon e Thomas Hobbes sobre como essa fábula narra a interpretação de uma condição humana fundada em uma competição análoga à uma interminável luta de titãs. Condição humana essa oriunda da desobediência às vontades dos deuses do Olimpo, cristalizada na expressão de uma cultura da competição que visa não apenas agradar a esses deuses, detentores do poder no Olimpo, mas também igualar certos homens a eles.

  1. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  2. Congenital bilateral neuroblastoma (stage IV-S): case report

    International Nuclear Information System (INIS)

    Lee, Jeong Hee; Lee, Hee Jung; Woo, Seong Ku; Lee, Sang Rak; Kim, Heung Sik

    2002-01-01

    Congenital neonatal neuroblastoma is not uncommon but bilateral adrenal neuroblastoma is rare, accounting for about ten percent of neuroblastomas in children. We report the US the MR findings of a stage IV-S congenital bilateral neuroblastoma occurring in a one-day-old neonate

  3. Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Starkstein, S.E.; Brandt, J.; Bylsma, F.; Peyser, C.; Folstein, M.; Folstein, S.E.

    1992-01-01

    Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: A memory/speed-of-processing factor, a 'frontal' factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the 'frontal' or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD. (orig.)

  4. Social Cognition, Executive Functions and Self-Report of Psychological Distress in Huntington's Disease

    DEFF Research Database (Denmark)

    Larsen, Ida Unmack; Vinther-Jensen, Tua; Nielsen, Jørgen Erik

    2016-01-01

    OBJECTIVE: Huntington's disease (HD) is characterized by motor symptoms, psychiatric symptoms and cognitive impairment in, inter alia, executive functions and social cognition. The aim of this study was to investigate the relationship between subjective feeling of psychological distress using...... a self-report questionnaire and performances on tests of executive functions and social cognition in a large consecutive cohort of HD patients. METHOD: 50 manifest HD patients were tested in social cognition and executive functions and each answered a self-report questionnaire about current status...... psychological distress was significantly associated with worse performances on social cognitive tests (mean absolute correlation .34) and that there were no significant correlations between perceived psychological distress and performance on tests of executive functions. The correlations between perceived...

  5. Medical management of motor manifestations of Huntington disease.

    Science.gov (United States)

    McCusker, Elizabeth A; Loy, Clement T

    2017-01-01

    The motor and movement disorders of Huntington disease (HD) are managed in the context of the other disease features. Chorea and dystonia are the most common HD-associated movement disorders, and they can be assessed on research rating scales. However other motor manifestations have a significant impact. In particular, dysphagia influences choice and tolerance of treatment for the movement disorder, as will comorbidities, patient awareness, and distress related to the motor feature or movement. Treatment for other disease features may aggravate the motor disorder, e.g., increased swallowing difficulty associated with antipsychotic agents. Basic principles in deciding to institute a treatment are outlined as well as treatment of specific motor manifestations and movements. There is a paucity of evidence to support the treatments available for the motor disorder, with only one agent with class 1 evidence, tetrabenazine, for chorea. There are, however, treatments informed by expert opinion which reflect the management of a wider HD phenotype than that represented in clinical trials. Some treatments are based on evidence from use in other conditions. Medical management is usually undertaken later in the disease with concurrent nonmedical interventions after multidisciplinary assessments. Medication review with HD progression is essential. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Science.gov (United States)

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  7. Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly.

    Science.gov (United States)

    Kumar, Amit; Ratan, Rajiv R

    2016-10-01

    Redox homeostasis is crucial for proper cellular functions, including receptor tyrosine kinase signaling, protein folding, and xenobiotic detoxification. Under basal conditions, there is a balance between oxidants and antioxidants. This balance facilitates the ability of oxidants, such as reactive oxygen species, to play critical regulatory functions through a direct modification of a small number of amino acids (e.g. cysteine) on signaling proteins. These signaling functions leverage tight spatial, amplitude, and temporal control of oxidant concentrations. However, when oxidants overwhelm the antioxidant capacity, they lead to a harmful condition of oxidative stress. Oxidative stress has long been held to be one of the key players in disease progression for Huntington's disease (HD). In this review, we will critically review this evidence, drawing some intermediate conclusions, and ultimately provide a framework for thinking about the role of oxidative stress in the pathophysiology of HD.

  8. Cognitive and behavioral changes in Huntington disease before diagnosis.

    Science.gov (United States)

    Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

    2017-01-01

    Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Care of patients with Huntington's disease in South America: a survey

    Directory of Open Access Journals (Sweden)

    Ricardo Oliveira Horta Maciel

    2013-06-01

    Full Text Available Huntington's disease (HD is a rare neurodegenerative disease with a multitude of symptoms, which requires access to specialized multidisciplinary care for adequate management. The aim of this study was to survey the characteristics of care in various HD centers in South America (SA. Methods A questionnaire was sent to 24 centers involved in the care for HD patients in SA. Results Of the total 24 centers, 19 (79.2% are academic units. The majority of centers (62.5% are general movement disorders clinics. Multidisciplinary care is available in 19 (79.2% centers and in 20 (83.3% care is provided free of charge. Genetic testing and counseling are available in 25 and 66.6% of centers, respectively. The majority of centers (83.3% have no institutional support for end-stage care. Conclusions Although HD centers in SA are committed to providing multidisciplinary care, access to genetic counseling and end-stage care are lacking in most centers.

  10. Is gardening a stimulating activity for people with advanced Huntington's disease?

    Science.gov (United States)

    Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

    2014-11-01

    This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. Gardening with Huntington's disease clients--creating a programme of winter activities.

    Science.gov (United States)

    Spring, Josephine Anne; Baker, Mark; Dauya, Loreane; Ewemade, Ivie; Marsh, Nicola; Patel, Prina; Scott, Adrienne; Stoy, Nicholas; Turner, Hannah; Viera, Marc; Will, Diana

    2011-01-01

    A programme of garden-related indoor activities was developed to sustain a gardening group for people with mid to late stage Huntington's disease during the winter. The activities were devised by the horticulturist, working empirically, involving the services occupational therapist, physiotherapist, occupational therapy art technician, computer room, recreation and leisure staff. The programme was strongly supported by the nursing and care staff. Feedback on the effectiveness of the activities was sought from the clients, team members and unit staff. The clients' interest in gardening was sustained by a multidisciplinary programme of indoor growing and using plant products in creative activities, computing and group projects. The clients enjoyed all activities except one that they said lacked contact with plants. The inexpensive programme of activities enabled creativity and self-expression, stimulated social contact and helped with therapeutic goals of the clients. In addition, it engaged the multi-disciplinary team and the unit staff, was practical and enhanced the environment.

  12. Oxochloroalkoxide of the Cerium (IV and Titanium (IV as oxides precursor

    Directory of Open Access Journals (Sweden)

    Machado Luiz Carlos

    2002-01-01

    Full Text Available The Cerium (IV and Titanium (IV oxides mixture (CeO2-3TiO2 was prepared by thermal treatment of the oxochloroisopropoxide of Cerium (IV and Titanium (IV. The chemical route utilizing the Cerium (III chloride alcoholic complex and Titanium (IV isopropoxide is presented. The compound Ce5Ti15Cl16O30 (iOPr4(OH-Et15 was characterized by elemental analysis, FTIR and TG/DTG. The X-ray diffraction patterns of the oxides resulting from the thermal decomposition of the precursor at 1000 degreesC for 36 h indicated the formation of cubic cerianite (a = 5.417Å and tetragonal rutile (a = 4.592Å and (c = 2.962 Å, with apparent crystallite sizes around 38 and 55nm, respectively.

  13. Transuranium perrhenates: Np(IV), Pu(IV) and (III), Am (III)

    International Nuclear Information System (INIS)

    Silvestre, Jean-Paul; Freundlich, William; Pages, Monique

    1977-01-01

    Synthesis in aqueous solution and by solid state reactions, crystallographical characterization and study of the stability of some transuranium perrhenates: Asup(n+)(ReO 4 - )sub(n) (A=Np(IV), Pu(IV), Pu(III), Am(III) [fr

  14. Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne

    2010-01-01

    The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine....... The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease...

  15. Características del habla, el lenguaje y la deglución en la enfermedad de Huntington

    OpenAIRE

    Camargo-Mendoza, Maryluz; Castillo-Triana, Nicolás; Fandiño-Cardona, Juan Miguel; Mateus-Moreno, Angélica; Moreno-Martínez, Mariana

    2017-01-01

    Resumen La enfermedad de Huntington (EH) ha sido descrita como una afección de causa genética producida por una mutación en la repetición de la secuencia de nucleótidos CAG (citosina-adenina-guanina). Según el estadio que curse la enfermedad, las personas pueden presentar dificultades en el habla, el lenguaje y la deglución. El propósito de este artículo es exponer con detalle dichas dificultades, así como su tratamiento fonoaudiológico. Se destaca que en el habla se encuentran característica...

  16. Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease.

    Science.gov (United States)

    Koga, Hiroshi; Martinez-Vicente, Marta; Arias, Esperanza; Kaushik, Susmita; Sulzer, David; Cuervo, Ana Maria

    2011-12-14

    Autophagy contributes to the removal of prone-to-aggregate proteins, but in several instances these pathogenic proteins have been shown to interfere with autophagic activity. In the case of Huntington's disease (HD), a congenital neurodegenerative disorder resulting from mutation in the huntingtin protein, we have previously described that the mutant protein interferes with the ability of autophagic vacuoles to recognize cytosolic cargo. Growing evidence supports the existence of cross talk among autophagic pathways, suggesting the possibility of functional compensation when one of them is compromised. In this study, we have identified a compensatory upregulation of chaperone-mediated autophagy (CMA) in different cellular and mouse models of HD. Components of CMA, namely the lysosome-associated membrane protein type 2A (LAMP-2A) and lysosomal-hsc70, are markedly increased in HD models. The increase in LAMP-2A is achieved through both an increase in the stability of this protein at the lysosomal membrane and transcriptional upregulation of this splice variant of the lamp-2 gene. We propose that CMA activity increases in response to macroautophagic dysfunction in the early stages of HD, but that the efficiency of this compensatory mechanism may decrease with age and so contribute to cellular failure and the onset of pathological manifestations.

  17. Huntington's disease in Greece: the experience of 14 years.

    Science.gov (United States)

    Panas, M; Karadima, G; Vassos, E; Kalfakis, N; Kladi, A; Christodoulou, K; Vassilopoulos, D

    2011-12-01

    A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process. © 2010 John Wiley & Sons A/S.

  18. Coordination and solvent extraction behaviour of oxozirconium(IV), thorium(IV) and dioxouranium(VI)

    International Nuclear Information System (INIS)

    Dash, K.C.

    1989-01-01

    The systematic liquid-liquid extraction behaviour of oxozirconium (IV), thorium(IV) and dioxouranium(VI) have been investigated using a number of synthesised and commercial chelating extractants. The synergism or antagonism for these processes in presence of neutral donor ligands have also been identified and the conditions for separation and isolation of pure individual metal ions have been established. The coordination behaviour of oxozirconium(IV), thorium(IV) and dioxouranium(VI) with a large number of mono- and polydentate ligands have been studied. With oxozirconium(IV), invariably always a cyclic, tetranuclear species is obtained, derived from the tetrameric structure of the parent ZrOCl 2 .8H 2 O which is actually (Zr 4 (OH) 8 (H 2 O) 16 )Cl 8 .12H 2 O. No simple, monomeric oxozirconium(IV) complex was obtained. Uranium(VI) and thorium(IV) form a wide variety of complexes of higher coordination numbers and several bi- and trinuclear complexes were also characterised where the two adjacent metal centres are joined to each other by a double hydroxo-bridge. (author). 69 refs., 3 figs., 4 tabs

  19. Reduction of IFNα and IL-10 in central nervous system and increase in peripheral IL-8 in transgenic porcine Huntington´s disease model

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Valeková, Ivona; Jarkovská, Karla; Kotrčová, Eva; Motlík, Jan; Gadher, S. J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 10-11 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : porcine Huntington ´s disease model * IFNα * IL-10 Subject RIV: EB - Genetics ; Molecular Biology

  20. Care of patients with Huntington's disease in South America: a survey Cuidado de pacientes com doença de Huntington na América do Sul: um inquérito

    Directory of Open Access Journals (Sweden)

    Ricardo Oliveira Horta Maciel

    2013-06-01

    Full Text Available Huntington's disease (HD is a rare neurodegenerative disease with a multitude of symptoms, which requires access to specialized multidisciplinary care for adequate management. The aim of this study was to survey the characteristics of care in various HD centers in South America (SA. Methods A questionnaire was sent to 24 centers involved in the care for HD patients in SA. Results Of the total 24 centers, 19 (79.2% are academic units. The majority of centers (62.5% are general movement disorders clinics. Multidisciplinary care is available in 19 (79.2% centers and in 20 (83.3% care is provided free of charge. Genetic testing and counseling are available in 25 and 66.6% of centers, respectively. The majority of centers (83.3% have no institutional support for end-stage care. Conclusions Although HD centers in SA are committed to providing multidisciplinary care, access to genetic counseling and end-stage care are lacking in most centers. A doença de Huntington (DH é uma doença neurodegenerativa rara que requer tratamento multidisciplinar especializado para manejo adequado. O objetivo do presente trabalho foi pesquisar as características da assistência à saúde em centros de DH na América do Sul (AS. Métodos Um questionário foi enviado para 24 centros envolvidos no cuidado de pacientes com DH na AS. Resultados Dos 24 centros, 19 (79,2% são unidades acadêmicas. A maioria (62,5% são clínicas de distúrbios dos movimentos. Cuidado multidisciplinar é disponível em 19 (79,2% dos centros e em 20 (83,3%, o tratamento é gratuito. O teste e o aconselhamento genético estão disponíveis em 25 e 66,6% dos centros, respectivamente. Não há suporte institucional para cuidado terminal em 83,3% dos centros. Conclusões Apesar dos centros de DH na AS terem compromisso com o provimento de cuidados multidisciplinares, o acesso a aconselhamento genético e a tratamento na fase terminal são falhos na maioria dos centros.

  1. Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

    DEFF Research Database (Denmark)

    Nielsen, Signe Marie Borch; Vinther-Jensen, Tua; Nielsen, Jørgen E.

    2016-01-01

    dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest......Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- A nd cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular...... and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity...

  2. Early grey matter changes in structural covariance networks in Huntington's disease.

    Science.gov (United States)

    Coppen, Emma M; van der Grond, Jeroen; Hafkemeijer, Anne; Rombouts, Serge A R B; Roos, Raymund A C

    2016-01-01

    Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD. We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. Structural magnetic resonance imaging data of premanifest HD ( n  = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed. Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p  covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

  3. Synthesis and characterization of chiral thorium(IV) and uranium(IV) benzamidinate complexes

    Energy Technology Data Exchange (ETDEWEB)

    Schoene, Sebastian; Maerz, Juliane; Kaden, Peter; Patzschke, Michael; Ikeda-Ohno, Atsushi [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Chemistry of the F-Elements

    2017-06-01

    Two chiral benzamidinate complexes of tetravalent actinides (Th(IV) and U(IV)) were synthesized using a salt metathesis reaction of the corresponding actinide(IV) tetrachlorides and the potassium salt of the chiral benzamidine (S,S)-N,N-Bis-(1-phenylethyl)-benzamidine ((S)-HPEBA). The structure of the complexes was determined with single crystal X-ray diffraction. These are the first examples of chiral amidinate complexes of actinides.

  4. Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington's disease model

    DEFF Research Database (Denmark)

    Reynolds, Regina Hertfelder; Petersen, Maria Hvidberg; Willert, Cecilie Wennemoes

    2018-01-01

    The three factors, p53, the microRNA-34 family and Sirtuin 1 (SIRT1), interact in a positive feedback loop involved in cell cycle progression, cellular senescence and apoptosis. Each factor in this triad has roles in metabolic regulation, maintenance of mitochondrial function, and regulation...... of brain-derived neurotrophic factor (BDNF). Thus, this regulatory network holds potential importance for the pathophysiology of Huntington's disease (HD), an inherited neurodegenerative disorder in which both mitochondrial dysfunction and impaired neurotrophic signalling are observed. We investigated...

  5. iväkoti Riemula

    OpenAIRE

    Alanko, Reetta; Ihanamäki, Katja

    2012-01-01

    Opinnäytetyössä kuvataan yleisesti päivähoidon kehitystä Suomessa sekä päivähoitoa yrittäjän näkökulmasta, tuoden esille sen tämän päivän haasteet ja mahdollisuudet. Työssä on pohdittu yhteistyön merkitystä kunnan kanssa ja sitä, miten kunta voi osaltaan joko rajoittaa tai edesauttaa yksityisen päivähoitoyrityksen toimintaa. Opinnäytetyössä kerrotaan teoriassa Päiväkoti Riemula nimisen, erityispäivähoitopalveluita tarjoavan yrityksen perustamiseen liittyvistä suunnitelmista. Suunnitelluss...

  6. Total recognition discriminability in Huntington's and Alzheimer's disease.

    Science.gov (United States)

    Graves, Lisa V; Holden, Heather M; Delano-Wood, Lisa; Bondi, Mark W; Woods, Steven Paul; Corey-Bloom, Jody; Salmon, David P; Delis, Dean C; Gilbert, Paul E

    2017-03-01

    Both the original and second editions of the California Verbal Learning Test (CVLT) provide an index of total recognition discriminability (TRD) but respectively utilize nonparametric and parametric formulas to compute the index. However, the degree to which population differences in TRD may vary across applications of these nonparametric and parametric formulas has not been explored. We evaluated individuals with Huntington's disease (HD), individuals with Alzheimer's disease (AD), healthy middle-aged adults, and healthy older adults who were administered the CVLT-II. Yes/no recognition memory indices were generated, including raw nonparametric TRD scores (as used in CVLT-I) and raw and standardized parametric TRD scores (as used in CVLT-II), as well as false positive (FP) rates. Overall, the patient groups had significantly lower TRD scores than their comparison groups. The application of nonparametric and parametric formulas resulted in comparable effect sizes for all group comparisons on raw TRD scores. Relative to the HD group, the AD group showed comparable standardized parametric TRD scores (despite lower raw nonparametric and parametric TRD scores), whereas the previous CVLT literature has shown that standardized TRD scores are lower in AD than in HD. Possible explanations for the similarity in standardized parametric TRD scores in the HD and AD groups in the present study are discussed, with an emphasis on the importance of evaluating TRD scores in the context of other indices such as FP rates in an effort to fully capture recognition memory function using the CVLT-II.

  7. Plasma homovanillic acid and prolactin in Huntington's disease.

    Science.gov (United States)

    Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

    2009-05-01

    Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). Patients were evaluated using the Unified HD Rating Scale and the Total Functional Capacity Scale. Presence of dementia, depression, and psychotic features were also assessed. The age range of the patients was 22-83 years, duration of illness from 0.5 to 27 years, and CAG repeat number from 34 to 66. A group of 60 age and sex matched healthy subjects served as control group. Plasma PRL in subjects at risk and in neuroleptic-free patients, evaluated separately for males and females, did not differ from controls. Plasma HVA levels did not differ from controls in the group of presymptomatic subjects, but were significantly higher in the patients group. This increase was positively associated mainly with severity of illness and functional capacity of the patients, and not with presence of depression or dementia. Plasma HVA levels may be proven to be a peripheral index of disease progression. Reducing dopaminergic activity may have not only symptomatic, but also neuroprotective effects in HD.

  8. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

  9. Map showing selected surface-water data for the Huntington 30 x 60-minute quadrangle, Utah

    Science.gov (United States)

    Price, Don

    1984-01-01

    This is one of a series of maps that describe the geology and related natural resources of the Huntington 30 x 60-minute quadrangle, Utah. Streamflow records used to compile this map were collected by the U.S. Geological Survey in cooperation with the Utah Department of Natural Resources, Division of Water Rights, and the Utah Department of Transportation. The principal runoff-producing area shown on the map was delineated from a work map (scale 1:250,000) compiled to estimate water yields in Utah (Bagley and others, 1964). Sources of information about recorded floods resulting from cloudbursts included Woolley (1946) and Butler and Marsell (1972); sources of information about the chemical quality of streamflow included Mundorff (1972) and Mundorff and Thompson (1982).

  10. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

    Directory of Open Access Journals (Sweden)

    Dorra Hmida-Ben Brahim

    2014-01-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

  11. Aerial gamma ray and magnetic survey, Huntington quadrangle: Ohio, West Virginia and Kentucky. Final report

    International Nuclear Information System (INIS)

    1981-04-01

    The Huntington quadrangle of Kentucky, Ohio, and West Virginia covers 7250 square miles of the easternmost Midwestern Physiographic Province. Paleozoic exposures dominate the surface. These Paleozoics deepen toward the east from approximately 500 feet to a maximum depth of 8000 feet. Precambrian basement is thought to underlie the entire area. No known uranium deposits exist in the area. One hundred anomalies were found using the standard statistical analysis. Some high uranium concentration anomalies that may overlie the stratigraphic equivalent of the Devonian-Mississippian New Albany or Chattanooga Shales may represent significant levels of naturally occurring uranium. Future studies should concentrate on this unit. Magnetic data are largely in concurrence with existing structural interpretations but suggest some complexities in the underlying Precambrian

  12. Understandings of psychological difficulties in people with the Huntington's disease gene and their expectations of psychological therapy.

    Science.gov (United States)

    Theed, Rachael; Eccles, Fiona J R; Simpson, Jane

    2018-06-01

    This study sought to investigate how people who had tested positive for the Huntington's disease (HD) gene mutation understood and experienced psychological distress and their expectations of psychological therapy. A qualitative methodology was adopted involving semi-structured interviews and interpretative phenomenological analysis (IPA). A total of nine participants (five women and four men) who had opted to engage in psychological therapy were recruited and interviewed prior to the start of this particular psychological therapeutic intervention. Interviews were transcribed verbatim and analysed using IPA whereby themes were analysed within and across transcripts and classified into superordinate themes. Three superordinate themes were developed: Attributing psychological distress to HD: 'you're blaming everything on that now'; Changes in attributions of distress over time: 'in the past you'd just get on with it'; and Approaching therapy with an open mind, commitment, and hope: 'a light at the end of the tunnel'. Understandings of psychological distress in HD included biological and psychological explanations, with both often being accepted simultaneously by the same individual but with biomedical accounts generally dominating. Individual experience seemed to reflect a dynamic process whereby people's understanding and experience of their distress changed over time. Psychological therapy was accepted as a positive alternative to medication, providing people with HD with hope that their psychological well-being could be enhanced. People with the Huntington's disease gene mutation have largely biomedical understandings of their psychological distress. This largely biomedical understanding does not, however, preclude them for being interested in the potential gains resulting from psychological therapy. The mechanisms of psychological therapy should be explained in detail before therapy and explored along with current attributions of distress. © 2017 The British

  13. Revelation of the IFN alpha, IL-10, IL-8 and IL-1 beta as promising biomarkers reflecting immuno-pathological mechanisms in porcine Huntington's disease model

    Czech Academy of Sciences Publication Activity Database

    Valeková, Ivona; Jarkovská, Karla; Kotrčová, Eva; Bucci, J.; Ellederová, Zdeňka; Juhás, Štefan; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2016-01-01

    Roč. 293, č. 2 (2016), s. 71-81 ISSN 0165-5728 R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : porcine Huntington´s disease * immune response * cytokines * central nervous system * serum * biomarkers Subject RIV: FH - Neurology Impact factor: 2.720, year: 2016

  14. Detection of early behavioral markers of Huntington's disease in R6/2 mice employing an automated social home cage

    DEFF Research Database (Denmark)

    Rudenko, Olga; Tkach, Vadim; Berezin, Vladimir

    2009-01-01

    developed behavior screening system, the IntelliCage, allows automated testing of mouse behavior in the home cage employing individual recognition of animals living in social groups. The present study validates the ability of the IntelliCage system to detect behavioral and cognitive dysfunction in R6/2 mice......Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder, for which no known cure or effective treatment exists. To facilitate the search for new potential treatments of HD, an automated system for analyzing the behavior of transgenic HD mice is urgently needed. A recently...

  15. Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

    Science.gov (United States)

    van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

    2018-04-01

    On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

  16. IV access in dental practice.

    LENUS (Irish Health Repository)

    Fitzpatrick, J J

    2009-04-01

    Intravenous (IV) access is a valuable skill for dental practitioners in emergency situations and in IV sedation. However, many people feel some apprehension about performing this procedure. This article explains the basic principles behind IV access, and the relevant anatomy and physiology, as well as giving a step-by-step guide to placing an IV cannula.

  17. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.

    Science.gov (United States)

    Díaz-Alonso, Javier; Paraíso-Luna, Juan; Navarrete, Carmen; Del Río, Carmen; Cantarero, Irene; Palomares, Belén; Aguareles, José; Fernández-Ruiz, Javier; Bellido, María Luz; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Galve-Roperh, Ismael; Muñoz, Eduardo

    2016-07-19

    Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington's-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington's disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.

  18. Complexation of the An(IV) by NTA; Complexation des An(IV) par le NTA

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, L. [Paris-11 Univ., 91 - Orsay (France)]|[CEA Valrho, Lab. de Chimie des Actinides (LCA), 30 - Marcoule (France)

    2006-07-01

    In the framework of the Nuclear and Environmental Toxicology program, developed in France, it has been decided to take again the studies concerning the actinides decorporation. A similar study of the neptunium complexation by the citrate ions has been carried out on the complexation of Np(IV) with the nitrilotriacetic acid (NTA). The NTA can be considered as a model molecule of the de-corporating molecules (amino-carboxy- ligand). The results of the spectrophotometric measurements being encouraging, the behaviour of several actinides at the same oxidation state (+IV) (Th(IV), U(IV), Np(IV), and Pu(IV)) has been determined. The experimental results are presented. In order to determine the structure of the complexes of stoichiometry 1:2 An(IV)-(NTA){sub 2} in solution, quantic chemistry calculations and EXAFS measurements have been carried out in parallel. These studies confirm the presence of An(IV)-nitrogen bonds whose length decreases from thorium to plutonium and indicate the presence of a water molecule bound to the thorium and the uranium (coordination number 8 for Np/Pu, 9 for Th/U). The evolution of the complexation constants determined in this study in terms of 1/r (r ionic radius of the cation taking into account its coordination number 8 or 9) confirms the change of the coordination number between Th/U and Np/Pu. (O.M.)

  19. Embodied emotion impairment in Huntington's Disease.

    Science.gov (United States)

    Trinkler, Iris; Devignevielle, Sévérine; Achaibou, Amal; Ligneul, Romain V; Brugières, Pierre; Cleret de Langavant, Laurent; De Gelder, Beatrice; Scahill, Rachael; Schwartz, Sophie; Bachoud-Lévi, Anne-Catherine

    2017-07-01

    Theories of embodied cognition suggest that perceiving an emotion involves somatovisceral and motoric re-experiencing. Here we suggest taking such an embodied stance when looking at emotion processing deficits in patients with Huntington's Disease (HD), a neurodegenerative motor disorder. The literature on these patients' emotion recognition deficit has recently been enriched by some reports of impaired emotion expression. The goal of the study was to find out if expression deficits might be linked to a more motoric level of impairment. We used electromyography (EMG) to compare voluntary emotion expression from words to emotion imitation from static face images, and spontaneous emotion mimicry in 28 HD patients and 24 matched controls. For the latter two imitation conditions, an underlying emotion understanding is not imperative (even though performance might be helped by it). EMG measures were compared to emotion recognition and to the capacity to identify and describe emotions using alexithymia questionnaires. Alexithymia questionnaires tap into the more somato-visceral or interoceptive aspects of emotion perception. Furthermore, we correlated patients' expression and recognition scores to cerebral grey matter volume using voxel-based morphometry (VBM). EMG results replicated impaired voluntary emotion expression in HD. Critically, voluntary imitation and spontaneous mimicry were equally impaired and correlated with impaired recognition. By contrast, alexithymia scores were normal, suggesting that emotion representations on the level of internal experience might be spared. Recognition correlated with brain volume in the caudate as well as in areas previously associated with shared action representations, namely somatosensory, posterior parietal, posterior superior temporal sulcus (pSTS) and subcentral sulcus. Together, these findings indicate that in these patients emotion deficits might be tied to the "motoric level" of emotion expression. Such a double

  20. Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

    Science.gov (United States)

    Djoussé, Luc; Knowlton, Beth; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R.; Ross, Christopher A.; Margolis, Russel L.; Rosenblatt, Adam; Durr, Alexandra; Dode, Catherine; Morrison, Patrick J.; Novelletto, Andrea; Frontali, Marina; Trent, Ronald J. A.; McCusker, Elizabeth; Gómez-Tortosa, Estrella; Mayo Cabrero, David; Jones, Randi; Zanko, Andrea; Nance, Martha; Abramson, Ruth K.; Suchowersky, Oksana; Paulsen, Jane S.; Harrison, Madaline B.; Yang, Qiong; Cupples, L. Adrienne; Mysore, Jayalakshmi; Gusella, James F.; MacDonald, Marcy E.

    2007-01-01

    Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Δ2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Δ2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker. PMID:15029481

  1. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington's disease.

    Science.gov (United States)

    Valenza, M; Marullo, M; Di Paolo, E; Cesana, E; Zuccato, C; Biella, G; Cattaneo, E

    2015-04-01

    In the adult brain, neurons require local cholesterol production, which is supplied by astrocytes through apoE-containing lipoproteins. In Huntington's disease (HD), such cholesterol biosynthesis in the brain is severely reduced. Here we show that this defect, occurring in astrocytes, is detrimental for HD neurons. Astrocytes bearing the huntingtin protein containing increasing CAG repeats secreted less apoE-lipoprotein-bound cholesterol in the medium. Conditioned media from HD astrocytes and lipoprotein-depleted conditioned media from wild-type (wt) astrocytes were equally detrimental in a neurite outgrowth assay and did not support synaptic activity in HD neurons, compared with conditions of cholesterol supplementation or conditioned media from wt astrocytes. Molecular perturbation of cholesterol biosynthesis and efflux in astrocytes caused similarly altered astrocyte-neuron cross talk, whereas enhancement of glial SREBP2 and ABCA1 function reversed the aspects of neuronal dysfunction in HD. These findings indicate that astrocyte-mediated cholesterol homeostasis could be a potential therapeutic target to ameliorate neuronal dysfunction in HD.

  2. D-β-hydroxybutyrate is protective in mouse models of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Soyeon Lim

    Full Text Available Abnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental in Huntington's disease (HD, a fatal genetic disorder caused by an expanded polyglutamine track in the protein huntingtin. Given the lack of effective therapies for HD, we sought to assess the neuroprotective properties of the mitochondrial energizing ketone body, D-β-hydroxybutyrate (DβHB, in the 3-nitropropionic acid (3-NP toxic and the R6/2 genetic model of HD. In mice treated with 3-NP, a complex II inhibitor, infusion of DβHB attenuates motor deficits, striatal lesions, and microgliosis in this model of toxin induced-striatal neurodegeneration. In transgenic R6/2 mice, infusion of DβHB extends life span, attenuates motor deficits, and prevents striatal histone deacetylation. In PC12 cells with inducible expression of mutant huntingtin protein, we further demonstrate that DβHB prevents histone deacetylation via a mechanism independent of its mitochondrial effects and independent of histone deacetylase inhibition. These pre-clinical findings suggest that by simultaneously targeting the mitochondrial and the epigenetic abnormalities associated with mutant huntingtin, DβHB may be a valuable therapeutic agent for HD.

  3. Diffusion tensor imaging of brain white matter in Huntington gene mutation individuals

    Directory of Open Access Journals (Sweden)

    Roberta Arb Saba

    Full Text Available ABSTRACT Objective To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease. Methods We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls. We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy. Results We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups. Conclusion White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.

  4. PPARGC1A/PGC-1α, TFEB and enhanced proteostasis in Huntington disease: Defining regulatory linkages between energy production and protein–organelle quality control

    OpenAIRE

    La Spada, Albert R.

    2012-01-01

    Huntington disease (HD) results from CAG repeats that encode expanded polyglutamine tracts in the HTT/huntingtin protein. HD belongs to a large category of inherited and sporadic neurodegenerative disorders in which production of a misfolded protein initiates the pathogenic cascade. Previous studies have shown that misfolded proteins become resistant to cellular protein turnover pathways by eluding and disabling the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway. Based upon ...

  5. Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

    Science.gov (United States)

    Hansen, Ryan N; Pham, An T; Lovelace, Belinda; Balaban, Stela; Wan, George J

    2017-10-01

    Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

  6. Age at onset in Huntington's disease: replication study on the association of HAP1.

    Science.gov (United States)

    Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

    2012-11-01

    In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

  7. X-Band Electron Paramagnetic Resonance Comparison of Mononuclear Mn(IV)-oxo and Mn(IV)-hydroxo Complexes and Quantum Chemical Investigation of Mn(IV) Zero-Field Splitting.

    Science.gov (United States)

    Leto, Domenick F; Massie, Allyssa A; Colmer, Hannah E; Jackson, Timothy A

    2016-04-04

    X-band electron paramagnetic resonance (EPR) spectroscopy was used to probe the ground-state electronic structures of mononuclear Mn(IV) complexes [Mn(IV)(OH)2(Me2EBC)](2+) and [Mn(IV)(O)(OH)(Me2EBC)](+). These compounds are known to effect C-H bond oxidation reactions by a hydrogen-atom transfer mechanism. They provide an ideal system for comparing Mn(IV)-hydroxo versus Mn(IV)-oxo motifs, as they differ by only a proton. Simulations of 5 K EPR data, along with analysis of variable-temperature EPR signal intensities, allowed for the estimation of ground-state zero-field splitting (ZFS) and (55)Mn hyperfine parameters for both complexes. From this analysis, it was concluded that the Mn(IV)-oxo complex [Mn(IV)(O)(OH)(Me2EBC)](+) has an axial ZFS parameter D (D = +1.2(0.4) cm(-1)) and rhombicity (E/D = 0.22(1)) perturbed relative to the Mn(IV)-hydroxo analogue [Mn(IV)(OH)2(Me2EBC)](2+) (|D| = 0.75(0.25) cm(-1); E/D = 0.15(2)), although the complexes have similar (55)Mn values (a = 7.7 and 7.5 mT, respectively). The ZFS parameters for [Mn(IV)(OH)2(Me2EBC)](2+) were compared with values obtained previously through variable-temperature, variable-field magnetic circular dichroism (VTVH MCD) experiments. While the VTVH MCD analysis can provide a reasonable estimate of the magnitude of D, the E/D values were poorly defined. Using the ZFS parameters reported for these complexes and five other mononuclear Mn(IV) complexes, we employed coupled-perturbed density functional theory (CP-DFT) and complete active space self-consistent field (CASSCF) calculations with second-order n-electron valence-state perturbation theory (NEVPT2) correction, to compare the ability of these two quantum chemical methods for reproducing experimental ZFS parameters for Mn(IV) centers. The CP-DFT approach was found to provide reasonably acceptable values for D, whereas the CASSCF/NEVPT2 method fared worse, considerably overestimating the magnitude of D in several cases. Both methods were poor in

  8. IV treatment at home

    Science.gov (United States)

    ... Other IV treatments you may receive after you leave the hospital include: Treatment for hormone deficiencies Medicines for severe nausea that cancer chemotherapy or pregnancy may cause Patient-controlled analgesia (PCA) for pain (this is IV ...

  9. Bradykinesia in Huntington's disease. A prospective, follow-up study.

    Science.gov (United States)

    García Ruiz, Pedro J; Hernández, Jaime; Cantarero, Susana; Bartolomé, Manuel; Sánchez Bernardos, Vicenta; García de Yébenez, Justo

    2002-04-01

    Bradykinesia is a frequent finding in Huntington's disease (HD), but some aspects are presently unknown; including the natural evolution of bradykinesia over time and the correlation between bradykinesia and functional capacity. We studied the motor performance of 20 genetically confirmed patients with HD (age: 40+/-10.8 years; age at onset 33.6+/-11 years; total functional capacity (TFC): 9.57+/-3; UHDRS total motor scale: 31.4+/-13, triplet length (CAG)n: 46.7+/-4 triplets). These patients were studied in baseline conditions and after 18.7+/-6 months of follow-up. In addition, HD patients were compared with 20 age-matched normal controls. Motor study included the four CAPIT timed tests commonly used for Parkinson's disease: pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). HD patients were significantly slower than controls in all motor tasks. A significant deterioration occurred over time in three of the four motor tasks (especially FD and WT). A significant correlation between timed tests and TFC score was found (for MTP, r: -0.845; p < 0,0001). In addition a significant correlation between timed tests and the UHDRDS total motor scale was also found (for MTP, r: 0.864; p < 0.0001). In conclusion, simple timed motor tests can detect a deterioration of motor activity over time in HD. Timed tests might be useful to follow the natural evolution of HD and to assess the efficacy of new therapies.

  10. Therapeutic approaches to preventing cell death in Huntington disease.

    Science.gov (United States)

    Kaplan, Anna; Stockwell, Brent R

    2012-12-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. A cerium(IV)-carbon multiple bond

    Energy Technology Data Exchange (ETDEWEB)

    Gregson, Matthew; Lu, Erli; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Liddle, Stephen T. [Nottingham Univ. (United Kingdom). School of Chemistry

    2013-12-02

    Straightforward access to a cerium(IV)-carbene complex was provided by one-electron oxidation of an anionic ''ate'' cerium(III)-carbene precursor, thereby avoiding decomposition reactions that plague oxidations of neutral cerium(III) compounds. The cerium(IV)-carbene complex is the first lanthanide(IV)-element multiple bond and involves a twofold bonding interaction of two electron pairs between cerium and carbon. [German] Auf direktem Wege zu einem Cer(IV)-Carbenkomplex gelangt man durch die Einelektronenoxidation einer anionischen Carben-Cerat(III)-Vorstufe. So werden Zersetzungsprozesse vermieden, die die Oxidation neutraler Cer(III)-Verbindungen erschweren. Der Cer(IV)-Carbenkomplex enthaelt die erste Lanthanoid(IV)-Element-Mehrfachbindung; dabei binden Cer und Kohlenstoff ueber zwei Elektronenpaare.

  12. Estudio de los procesos activadores de la patologia en la enfermedad de Huntington: Alteraciones en la plasticidad sinaptica y perspectivas terapeuticas

    OpenAIRE

    Giralt Torroella, Albert

    2010-01-01

    [spa] La presente tesis posee una introducción donde se plantea y explica la sintomatología, genética y fisiopatología de la enfermedad de Huntington (EH). También explicamos los distintos modelos animales usados para el estudio de la enfermedad y resaltamos su relevancia para propuestas terapéuticas. Seguidamente introducimos lo que son las ideas principales de la tesis. Estas son, el interés por el estudio de los procesos fisiopatológicos de aparición más temprana para la planificación tera...

  13. Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates.

    Science.gov (United States)

    Nongonierma, Alice B; Paolella, Sara; Mudgil, Priti; Maqsood, Sajid; FitzGerald, Richard J

    2018-04-01

    Nine novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (FLQY, FQLGASPY, ILDKEGIDY, ILELA, LLQLEAIR, LPVP, LQALHQGQIV, MPVQA and SPVVPF) were identified in camel milk proteins hydrolysed with trypsin. This was achieved using a sequential approach combining liquid chromatography tandem mass spectrometry (LC-MS/MS), qualitative/quantitative structure activity relationship (QSAR) and confirmatory studies with synthetic peptides. The most potent camel milk protein-derived DPP-IV inhibitory peptides, LPVP and MPVQA, had DPP-IV half maximal inhibitory concentrations (IC 50 ) of 87.0 ± 3.2 and 93.3 ± 8.0 µM, respectively. DPP-IV inhibitory peptide sequences identified within camel and bovine milk protein hydrolysates generated under the same hydrolysis conditions differ. This was linked to differences in enzyme selectivity for peptide bond cleavage of camel and bovine milk proteins as well as dissimilarities in their amino acid sequences. Camel milk proteins contain novel DPP-IV inhibitory peptides which may play a role in the regulation of glycaemia in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Identification of extreme motor phenotypes in Huntington's disease.

    Science.gov (United States)

    Braisch, Ulrike; Hay, Birgit; Muche, Rainer; Rothenbacher, Dietrich; Landwehrmeyer, G Bernhard; Long, Jeffrey D; Orth, Michael

    2017-04-01

    The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Brain imaging and cognitive dysfunctions in Huntington's disease

    Science.gov (United States)

    Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

    2006-01-01

    Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

  16. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    Energy Technology Data Exchange (ETDEWEB)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

    2009-07-15

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  17. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    International Nuclear Information System (INIS)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

    2009-01-01

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  18. Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

    Science.gov (United States)

    Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

    Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study

    Directory of Open Access Journals (Sweden)

    Jane S Paulsen

    2014-04-01

    Full Text Available There is growing consensus that intervention and treatment of Huntington disease (HD should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

  20. Inactivation of the Huntington's disease gene (Hdh impairs anterior streak formation and early patterning of the mouse embryo

    Directory of Open Access Journals (Sweden)

    Conlon Ronald A

    2005-08-01

    Full Text Available Abstract Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in

  1. Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo.

    Science.gov (United States)

    Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

    2005-08-18

    Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5) huntingtin deficient embryos. In the absence of huntingtin, expression of nutritive genes appears normal but E7.0-7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

  2. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  3. Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

    Science.gov (United States)

    Cole, James H; Farmer, Ruth E; Rees, Elin M; Johnson, Hans J; Frost, Chris; Scahill, Rachael I; Hobbs, Nicola Z

    2014-03-21

    Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions.

  4. Hacia una terapia neuroprotectora con cannabinoides en la enfermedad de Huntington : estudios preclínicos y clínicos

    OpenAIRE

    Valdeolivas Rojas, Sara

    2017-01-01

    La enfermedad de Huntington (EH) es una enfermedad con herencia autosómica dominante causada por una mutación en el gen IT15, que codifica la proteína huntingtina (HTT). Esta proteína presenta una amplia expresión células de mamíferos y, aunque su función exacta no es totalmente conocida, se sabe que está relacionada con la modulación de procesos celulares tales como transcripción génica, señalización celular, metabolismo energético y neurogénesis. La mutación consiste en una expansión excesi...

  5. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    International Nuclear Information System (INIS)

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-01-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation

  6. Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

    Science.gov (United States)

    Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2017-08-08

    Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

  7. From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

    Science.gov (United States)

    Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

    2014-01-01

    Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

  8. Level II scour analysis for Bridge 30, (HUNTTH00220030), on Town Highway 22, crossing Brush Brook, Huntington, Vermont

    Science.gov (United States)

    Burns, Ronda L.

    1997-01-01

    This report provides the results of a detailed Level II analysis of scour potential at structure HUNTTH00220030 on Town Highway 22 crossing Brush Brook, Huntington, Vermont (figures 1–8). A Level II study is a basic engineering analysis of the site, including a quantitative analysis of stream stability and scour (U.S. Department of Transportation, 1993). Results of a Level I scour investigation also are included in Appendix E of this report. A Level I investigation provides a qualitative geomorphic characterization of the study site. Information on the bridge, gleaned from Vermont Agency of Transportation (VTAOT) files, was compiled prior to conducting Level I and Level II analyses and is found in Appendix D.

  9. Complexes of uranium (IV) and thorium (IV) with α-picolinic acid, nicotinic acid, anthranilic acid and N-phenylanthranilic acid

    International Nuclear Information System (INIS)

    Singh, M.; Singh, R.

    1979-01-01

    Stable U(IV) and Th(IV) complexes with the title ligands have been synthesised from U(OAc) 4 , and Th(OAc) 4 . Magnetic susceptibilities, IR and reflectance spectra of U(IV) and IR spectra of Th(IV) complexes have been studied which indicate eight coordination for U(IV) in these chelates. (auth.)

  10. Thorium(IV) and zirconium(IV) complexes of oxygen donor ligands. Pt. 12

    International Nuclear Information System (INIS)

    Agarwal, R.K.; Jain, P.C.; Kapur, V.; Sharma, S.; Srivastava, A.K.

    1980-01-01

    Crystalline thorium (IV) chelates with mono N-oxides of 2,2'-bipyridine (bipyNO) and 1,10-phenanthroline (phenNO), ThX 4 x 2L(X = Cl,Br,NO 3 or NCS) and ThX 4 x 3L(X = I or ClO 4 and L = bipyNO or phenNO) have been synthesised and characterized on the basis of i.r. spectra, molar conductance, molecular weights, t.g.a. and d.t.a. data. All the complexes are weakly diamagnetic and contain bipyNO and phenNO bonded to thorium(IV) through nitrogen and oxygen. The coordination number of thorium(IV) varies from six to twelve depending on the nature of the anions. (orig.) [de

  11. Solubility of Tc(IV) oxides

    International Nuclear Information System (INIS)

    Liu, D.J.; Fan, X.H.

    2005-01-01

    Full text of publication follows: The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 .nH 2 O. The solubility of Tc(IV) is used as a source term in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2+ . The solubility of Tc(IV) oxide has been determined in simulated groundwater and re-distilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and re-distilled water is about (1.49∼1.86) x 10 -9 mol/(L.d) under aerobic conditions, but Tc(IV) in simulated groundwater and re-distilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and re-distilled water is equal on the whole after centrifugation or ultrafiltration. The solubility of Tc(IV) oxide decreases with the increase of pH at pH 10 and is pH independent in the range 2 -8 to 10 -9 mol/L at 2 3 2- concentration. These data could be used to estimate the Tc(IV) solubility for cases where solubility limits transport of technetium in reducing environments of high-level waste repositories. (authors)

  12. Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.

    Science.gov (United States)

    Xiao, Yucheng; Jackson, James O; Liang, Songping; Cummins, Theodore R

    2011-08-05

    The voltage sensors of domains II and IV of sodium channels are important determinants of activation and inactivation, respectively. Animal toxins that alter electrophysiological excitability of muscles and neurons often modify sodium channel activation by selectively interacting with domain II and inactivation by selectively interacting with domain IV. This suggests that there may be substantial differences between the toxin-binding sites in these two important domains. Here we explore the ability of the tarantula huwentoxin-IV (HWTX-IV) to inhibit the activity of the domain II and IV voltage sensors. HWTX-IV is specific for domain II, and we identify five residues in the S1-S2 (Glu-753) and S3-S4 (Glu-811, Leu-814, Asp-816, and Glu-818) regions of domain II that are crucial for inhibition of activation by HWTX-IV. These data indicate that a single residue in the S3-S4 linker (Glu-818 in hNav1.7) is crucial for allowing HWTX-IV to interact with the other key residues and trap the voltage sensor in the closed configuration. Mutagenesis analysis indicates that the five corresponding residues in domain IV are all critical for endowing HWTX-IV with the ability to inhibit fast inactivation. Our data suggest that the toxin-binding motif in domain II is conserved in domain IV. Increasing our understanding of the molecular determinants of toxin interactions with voltage-gated sodium channels may permit development of enhanced isoform-specific voltage-gating modifiers.

  13. On the stabilization of niobium(V) solutions by zirconium(IV) and hafnium(IV)

    DEFF Research Database (Denmark)

    Sørensen, E.; Bjerre, A.B.

    1992-01-01

    Niobium cannot be separated from zirconium or hafnium when these elements occur together in solution with common anions such as chloride and sulphate. This is ascribed to the co-polymerization of niobium(V) and the hydrolysed ionic species of zirconium(IV) and hafnium(IV) to form colloidal...

  14. Neptunium (IV) oxalate solubility

    International Nuclear Information System (INIS)

    Luerkens, D.W.

    1983-07-01

    The equilibrium solubility of neptunium (IV) oxalate in nitric/oxalic acid solutions was determined at 22 0 C, 45 0 C, and 60 0 C. The concentrations of nitric/oxalic acid solutions represented a wide range of free oxalate ion concentration. A mathematical solubility model was developed which is based on the formation of the known complexes of neptunium (IV) oxalate. the solubility model uses a simplified concentration parameter which is proportional to the free oxalate ion concentration. The solubility model can be used to estimate the equilibrium solubility of neptunium (IV) oxalate over a wide range of oxalic and nitric acid concentrations at each temperature

  15. Enhanced Design Alternative IV

    International Nuclear Information System (INIS)

    Kramer, N.E.

    1999-01-01

    This report evaluates Enhanced Design Alternative (EDA) IV as part of the second phase of the License Application Design Selection (LADS) effort. The EDA IV concept was compared to the VA reference design using criteria from the Design Input Request for LADS Phase II EDA Evaluations (CRWMS M and O 1999b) and (CRWMS M and O 1999f). Briefly, the EDA IV concept arranges the waste packages close together in an emplacement configuration known as line load. Continuous pre-closure ventilation keeps the waste packages from exceeding their 350 C cladding and 200 C (4.3.6) drift wall temperature limits. This EDA concept keeps relatively high, uniform emplacement drift temperatures (post-closure) to drive water away from the repository and thus dry out the pillars between emplacement drifts. The waste package is shielded to permit human access to emplacement drifts and includes an integral filler inside the package to reduce the amount of water that can contact the waste form. Closure of the repository is desired 50 years after first waste is emplaced. Both backfill and drip shields will be emplaced at closure to improve post-closure performance. The EDA IV concept includes more defense-in-depth layers than the VA reference design because of its backfill, drip shield, waste package shielding, and integral filler features. These features contribute to the low dose-rate to the public achieved during the first 10,000 years of repository life as shown in Figure 3. Investigation of the EDA IV concept has led to the following general conclusions: (1) The total life cycle cost for EDA IV is about $21.7 billion which equates to a $11.3 billion net present value (both figures rounded up). (2) The incidence of design basis events for EDA IV is similar to the VA reference design. (3) The emplacement of the waste packages in drifts will be similar to the VA reference design. However, heavier equipment may be required because the shielded waste package will be heavier. (4) The heavier

  16. Synthesis and characterization of thorium(IV) and uranium(IV) complexes with Schiff bases

    Energy Technology Data Exchange (ETDEWEB)

    Radoske, Thomas; Maerz, Juliane; Kaden, Peter; Patzschke, Michael; Ikeda-Ohno, Atsushi [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Chemistry of the F-Elements

    2017-06-01

    We report herein the synthesis and characterization of several imine complexes of tetravalent thorium (Th(IV)) and uranium (U(IV)). The ligands investigated in this study are a Schiff base type, including the well-known salen ligand (H{sub 2}Le, Fig. 1). The complexation in solution was investigated by NMR measurements indicating paramagnetic effects of unpaired f-electrons of U(IV) on the ligand molecule. We also determined the solid-state molecular structures of the synthesized complexes by single crystal X-ray diffraction. The synthesized complexes show an eight-fold coordination geometry around the actinide center surrounded by two tetradentate ligands with 2N- and 2O-donor atoms.

  17. Late-onset Huntington's disease: diagnostic and prognostic considerations.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

    2014-07-01

    To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). We analyzed a cohort of 41 late-onset (≥60 years) HD patients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HD patients. Disease severity was assessed by the Total Functional Capacity Scale. Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HD patients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HD patients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a severe stage of illness on average 2.8 years earlier than usual-onset HD patients (p = 0.046). A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. 77 FR 2096 - Notice of Availability of Draft Environmental Impact Statement for the Proposed International...

    Science.gov (United States)

    2012-01-13

    ... Center, 5101 Lovington Highway in Hobbs, New Mexico. For 1 hour prior to the public meeting, the NRC..., 5101 Lovington Highway in Hobbs, New Mexico. Informal Open House Session: 4:30-5:30 p.m. Draft EIS...

  19. The kinetics of the cerium(IV)-uranium(IV) reaction at low sulfate concentrations

    International Nuclear Information System (INIS)

    Michaille, P.; Kikindai, T.

    1977-01-01

    The rate of oxidation of uranium(IV) by cerium(IV) was measured with a stopped-flow spectrophotometer at sulfuric acid concentrations of 2 x 10 -6 to 0.5 M. At a constant hydrogen ion concentration of 0.5 M, the maximum rate constant was observed for 2 x 10 -3 M sulfuric acid; at that concentration, two sulfate ions were involved in the activated complex. The dependence of the rate constant on the hydrogen ion concentration showed that the reaction paths involving one or two sulfate ions also involved one hydroxyl ion, whereas one hydrogen ion was involved in the five sulfate dependent path. Spectrophotometric measurements supported the existence of a hydrolyzed monosulfatocomplex of cerium(IV). (author)

  20. Sleep-related modifications of EEG connectivity in the sensory-motor networks in Huntington Disease: An eLORETA study and review of the literature.

    Science.gov (United States)

    Piano, Carla; Imperatori, Claudio; Losurdo, Anna; Bentivoglio, Anna Rita; Cortelli, Pietro; Della Marca, Giacomo

    2017-07-01

    To evaluate EEG functional connectivity in the sensory-motor network, during wake and sleep, in patients with Huntington Disease (HD). 23 patients with HD and 23 age- and sex-matched healthy controls were enrolled. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA). In wake, HD patients showed an increase of delta lagged phase synchronization (T=3.60; p<0.05) among Broadman's Areas (BA) 6-8 bilaterally; right BA 6-8 and right BA 1-2-3; left BA 1-2-3 and left BA 4. In NREM, HD patients showed an increase of delta lagged phase synchronization (T=3.56; p<0.05) among left BA 1-2-3 and right BA 6-8. In REM, HD patients showed an increase of lagged phase synchronization (T=3.60; p<0.05) among the BA 6-8 bilaterally (delta band); left BA 1-2-3 and right BA 1-2-3 (theta); left BA 1-2-3 and right BA 4 (theta); left BA 1-2-3 and right BA 1-2-3 (alpha). Our results may reflect an abnormal function of the motor areas or an effort to counterbalance the pathological motor output. Our results may help to understand the pathophysiology of sleep-related movement disorders in Huntington's Disease, and to define therapeutically strategies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  1. Diorganotin(IV) Complexes with Methionine Methyl Ester. Equilibria ...

    African Journals Online (AJOL)

    IV) (DBT) and diphenyltin(IV) (DPT) was investigated at 25 °C and 0.1 mol dm–3 ionic strength in water for dimethyltin(IV) and in 50 % dioxane–water mixture for dibutyltin(IV) and diphenyltin(IV). Methionine methyl ester forms1:1 and 1:2 ...

  2. Adsorption of Th(IV) and Pu(IV) on the surface of Pseudomonas fluorescens and Bacillus subtilis in the presence of desferrioxamine siderophore

    International Nuclear Information System (INIS)

    Yoshida, Takahiro; Ozaki, Takuo; Ohnuki, Toshihiko; Francis, Arokiasamy J.

    2005-01-01

    Adsorption of Th(IV) and Pu(IV) on a Gram-negative bacterium Pseudomonas fluorescens and a Gram-positive bacterium Bacillus subtilis in the presence of siderophore desferrioxamine B (DFO) was studied. Thorium(IV) and Pu(IV) were dissociated from DFO during adsorption on the cells. Thorium(IV) adsorption on bacterial cells in the presence of DFO was larger than that of Pu(IV) because of the smaller stability of the Th(IV)-DFO complex than that of the Pu(IV)-DFO complex. On the other hand, adsorption of Pu(IV) was larger than that of Fe(III), wherein the stability of the Pu(IV)- and Fe(III)-DFO complex is comparable. P. fluorescens showed a higher affinity for Th(IV) and Pu(IV) than B. subtilis, though potentiometric titration of bacterial cells indicated that surfaces of P. fluorescens and B. subtilis cells showed similar proton binding properties. (author)

  3. Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.

    Science.gov (United States)

    Jędrak, Paulina; Krygier, Magdalena; Tońska, Katarzyna; Drozd, Małgorzata; Kaliszewska, Magdalena; Bartnik, Ewa; Sołtan, Witold; Sitek, Emilia J; Stanisławska-Sachadyn, Anna; Limon, Janusz; Sławek, Jarosław; Węgrzyn, Grzegorz; Barańska, Sylwia

    2017-08-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels. Although the type of mitochondrial haplogroup had no influence on the mtDNA level, and there was no correlation between mtDNA level in leukocytes in HD patients and various parameters of HD severity, some considerable differences between HD patients and controls were identified. The average mtDNA/nDNA relative copy number was significantly higher in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes than HD men. Because this is the largest population analysed to date, these results might contribute to explanation of discrepancies between previously published studies concerning levels of mtDNA in cells of HD patients. We suggest that the size of the investigated population and type of cells from which DNA is isolated could significantly affect results of mtDNA copy number estimation in HD. Hence, these parameters should be taken into consideration in studies on mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction occurs.

  4. Pitfalls in the detection of cholesterol in Huntington's disease models.

    Science.gov (United States)

    Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

    2012-10-11

    Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

  5. Predictive gene testing for Huntington disease and other neurodegenerative disorders.

    Science.gov (United States)

    Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

    2013-12-01

    Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  6. A combined XAFS, ESI TOF-MS and LIBD study on the formation of polynuclear Zr(IV), Th(IV) and Pu(IV) species

    Science.gov (United States)

    Rothe, J.; Walther, C.; Brendebach, B.; Büchner, S.; Fuss, M.; Denecke, M. A.; Geckeis, H.

    2009-11-01

    The long term radiotoxicity of spent nuclear fuel disposed of in deep underground repositories after discharge from nuclear power reactors is determined by actinide elements, mainly plutonium. Water intrusion into the repository might cause container corrosion and leaching of the waste matrices, leading to the release of Pu and other actinides into the geological environment. Performance assessment for a future nuclear waste repository requires detailed knowledge on actinide aqueous chemistry in the aquifer surrounding the disposal site. Tetravalent actinides exhibit a strong tendency towards hydrolysis and subsequent polymerization and/or colloid formation. These species provide a potential pathway for migration of actinides away from the repository. Therefore, it is of fundamental interest to study their generation and properties in-situ. To this end, X-ray Absorption Fine Structure Spectroscopy (XAFS) at the INE-Beamline for actinide research at ANKA, Electrospray Mass-Spectrometry (ESI TOF-MS) and Laser Induced Breakdown Detection (LIBD) are combined at FZK-INE in a comprehensive attempt to characterize Zr(IV) (An(IV) analogue), Th(IV) and Pu(IV) polymerization and colloid formation.

  7. Poder, autoridade e tradição

    Directory of Open Access Journals (Sweden)

    José N. Heck

    2007-06-01

    Full Text Available The article starts focusing on Hobbes' absolutism under the scope of the traditional doctrine of natural right. Then exposes the complex relation between Hobbes and democracy and his notion of political representation. After reconstructing some of Hobbes' basic objections to classical political thought, the text tries to show that the English philosopher works, with respect to Aristotle, with a relatively unaltered concept of nature. The major objective of the paper is to configure the State as a genuine product of the intellectual performance of the English political theoretician.

  8. Generation IV national program

    International Nuclear Information System (INIS)

    Preville, M.; Sadhankar, R.; Brady, D.

    2007-01-01

    This paper outlines the Generation IV National Program. This program involves evolutionary and innovative design with significantly higher efficiencies (∼50% compared to present ∼30%) - sustainable, economical, safe, reliable and proliferation resistant - for future energy security. The Generation IV Forum (GIF) effectively leverages the resources of the participants to meet these goals. Ten countries signed the GIF Charter in 2001

  9. Solubility studies of Np(IV)

    International Nuclear Information System (INIS)

    Zhang Yingjie; Yao Jun; Jiao Haiyang; Ren Lihong; Zhou Duo; Fan Xianhua

    2001-01-01

    The solubility of Np(IV) in simulated underground water and redistilled water has been measured with the variations of pH(6-12) and storage time (0-100 d) in the presence of reductant (Na 2 S 2 O 4 , metallic Fe). All experiments are performed in a low oxygen concentration glove box containing high purity Ar(99.99%), with an oxygen content of less than 5 x 10 -6 mol/mol. Experimental results show that the variation of pH in solution has little effect on the solubility of Np(IV) in the two kinds of water; the measured solubility of Np(IV) is affected by the composition of solution; with Na 2 S 2 O 4 as a reductant, the solubility of Np(IV) in simulated underground water is (9.23 +- 0.48) x 10 -10 mol/L, and that in redistilled water is (8.31 +- 0.35) x 10 -10 mol/L; with metallic Fe as a reductant, the solubility of Np(IV) in simulated underground water is (1.85 +- 0.56) x 10 -9 mol/L, and that in redistilled water is (1.48 +- 0.66) x 10 -9 mol/L

  10. Materials for generation-IV nuclear reactors

    International Nuclear Information System (INIS)

    Alvarez, M. G.

    2009-01-01

    Materials science and materials development are key issues for the implementation of innovative reactor systems such as those defined in the framework of the Generation IV. Six systems have been selected for Generation IV consideration: gas-cooled fast reactor, lead-cooled fast reactor, molten salt-cooled reactor, sodium-cooled fast reactor, supercritical water-cooled reactor, and very high temperature reactor. The structural materials need to resist much higher temperatures, higher neutron doses and extremely corrosive environment, which are beyond the experience of the current nuclear power plants. For this reason, the first consideration in the development of Generation-IV concepts is selection and deployment of materials that operate successfully in the aggressive operating environments expected in the Gen-IV concepts. This paper summarizes the Gen-IV operating environments and describes the various candidate materials under consideration for use in different structural applications. (author)

  11. Adduct formation in Ce(IV) thenolytrifluoroacetonate

    International Nuclear Information System (INIS)

    Anufrieva, S.I.; Polyakova, G.V.; Snezhko, N.I.; Pechurova, N.I.; Martynenko, L.I.; Spitsyn, V.I.

    1982-01-01

    The literature contains no information on adduct formation in Ce(IV) β-diketonates with additional ligands. Since tetrakis-β-diketonates of Ce(IV) have four six-membered chelate rings, we can suppose that the introduction of an additional monodentate or bidentate ligand into the coordination sphere of Ce(IV) β-diketonates would lead to an increase in the coordination number (CN) of the Ce(IV) to nine or ten. The possibility of realization of such a high CN for Ce(IV) has not been proved; a study of adduct formation by Ce(IV) tetrakis-β-diketonates is thus of theoretical interest. Such an investigation might also be of practical interest, because the introduction of an additional ligand into the coordination sphere of a rare-earth β-diketonate usually increases the solubility of the β-diketonate in nonpolar solvents and increases the volatility of the compound; such a modification of the properties is important for various practical purposes. The aim of our work was to study the possibility of separating solid adducts of Ce(IV) tetrakis-thenoyltrifluoroacetonate with certain oxygen-containing and nitrogen-containing donor monodentate and bidentate ligands, and also to investigate their properties. As the β-diketone we used thenoyltrifluoroacetone (HTTFA), since in a parallel investigation it was found that Ce(TTFA) 4 has a high oxidation-reduction stability

  12. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  13. Epidemiological Study of Huntington's Disease in the Province of Ferrara, Italy.

    Science.gov (United States)

    Carrassi, Erika; Pugliatti, Maura; Govoni, Vittorio; Sensi, Mariachiara; Casetta, Ilaria; Granieri, Enrico

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of CAG triplet repeat. We aimed to reappraise HD epidemiology in a northern Italian population, in relation to introduction of genetic testing. Through ICD-9M code 333.4 and medical fare exemption code RF0080, HD cases were identified from administrative health data and medical records from the Units of Neurology and Genetics, Ferrara University Hospital, and from other provincial neurological structures. HD mean annual incidence rate in 1990-2009 was 0.3 per 100,000 (95% CI 0.2-0.5). All incident cases were found to have symptoms of the disease's classic form, and neither juvenile nor the rigid Westphal variant was detected. The mean (SD) age at onset was 50.2 (12.7 years; range 32-82 years), 54.9 (14.6) for men and 45.8 (9.4) for women. On prevalence day, December 31, 2014, HD prevalence was 4.2 per 100,000 (95% CI 2.4-7.0), with a male:female ratio of 1:2. The prevalence and incidence of HD in our population were lower than the prevalence and incidence reported for other European and Italian populations, but higher compared to those of Asia, Africa, and Eastern Europe. Compared to previous studies, HD incidence and prevalence did not change significantly. © 2017 S. Karger AG, Basel.

  14. Genetics Home Reference: glycogen storage disease type IV

    Science.gov (United States)

    ... Home Health Conditions Glycogen storage disease type IV Glycogen storage disease type IV Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type IV (GSD IV) is an ...

  15. Patterns of False Memory in Patients with Huntington's Disease.

    Science.gov (United States)

    Chen, I-Wen; Chen, Chiung-Mei; Wu, Yih-Ru; Hua, Mau-Sun

    2017-06-01

    Increased false memory recognition in patients with Huntington's disease (HD) has been widely reported; however, the underlying memory constructive processes remain unclear. The present study explored gist memory, item-specific memory, and monitoring ability in patients with HD. Twenty-five patients (including 13 patients with mild HD and 12 patients with moderate-to-severe HD) and 30 healthy comparison participants (HC) were recruited. We used the Deese-Roediger-McDermott (DRM) paradigm to investigate participants' false recognition patterns, along with neuropsychological tests to assess general cognitive function. Both mild and moderate-to-severe patients with HD showed significant executive functioning and episodic memory impairment. On the DRM tasks, both HD patient groups showed significantly impaired performance in tasks assessing unrelated false recognition and item-specific memory as compared to the HC group; moderate-to-severe patients performed more poorly than mild patients did. Only moderate-severe patients exhibited significantly poorer related false recognition index scores than HCs in the verbal DRM task; performance of HD patient groups was comparable to the HC group on the pictorial DRM task. It appears that diminished verbatim memory and monitoring ability are early signs of cognitive decline during the HD course. Conversely, gist memory is relatively robust, with only partial decline during advanced-stage HD. Our findings suggest that medial temporal lobe function is relatively preserved compared to that of frontal-related structures in early HD. Thus, gist-based memory rehabilitation programs might be beneficial for patients with HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Monomeric, Oligomeric and Polymeric Proteins in Huntington Disease and Other Diseases of Polyglutamine Expansion

    Directory of Open Access Journals (Sweden)

    Guylaine Hoffner

    2014-03-01

    Full Text Available Huntington disease and other diseases of polyglutamine expansion are each caused by a different protein bearing an excessively long polyglutamine sequence and are associated with neuronal death. Although these diseases affect largely different brain regions, they all share a number of characteristics, and, therefore, are likely to possess a common mechanism. In all of the diseases, the causative protein is proteolyzed, becomes abnormally folded and accumulates in oligomers and larger aggregates. The aggregated and possibly the monomeric expanded polyglutamine are likely to play a critical role in the pathogenesis and there is increasing evidence that the secondary structure of the protein influences its toxicity. We describe here, with special attention to huntingtin, the mechanisms of polyglutamine aggregation and the modulation of aggregation by the sequences flanking the polyglutamine. We give a comprehensive picture of the characteristics of monomeric and aggregated polyglutamine, including morphology, composition, seeding ability, secondary structure, and toxicity. The structural heterogeneity of aggregated polyglutamine may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective.

  17. Nanopublications for exposing experimental data in the life-sciences: a Huntington's Disease case study.

    Science.gov (United States)

    Mina, Eleni; Thompson, Mark; Kaliyaperumal, Rajaram; Zhao, Jun; der Horst, van Eelke; Tatum, Zuotian; Hettne, Kristina M; Schultes, Erik A; Mons, Barend; Roos, Marco

    2015-01-01

    Data from high throughput experiments often produce far more results than can ever appear in the main text or tables of a single research article. In these cases, the majority of new associations are often archived either as supplemental information in an arbitrary format or in publisher-independent databases that can be difficult to find. These data are not only lost from scientific discourse, but are also elusive to automated search, retrieval and processing. Here, we use the nanopublication model to make scientific assertions that were concluded from a workflow analysis of Huntington's Disease data machine-readable, interoperable, and citable. We followed the nanopublication guidelines to semantically model our assertions as well as their provenance metadata and authorship. We demonstrate interoperability by linking nanopublication provenance to the Research Object model. These results indicate that nanopublications can provide an incentive for researchers to expose data that is interoperable and machine-readable for future use and preservation for which they can get credits for their effort. Nanopublications can have a leading role into hypotheses generation offering opportunities to produce large-scale data integration.

  18. From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

    Directory of Open Access Journals (Sweden)

    Georgios Koutsis

    2014-01-01

    Full Text Available Introduction. Spinocerebellar ataxia 17 (SCA 17 is a rare autosomal dominant cerebellar ataxia (ADCA caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

  19. Separation of uranium(V I) from binary solution mixtures with thorium(IV), zirconium(IV) and cerium(III) by foaming

    International Nuclear Information System (INIS)

    Shakir, K.; Aziz, M.; Benyamin, K.

    1992-01-01

    Foam separation has been investigated for the removal of uranium(V I), thorium(IV), zirconium(IV) and cerium(III) from dilute aqueous solutions at pH values ranging from about I to about II. Sodium laurel sulphate (Na L S) and acetyl trimethyl ammonium bromide (CTAB), being a strong anionic and a strong cationic surfactants, were used as collectors. The results indicate that Na L S can efficiently remove thorium(IV), zirconium(IV) and cerium(III) but not uranium(V I). CTAB, on the other hand, can successfully float only uranium(V I) and zirconium(IV). These differences in flotation properties of the different cations could be used to establish methods for the separation of uranium(V I) from binary mixtures with thorium(IV), zirconium(IV) or cerium(III). The results are discussed in terms of the hydrolytic behaviour of the tested cations and properties of used collectors.2 fig., 1 tab

  20. Generation of induced pluripotent stem cell line, CSSi004-A (2962, from a patient diagnosed with Huntington's disease at the presymptomatic stage

    Directory of Open Access Journals (Sweden)

    Eris Bidollari

    2018-04-01

    Full Text Available Huntington's disease (HD is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype.

  1. IUE observations of interstellar Si IV and C IV lines observed in the spectra of Wolf-Rayet stars

    International Nuclear Information System (INIS)

    Smith, L.J.; Willis, A.J.; Wilson, R.

    1980-01-01

    Recent IUE observations of Wolf-Rayet stars show narrow absorption lines in the highly ionized species of Si IV and C IV. The strengths of these 'interstellar' Si IV and C IV lines observed in the spectra of 10 WR stars and two other early-type stars are compared. Of the WR sample, six stars exhibit very strong Si IV and C IV lines (Wsub(lambda) approximately 0.3 to 0.5 A) whilst the other four stars show much weaker lines (Wsub(lambda) approximately 0.1 A). There is no correlation between the strengths of these lines with either stellar distance or colour excess. The weaker absorptions may arise in the individual stellar H II regions, the observed strengths being consistent with those expected for stars with Tsub(eff) = 30 000 K. Five of the other stars which exhibit very strong absorptions lie in the line of sight to active interstellar regions (Cygnus and Carina nebulae) and it is considered probable that, in addition to their H II region components, the bulk of the strong Si IV and C IV absorptions originate in hot gas associated with these active regions. In the case of the WN5 star HD 50896 violet-displaced components are observed in the interstellar lines of low ionization species. These are thought to be produced in the ring nebula S308 surrounding HD 50896. (author)

  2. Current status of NPP generation IV

    International Nuclear Information System (INIS)

    Yohanes Dwi Anggoro; Dharu Dewi; Nurlaila; Arief Tris Yuliyanto

    2013-01-01

    Today development of nuclear technology has reached the stage of research and development of Generation IV nuclear power plants (advanced reactor systems) which is an innovative development from the previous generation of nuclear power plants. There are six types of power generation IV reactors, namely: Very High Temperature Reactor (VHTR), Sodium-cooled Fast Reactor (SFR), Gas-cooled Fast Reactor (GFR), Lead-cooled Fast Reactor (LFR), Molten Salt Reactor (MSR), and Super Critical Water-cooled Reactor (SCWR). The purpose of this study is to know the development of Generation IV nuclear power plants that have been done by the thirteen countries that are members of the Gen IV International Forum (GIF). The method used is review study and refers to various studies related to the current status of research and development of generation IV nuclear power. The result of this study showed that the systems and technology on Generation IV nuclear power plants offer significant advances in sustainability, safety and reliability, economics, and proliferation resistance and physical protection. In addition, based on the research and development experience is estimated that: SFR can be used optimally in 2015, VHTR in 2020, while NPP types GFR, LFR, MSR, and SCWR in 2025. Utilization of NPP generation IV said to be optimal if fulfill the goal of NPP generation IV, such as: capable to generate energy sustainability and promote long-term availability of nuclear fuel, minimize nuclear waste and reduce the long term stewardship burden, has an advantage in the field of safety and reliability compared to the previous generation of NPP and VHTR technology have a good prospects in Indonesia. (author)

  3. Co-segregation of Huntington disease and hereditary spastic paraplegia in 4 generations.

    Science.gov (United States)

    Panas, Marios; Karadima, Georgia; Kalfakis, Nikolaos; Vassilopoulos, Dimitris

    2011-07-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons.

  4. The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates?

    Science.gov (United States)

    Gil-Mohapel, Joana; Brocardo, Patricia S; Christie, Brian R

    2014-04-01

    Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.

  5. The Development of the Comic Spirit in 17th Century England from James Shirley to William Congreve. Curriculum Projects, April 7-June 16, 1992. The Huntington Theatre Company Master Works Study in Restoration Comedy.

    Science.gov (United States)

    Huntington Theatre Co., Boston, MA.

    Developed by the participants of the Huntington Theatre Company's Master Works Study in Restoration Comedy, this collection presents one-day lesson plans and curriculum projects for teaching Restoration comedy. The collection offers 15 one-day lesson plans and 15 curriculum projects (ranging over several weeks) suitable for secondary school…

  6. Collagen type IV at the fetal-maternal interface.

    Science.gov (United States)

    Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

    2015-01-01

    Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry. Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined. Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. On the Origin of Hobbes’s Conception of Language: The Literary Culture of English Renaissance Humanism

    Directory of Open Access Journals (Sweden)

    Sergio H. Orozco-Echeverri

    2012-12-01

    Full Text Available Hobbes' education in the literary culture of English Renaissance humanism has been overlooked as an important tradition in understanding his position in Early Modern Philosophy. Against the traditional readings of Hobbes' conception of language as a sequel to Medieval nominalism, I will argue that Hobbes' education in the literary culture of Renaissance humanism and his subsequent developments in this tradition would have allowed him to consider philosophical problems raised by new science in an original way and, thus, to introduce his innovative conception of language as the core of his solution to the problem of social and natural orders.

  8. A Si IV/O IV Electron Density Diagnostic for the Analysis of IRIS Solar Spectra

    Science.gov (United States)

    Young, P. R.; Keenan, F. P.; Milligan, R. O.; Peter, H.

    2018-04-01

    Solar spectra of ultraviolet bursts and flare ribbons from the Interface Region Imaging Spectrograph (IRIS) have suggested high electron densities of > {10}12 cm‑3 at transition region temperatures of 0.1 MK, based on large intensity ratios of Si IV λ1402.77 to O IV λ1401.16. In this work, a rare observation of the weak O IV λ1343.51 line is reported from an X-class flare that peaked at 21:41 UT on 2014 October 24. This line is used to develop a theoretical prediction of the Si IV λ1402.77 to O IV λ1401.16 ratio as a function of density that is recommended to be used in the high-density regime. The method makes use of new pressure-dependent ionization fractions that take account of the suppression of dielectronic recombination at high densities. It is applied to two sequences of flare kernel observations from the October 24 flare. The first shows densities that vary between 3× {10}12 and 3× {10}13 cm‑3 over a seven-minute period, while the second location shows stable density values of around 2× {10}12 cm‑3 over a three-minute period.

  9. Batch and column adsorption behaviors of Se(IV) and Te(IV) on organic and inorganic ion exchangers from HCl solutions

    Energy Technology Data Exchange (ETDEWEB)

    El-Sweify, Fatma H.; Abdel-Fattah, Alaa El-Din A.; Aly, Shorouk M.; Ghamry, Mohamed A. [Atomic Energy Authority, Cairo (Egypt). Hot Laboratories Center; El-Sheikh, Ragaa [Zagazig Univ. (Egypt). Chemistry Dept.

    2017-07-01

    Adsorption behaviors of Se(IV) and Te(IV) on the inorganic ion exchanger ceric tungstate (CeW) was studied under static and dynamic conditions and compared with the adsorption on the organic cation and anion exchangers Dowex-50X8 and AG-2X8, respectively. The radioactive isotopes {sup 75}Se and {sup 123m}Te were used to trace the respective elements. Some parameters affecting the adsorption were investigated under static conditions. In the case of batch technique the adsorption was studied from slightly acidic HCl as well as slightly alkaline media, i.e. at two pH-ranges. Se(IV) and Te(IV) were adsorbed on both the inorganic ion exchanger (CeW) and on AG-2X8, from slightly alkaline solutions. From the similarity of adsorption on both ion exchangers it was clear that (CeW) acts as an anion exchanger. Moreover, the obtained K{sub d}-values for the adsorption on (CeW) were much higher than those for the adsorption on the organic anion exchanger AG-2X8. Se(IV) was not adsorbed on Dowex-50X8 all over the studied pH-range whereas Te(IV) was slightly adsorbed. Loading and elution behaviors of Se(IV) and Te(IV) on columns of AG-2X8 and (CeW) were studied using solutions of HCl of different concentrations. Some good separation alternatives of Se(IV) and Te(IV) under certain conditions were achieved.

  10. Predicting DPP-IV inhibitors with machine learning approaches

    Science.gov (United States)

    Cai, Jie; Li, Chanjuan; Liu, Zhihong; Du, Jiewen; Ye, Jiming; Gu, Qiong; Xu, Jun

    2017-04-01

    Dipeptidyl peptidase IV (DPP-IV) is a promising Type 2 diabetes mellitus (T2DM) drug target. DPP-IV inhibitors prolong the action of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), improve glucose homeostasis without weight gain, edema, and hypoglycemia. However, the marketed DPP-IV inhibitors have adverse effects such as nasopharyngitis, headache, nausea, hypersensitivity, skin reactions and pancreatitis. Therefore, it is still expected for novel DPP-IV inhibitors with minimal adverse effects. The scaffolds of existing DPP-IV inhibitors are structurally diversified. This makes it difficult to build virtual screening models based upon the known DPP-IV inhibitor libraries using conventional QSAR approaches. In this paper, we report a new strategy to predict DPP-IV inhibitors with machine learning approaches involving naïve Bayesian (NB) and recursive partitioning (RP) methods. We built 247 machine learning models based on 1307 known DPP-IV inhibitors with optimized molecular properties and topological fingerprints as descriptors. The overall predictive accuracies of the optimized models were greater than 80%. An external test set, composed of 65 recently reported compounds, was employed to validate the optimized models. The results demonstrated that both NB and RP models have a good predictive ability based on different combinations of descriptors. Twenty "good" and twenty "bad" structural fragments for DPP-IV inhibitors can also be derived from these models for inspiring the new DPP-IV inhibitor scaffold design.

  11. Spectroscopy study of ceramic pigments based on Ce(IV)-Pr(IV) oxide

    International Nuclear Information System (INIS)

    Furtado, L.; Toma, H.E.

    1991-01-01

    The synthesis and spectroscopic properties of a series of cerium(IV)-praseodimium(IV) oxide pigments are reported. The pigments exhibit brick-red colours and are suitable for ceramic applications because of their high temperature stability. Electronic absorption spectra of the pigments suspended in a gel matrix of polyvinyl alcohol-sodium tetradecaborate mixture, consists of broad band with gaussian components at 372 and 472nm. These bands are described to charge -transfer transitions from the occupied oxygen p-orbitals to the empty f levels of the lanthanides. (author)

  12. Predictors of Workplace Disability in a Premanifest Huntington's Disease Cohort.

    Science.gov (United States)

    Goh, Anita M Y; You, Emily; Perin, Stephanie; Clay, Fiona J; Loi, Samantha; Ellis, Kathryn; Chong, Terence; Ames, David; Lautenschlager, Nicola

    2018-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, and psychiatric/behavioral impairments that will eventually affect work role functioning. Few objective data exist regarding predictors of workplace disability in HD. The authors explored the predictors of work impairment and disability in a cross-sectional cohort of 656 employed, premanifest HD (preHD) individuals. In this cohort-the majority of whom were female, urban-dwelling, married/partnered, and working full-time, with minimal cognitive impairment, good function, minimal motor abnormality, and no indication of significant mental health issues-the number of participants who reported that they had missed work due to HD was low (2.4%). However, 12% of the study sample reported experiencing impairment while working due to preHD, 12.2% reported work-related activity impairment due to preHD, and 12.7% reported impairment in their overall work ability. Higher numbers of CAG repeats on the mutant allele and having more motor symptoms were associated with significantly higher odds of experiencing workplace impairment. Importantly, several modifiable factors were also found to predict workplace disability. Specifically, higher levels of anxiety symptoms were associated with significantly higher odds of experiencing workplace impairment. Good mental and physical health served as protective factors, where good physical health was associated with 6% lower odds of experiencing impairment or missing work time and good mental health was associated with of 10%-12% lower. The results provide important new knowledge for the development of future targeted intervention trials to support preHD individuals in maintaining their work roles as long as possible.

  13. Drosophila eye color mutants as therapeutic tools for Huntington disease.

    Science.gov (United States)

    Green, Edward W; Campesan, Susanna; Breda, Carlo; Sathyasaikumar, Korrapati V; Muchowski, Paul J; Schwarcz, Robert; Kyriacou, Charalambos P; Giorgini, Flaviano

    2012-01-01

    Huntington disease (HD) is a fatal inherited neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein (htt). A pathological hallmark of the disease is the loss of a specific population of striatal neurons, and considerable attention has been paid to the role of the kynurenine pathway (KP) of tryptophan (TRP) degradation in this process. The KP contains three neuroactive metabolites: 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and kynurenic acid (KYNA). 3-HK and QUIN are neurotoxic, and are increased in the brains of early stage HD patients, as well as in yeast and mouse models of HD. Conversely, KYNA is neuroprotective and has been shown to be decreased in HD patient brains. We recently used a Drosophila model of HD to measure the neuroprotective effect of genetic and pharmacological inhibition of kynurenine monoxygenase (KMO)-the enzyme catalyzing the formation of 3-HK at a pivotal branch point in the KP. We found that KMO inhibition in Drosophila robustly attenuated neurodegeneration, and that this neuroprotection was correlated with reduced levels of 3-HK relative to KYNA. Importantly, we showed that KP metabolites are causative in this process, as 3-HK and KYNA feeding experiments modulated neurodegeneration. We also found that genetic inhibition of the upstream KP enzyme tryptophan-2,3-dioxygenase (TDO) was neuroprotective in flies. Here, we extend these results by reporting that genetic impairment of KMO or TDO is protective against the eclosion defect in HD model fruit flies. Our results provide further support for the possibility of therapeutic KP interventions in HD.

  14. 1L Mark-IV Target Design Review

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-16

    This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

  15. Investigating the reasons of variability in Si IV and C IV broad absorption line troughs of quasars

    Science.gov (United States)

    Stathopoulos, Dimitrios; Lyratzi, Evangelia; Danezis, Emmanuel; Antoniou, Antonios; Tzimeas, Dimitrios

    2017-09-01

    In this paper we analyze the C IV and Si IV broad absorption troughs of two BALQSOs (J101056.69+355833.3, J114548.38+393746.6) to the individual components they consist of. By analyzing a BAL trough to its components we have the advantage to study the variations of the individual absorbing systems in the line of sight and not just the variations of the whole absorption trough or the variations of selected portions of BAL troughs exhibiting changes. We find that the velocity shifts and FWHMs (Full Width at Half Maximum) of the individual components do not vary between an interval of six years. All variable components show changes in the optical depths at line centers which are manifested as variations in the EW (Equivalent Width) of the components. In both BALQSOs, over corresponding velocities, Si IV has higher incidence of variability than C IV. From our analysis, evidence is in favour of different covering fractions between C IV and Si IV. Finally, although most of our results favour the crossing cloud scenario as the cause of variability, there is also strong piece of evidence indicating changing ionization as the source of variability. Thus, a mixed situation where both physical mechanisms contribute to BAL variability is the most possible scenario.

  16. 33 CFR 116.45 - Submission of bids, approval of award, guaranty of cost, and partial payments for bridges...

    Science.gov (United States)

    2010-07-01

    ... award, guaranty of cost, and partial payments for bridges eligible for funding under the Truman-Hobbs... SECURITY BRIDGES ALTERATION OF UNREASONABLY OBSTRUCTIVE BRIDGES § 116.45 Submission of bids, approval of award, guaranty of cost, and partial payments for bridges eligible for funding under the Truman-Hobbs...

  17. Topological characterisation and identification of critical domains within glucosyltransferase IV (GtrIV of Shigella flexneri

    Directory of Open Access Journals (Sweden)

    Nair Anesh

    2011-12-01

    Full Text Available Abstract Background The three bacteriophage genes gtrA, gtrB and gtr(type are responsible for O-antigen glucosylation in Shigella flexneri. Both gtrA and gtrB have been demonstrated to be highly conserved and interchangeable among serotypes while gtr(type was found to be specific to each serotype, leading to the hypothesis that the Gtr(type proteins are responsible for attaching glucosyl groups to the O-antigen in a site- and serotype- specific manner. Based on the confirmed topologies of GtrI, GtrII and GtrV, such interaction and attachment of the glucosyl groups to the O-antigen has been postulated to occur in the periplasm. Results In this study, the topology of GtrIV was experimentally determined by creating different fusions between GtrIV and a dual-reporter protein, PhoA/LacZ. This study shows that GtrIV consists of 8 transmembrane helices, 2 large periplasmic loops, 2 small cytoplasmic N- and C- terminal ends and a re-entrant loop that occurs between transmembrane helices III and IV. Though this topology differs from that of GtrI, GtrII, GtrV and GtrX, it is very similar to that of GtrIc. Furthermore, both the N-terminal periplasmic and the C-terminal periplasmic loops are important for GtrIV function as shown via a series of loop deletion experiments and the creation of chimeric proteins between GtrIV and its closest structural homologue, GtrIc. Conclusion The current study provides the basis for elucidating the structure and mechanism of action of this important O-antigen modifying glucosyltransferase.

  18. Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography

    International Nuclear Information System (INIS)

    Leenders, K.L.; Frackowiak, R.S.; Quinn, N.; Marsden, C.D.

    1986-01-01

    A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilization, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilization paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[ 18 F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects

  19. Generation of induced pluripotent stem cells from transgenic minipigs expressing the N-terminal part of the human mutant huntingtin - a new way to study pathogenesis of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Lišková, Irena; Vodička, P.; Juhás, Štefan; Klempíř, J.; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 18-19 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * huntingtin * induced pluripotent stem cells Subject RIV: FH - Neurology

  20. Single-layer group IV-V and group V-IV-III-VI semiconductors: Structural stability, electronic structures, optical properties, and photocatalysis

    Science.gov (United States)

    Lin, Jia-He; Zhang, Hong; Cheng, Xin-Lu; Miyamoto, Yoshiyuki

    2017-07-01

    Recently, single-layer group III monochalcogenides have attracted both theoretical and experimental interest at their potential applications in photonic devices, electronic devices, and solar energy conversion. Excited by this, we theoretically design two kinds of highly stable single-layer group IV-V (IV =Si ,Ge , and Sn; V =N and P) and group V-IV-III-VI (IV =Si ,Ge , and Sn; V =N and P; III =Al ,Ga , and In; VI =O and S) compounds with the same structures with single-layer group III monochalcogenides via first-principles simulations. By using accurate hybrid functional and quasiparticle methods, we show the single-layer group IV-V and group V-IV-III-VI are indirect bandgap semiconductors with their bandgaps and band edge positions conforming to the criteria of photocatalysts for water splitting. By applying a biaxial strain on single-layer group IV-V, single-layer group IV nitrides show a potential on mechanical sensors due to their bandgaps showing an almost linear response for strain. Furthermore, our calculations show that both single-layer group IV-V and group V-IV-III-VI have absorption from the visible light region to far-ultraviolet region, especially for single-layer SiN-AlO and SnN-InO, which have strong absorption in the visible light region, resulting in excellent potential for solar energy conversion and visible light photocatalytic water splitting. Our research provides valuable insight for finding more potential functional two-dimensional semiconductors applied in optoelectronics, solar energy conversion, and photocatalytic water splitting.

  1. Tremor in neurodegenerative ataxias, Huntington disease and tic disorder.

    Science.gov (United States)

    Rudzińska, M; Krawczyk, M; Wójcik-Pędziwiatr, M; Szczudlik, A; Tomaszewski, T

    2013-01-01

    Tremor is the most prevalent movement disorder, defined as rhythmic oscillations of a body part, caused by alternating or synchronic contractions of agonistic or antagonistic muscles. The aim of the study was to assess prevalence and to characterize parameters of tremor accompanying de-generative ataxias, Huntington disease (HD) and tic disorders in comparison with a control group. Forty-three patients with degenerative ataxias, 28 with HD and 26 with tic disorders together with 51 healthy controls were included in the study. For each participant, clinical and instrumental assessment (accelerometer, electromyography [EMG], graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor), with hands extended (postural tremor), during the 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, the type of tremor was determined as essential tremor type or enhanced physiological tremor type. The incidence of tremor in the accelerometry in patients with degenerative ataxia (50%) significantly differs from controls (10%) (p = 0.001). The dominant tremor was postural, low-intense, with 7-Hz frequency, essential tremor (23%) or other tremor type (23%), while enhanced physiological tremor was the least frequent (2%). Tremor in patients with HD and tic disorders was found in 10% and 20% of patients, respectively, similarly to the control group. Tremor was mild, postural and of essential tremor type, less frequently of enhanced physiological tremor type. No correlation between severity of tremor and severity of disease was found. The prevalence of tremor is considerably higher among patients with degenerative ataxias compared with HD, tic disorder and the control group. The most common type of tremor accompanying ataxias, HD and tic disorders is essential tremor type.

  2. Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington's disease knock-in striatal cells.

    Science.gov (United States)

    Ribeiro, Márcio; Rosenstock, Tatiana R; Oliveira, Ana M; Oliveira, Catarina R; Rego, A Cristina

    2014-09-01

    Oxidative stress and mitochondrial dysfunction have been described in Huntington's disease, a disorder caused by expression of mutant huntingtin (mHtt). IGF-1 was previously shown to protect HD cells, whereas insulin prevented neuronal oxidative stress. In this work we analyzed the role of insulin and IGF-1 in striatal cells derived from HD knock-in mice on mitochondrial production of reactive oxygen species (ROS) and related antioxidant and signaling pathways influencing mitochondrial function. Insulin and IGF-1 decreased mitochondrial ROS induced by mHtt and normalized mitochondrial SOD activity, without affecting intracellular glutathione levels. IGF-1 and insulin promoted Akt phosphorylation without changing the nuclear levels of phosphorylated Nrf2 or Nrf2/ARE activity. Insulin and IGF-1 treatment also decreased mitochondrial Drp1 phosphorylation, suggesting reduced mitochondrial fragmentation, and ameliorated mitochondrial function in HD cells in a PI-3K/Akt-dependent manner. This was accompanied by increased total and phosphorylated Akt, Tfam, and mitochondrial-encoded cytochrome c oxidase II, as well as Tom20 and Tom40 in mitochondria of insulin- and IGF-1-treated mutant striatal cells. Concomitantly, insulin/IGF-1-treated mutant cells showed reduced apoptotic features. Hence, insulin and IGF-1 improve mitochondrial function and reduce mitochondrial ROS caused by mHtt by activating the PI-3K/Akt signaling pathway, in a process independent of Nrf2 transcriptional activity, but involving enhanced mitochondrial levels of Akt and mitochondrial-encoded complex IV subunit. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Advances in the understanding of early Huntington's disease using the functional imaging techniques of PET and SPET

    International Nuclear Information System (INIS)

    Andrews, T.C.; Brooks, D.J.

    1998-01-01

    The functional imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPET) have been used to study regional brain function in Huntington's disease (HD) in vivo. Reduced striatal glucose metabolism and dopamine receptor binding are evident in all symptomatic HD patients and in ∼50% of asymptomatic adult mutation carriers. These characteristics correlate with clinical measures of disease severity. Reduced cortical glucose metabolism and dopamine receptor binding, together with reduced striatal and cortical opioid receptor binding, have also been demonstrated in symptomatic patients with HD. Repeat PET measures of striatal function have been used to monitor the progression of this disease objectively. In the future, functional imaging will provide a valuable way of assessing the efficacy of both fetal striatal cell implants and putative neuroprotective agents, such as nerve growth factors. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  4. Targeting kynurenine 3-monooxygenase (KMO): implications for therapy in Huntington's disease.

    Science.gov (United States)

    Thevandavakkam, Mathuravani A; Schwarcz, Robert; Muchowski, Paul J; Giorgini, Flaviano

    2010-12-01

    Huntington's disease (HD) is an adult onset neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. Recent work has shown that perturbation of kynurenine pathway (KP) metabolism is a hallmark of HD pathology, and that changes in brain levels of KP metabolites may play a causative role in this disease. The KP contains three neuroactive metabolites, the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN), and the neuroprotectant kynurenic acid (KYNA). In model systems in vitro and in vivo, 3-HK and QUIN have been shown to cause neurodegeneration via a combination of excitotoxic mechanisms and oxidative stress. Recent studies with HD patient samples and in HD model systems have supported the idea that a shift away from the synthesis of KYNA and towards the formation of 3-HK and QUIN may trigger the neuropathological features observed in HD. The enzyme kynurenine 3-monooxygenase (KMO) is located at a critical branching point in the KP such that inhibition of this enzyme by either pharmacological or genetic means shifts the flux in the pathway towards the formation of KYNA. This intervention ameliorates disease-relevant phenotypes in HD models. Here we review the work implicating the KP in HD pathology and discuss the potential of KMO as a therapeutic target for this disorder. As several neurodegenerative diseases exhibit alterations in KP metabolism, this concept has broader implications for the treatment of brain diseases.

  5. Theory of mind and empathy in preclinical and clinical Huntington's disease.

    Science.gov (United States)

    Adjeroud, Najia; Besnard, Jérémy; El Massioui, Nicole; Verny, Christophe; Prudean, Adriana; Scherer, Clarisse; Gohier, Bénédicte; Bonneau, Dominique; Allain, Philippe

    2016-01-01

    We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington's disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054-67) that examines first- and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first- and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Glycogen Storage Disease Type IV

    DEFF Research Database (Denmark)

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B

    2016-01-01

    molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made...

  7. IV&V Project Assessment Process Validation

    Science.gov (United States)

    Driskell, Stephen

    2012-01-01

    The Space Launch System (SLS) will launch NASA's Multi-Purpose Crew Vehicle (MPCV). This launch vehicle will provide American launch capability for human exploration and travelling beyond Earth orbit. SLS is designed to be flexible for crew or cargo missions. The first test flight is scheduled for December 2017. The SLS SRR/SDR provided insight into the project development life cycle. NASA IV&V ran the standard Risk Based Assessment and Portfolio Based Risk Assessment to identify analysis tasking for the SLS program. This presentation examines the SLS System Requirements Review/System Definition Review (SRR/SDR), IV&V findings for IV&V process validation correlation to/from the selected IV&V tasking and capabilities. It also provides a reusable IEEE 1012 scorecard for programmatic completeness across the software development life cycle.

  8. Dissimilatory Fe(III) and Mn(IV) reduction.

    Science.gov (United States)

    Lovley, D R

    1991-06-01

    The oxidation of organic matter coupled to the reduction of Fe(III) or Mn(IV) is one of the most important biogeochemical reactions in aquatic sediments, soils, and groundwater. This process, which may have been the first globally significant mechanism for the oxidation of organic matter to carbon dioxide, plays an important role in the oxidation of natural and contaminant organic compounds in a variety of environments and contributes to other phenomena of widespread significance such as the release of metals and nutrients into water supplies, the magnetization of sediments, and the corrosion of metal. Until recently, much of the Fe(III) and Mn(IV) reduction in sedimentary environments was considered to be the result of nonenzymatic processes. However, microorganisms which can effectively couple the oxidation of organic compounds to the reduction of Fe(III) or Mn(IV) have recently been discovered. With Fe(III) or Mn(IV) as the sole electron acceptor, these organisms can completely oxidize fatty acids, hydrogen, or a variety of monoaromatic compounds. This metabolism provides energy to support growth. Sugars and amino acids can be completely oxidized by the cooperative activity of fermentative microorganisms and hydrogen- and fatty-acid-oxidizing Fe(III) and Mn(IV) reducers. This provides a microbial mechanism for the oxidation of the complex assemblage of sedimentary organic matter in Fe(III)- or Mn(IV)-reducing environments. The available evidence indicates that this enzymatic reduction of Fe(III) or Mn(IV) accounts for most of the oxidation of organic matter coupled to reduction of Fe(III) and Mn(IV) in sedimentary environments. Little is known about the diversity and ecology of the microorganisms responsible for Fe(III) and Mn(IV) reduction, and only preliminary studies have been conducted on the physiology and biochemistry of this process.

  9. Assembling filamentous phage occlude pIV channels.

    Science.gov (United States)

    Marciano, D K; Russel, M; Simon, S M

    2001-07-31

    Filamentous phage f1 is exported from its Escherichia coli host without killing the bacterial cell. Phage-encoded protein pIV, which is required for phage assembly and secretion, forms large highly conductive channels in the outer membrane of E. coli. It has been proposed that the phage are extruded across the bacterial outer membrane through pIV channels. To test this prediction, we developed an in vivo assay by using a mutant pIV that functions in phage export but whose channel opens in the absence of phage extrusion. In E. coli lacking its native maltooligosacharride transporter LamB, this pIV variant allowed oligosaccharide transport across the outer membrane. This entry of oligosaccharide was decreased by phage production and still further decreased by production of phage that cannot be released from the cell surface. Thus, exiting phage block the pIV-dependent entry of oligosaccharide, suggesting that phage occupy the lumen of pIV channels. This study provides the first evidence, to our knowledge, for viral exit through a large aqueous channel.

  10. Non-equilibrium ionization by a periodic electron beam. II. Synthetic Si IV and O IV transition region spectra

    Science.gov (United States)

    Dzifčáková, Elena; Dudík, Jaroslav

    2018-03-01

    Context. Transition region (TR) spectra typically show the Si IV 1402.8 Å line to be enhanced by a factor of 5 or more compared to the neighboring O IV 1401.2 Å, contrary to predictions of ionization equilibrium models and the Maxwellian distribution of particle energies. Non-equilibrium effects in TR spectra are therefore expected. Aims: To investigate the combination of non-equilibrium ionization and high-energy particles, we apply the model of the periodic electron beam, represented by a κ-distribution that recurs at periods of several seconds, to plasma at chromospheric temperatures of 104 K. This simple model can approximate a burst of energy release involving accelerated particles. Methods: Instantaneous time-dependent charge states of silicon and oxygen were calculated and used to synthesize the instantaneous and period-averaged spectra of Si IV and O IV. Results: The electron beam drives the plasma out of equilibrium. At electron densities of Ne = 1010 cm-3, the plasma is out of ionization equilibrium at all times in all cases we considered, while for a higher density of Ne = 1011 cm-3, ionization equilibrium can be reached toward the end of each period, depending on the conditions. In turn, the character of the period-averaged synthetic spectra also depends on the properties of the beam. While the case of κ = 2 results in spectra with strong or even dominant O IV, higher values of κ can approximate a range of observed TR spectra. Spectra similar to typically observed spectra, with the Si IV 1402.8 Å line about a factor 5 higher than O IV 1401.2 Å, are obtained for κ = 3. An even higher value of κ = 5 results in spectra that are exclusively dominated by Si IV, with negligible O IV emission. This is a possible interpretation of the TR spectra of UV (Ellerman) bursts, although an interpretation that requires a density that is 1-3 orders of magnitude lower than for equilibrium estimates. Movies associated to Fig. A.1 are available at http://https://www.aanda.org

  11. A Case of Attempted Suicide in Huntington's Disease: Ethical and Moral Considerations.

    Science.gov (United States)

    Furfari, Kristin; Zehnder, Nichole; Abbott, Jean

    2016-01-01

    A 62-year-old female with Huntington's disease presented after a suicide attempt. Her advance directive stated that she did not want intubation or resuscitation, which her family acknowledged and supported. Despite these directives, she was resuscitated in the emergency department and continued to state that she would attempt suicide again. Her suicidality in the face of a chronic and advancing illness, and her prolonged consistency in her desire to take her own life, left careproviders wondering how to provide ethical, respectful care to this patient. Tension between the ethical principles of autonomy and beneficence is central in this case. The patient's narrative demonstrated that her suicide was an autonomous decision, free from coercion or disordered thinking from mental illness. Beneficence then would seem to necessitate care aligned with the patient's desire to end her life, which created ethical uneasiness for her family and careproviders. The case highlights several end-of-life ethical considerations that have received much recent attention. With ongoing discussions about the legalization of aid in dying across the country, caregivers are challenged to understand what beneficence means in people with terminal illnesses who want a say in their death. This case also highlights the profound moral distress of families and careproviders that arises in such ethically challenging scenarios. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

  12. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  13. Solubility study of Tc(IV) oxides

    International Nuclear Information System (INIS)

    Liu, D.J.; Fan, X.H.

    2005-01-01

    The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under oxidizing conditions technetium exists as the anionic species TcO 4 - whereas under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 ·nH 2 O. Hence, the mobility of Tc(IV) in reducing groundwater may be limited by the solubility of TcO 2 ·nH 2 O under these conditions. Due to this fact it is important to investigate the solubility of TcO 2 ·nH 2 O. The solubility determines the release of radionuclides from waste form and is used as a source term in radionuclide migration analysis in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2 + . The solubility of Tc(IV) oxide has been determined in simulated groundwater and redistilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and redistilled water is about (1.49-1.86) x 10 -9 mol/(L·d) under aerobic conditions, but Tc(IV) in simulated groundwater and redistilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and redistilled water is equal on the whole after centrifugation or ultrafiltration. The

  14. The Contribution of IVS to IGGOS

    Science.gov (United States)

    Nothnagel, A.

    2002-05-01

    Since its inauguration in 1999, the International VLBI Service for Geodesy and Astrometry has made significant progress in the coordination and utilisation of worldwide VLBI resources. Improving the visibility of the IVS components to a wider public in turn led to a higher motivation of the individuals to contribute to the global effort. Not only the number of IVS components but also their investments in terms of funds and manpower demonstrate the increased awareness of the importance of this joint international endeavour. The different demands of the users but also of the contributors often require the definition of priorities which are only being acceptable due to the existence of a strong umbrella organisation like the IVS. Significant progress has also been made in the area of routine data analysis and combination of results. By now, six IVS Analysis Centers provide the redundancy necessary for a robust combination of the results. The use of ITRF2000 station coordinates as the basis for the IVS combined EOP series is the most recent step towards the generation of a consistent chain from the quasi-inertial frame of radio sources to system Earth.

  15. Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies.

    Science.gov (United States)

    Bartlett, Danielle M; Cruickshank, Travis M; Hannan, Anthony J; Eastwood, Peter R; Lazar, Alpar S; Ziman, Mel R

    2016-12-01

    Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Daniel Todd

    Full Text Available Huntington's disease (HD is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models.

  17. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  18. EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease.

    Science.gov (United States)

    Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

    2013-05-01

    Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these laboratories, the European Molecular Genetics Quality Network has organized a yearly external quality assessment (EQA) scheme for molecular genetic testing of HD for over 10 years. EQA compares a laboratory's output with a fixed standard both for genotyping and reporting of the results to the referring physicians. In general, the standard of genotyping is very high but the clarity of interpretation and reporting of the test result varies more widely. This emphasizes the need for best practice guidelines for this disorder. We have therefore developed these best practice guidelines for genetic testing for HD to assist in testing and reporting of results. The analytical methods and the potential pitfalls of molecular genetic testing are highlighted and the implications of the different test outcomes for the consultand and his or her family members are discussed.

  19. The Medicinal Chemistry of Natural and Semisynthetic Compounds against Parkinson's and Huntington's Diseases.

    Science.gov (United States)

    Zanforlin, Enrico; Zagotto, Giuseppe; Ribaudo, Giovanni

    2017-11-15

    Among the diseases affecting the central nervous system (CNS), neurodegenerations attract the interest of both the clinician and the medicinal chemist. The increasing average age of population, the growing number of patients, and the lack of long-term effective remedies push ahead the quest for novel tools against this class of pathologies. We present a review on the state of the art of the molecules (or combination of molecules) of natural origin that are currently under study against two well-defined pathologies: Parkinson's disease (PD) and Huntington's disease (HD). Nowadays, very few tools are available for preventing or counteracting the progression of such diseases. Two major parameters were considered for the preparation of this review: particular attention was reserved to these research works presenting well-defined molecular mechanisms for the studied compounds, and where available, papers reporting in vivo data were preferred. A literature search for peer-reviewed articles using PubMed, Scopus, and Reaxys databases was performed, exploiting different keywords and logical operators: 91 papers were considered (preferentially published after 2015). The review presents a brief overview on the etiology of the studied neurodegenerations and the current treatments, followed by a detailed discussion of the natural and semisynthetic compounds dividing them in different paragraphs considering their several mechanisms of action.

  20. Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.

    Science.gov (United States)

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner.

  1. Purification, identification and molecular mechanism of two dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Antarctic krill (Euphausia superba) protein hydrolysate.

    Science.gov (United States)

    Ji, Wei; Zhang, Chaohua; Ji, Hongwu

    2017-10-01

    Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC). DPP-IV inhibitory activity of the fractions achieved from Antarctic krill protein was determined by DPP-IV screening reagent kit. Two purified peptides were identified by Xevo G2-XS QTof mass spectrometer (QTOF-MS). One peptide purified was Ala-Pro (AP) with IC 50 values of 0.0530mg/mL, the other Ile-Pro-Ala (IPA) with IC 50 values of 0.0370mg/mL. They both exhibited strong DPP-IV inhibitory activity. The molecular docking analysis revealed that DPP-IV inhibition by AP and IPA was mainly due to formation of a strong interaction surface force with the 91-96 and 101-105 amino acids of the DPP-IV. Our results suggested that the protein hydrolysate from Antarctic krill can be considered as a promising natural source of DPP-IV inhibitory peptides in the management of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. On the Importance of the Nonequilibrium Ionization of Si IV and O IV and the Line of Sight in Solar Surges

    Science.gov (United States)

    Nóbrega-Siverio, D.; Moreno-Insertis, F.; Martínez-Sykora, J.

    2018-05-01

    Surges are ubiquitous cool ejections in the solar atmosphere that often appear associated with transient phenomena like UV bursts or coronal jets. Recent observations from the Interface Region Imaging Spectrograph show that surges, although traditionally related to chromospheric lines, can exhibit enhanced emission in Si IV with brighter spectral profiles than for the average transition region (TR). In this paper, we explain why surges are natural sites to show enhanced emissivity in TR lines. We performed 2.5D radiative-MHD numerical experiments using the Bifrost code including the nonequilibrium (NEQ) ionization of silicon and oxygen. A surge is obtained as a by-product of magnetic flux emergence; the TR enveloping the emerged domain is strongly affected by NEQ effects: assuming statistical equilibrium would produce an absence of Si IV and O IV ions in most of the region. Studying the properties of the surge plasma emitting in the Si IV λ1402.77 and O IV λ1401.16 lines, we find that (a) the timescales for the optically thin losses and heat conduction are very short, leading to departures from statistical equilibrium, and (b) the surge emits in Si IV more and has an emissivity ratio of Si IV to O IV larger than a standard TR. Using synthetic spectra, we conclude the importance of line-of-sight effects: given the involved geometry of the surge, the line of sight can cut the emitting layer at small angles and/or cross it multiple times, causing prominent, spatially intermittent brightenings in both Si IV and O IV.

  3. Synthesis and spectroscopic studies of mono- and dicyclopentadienyl titanium (IV)/zirconium (IV) derivatives with S-alkyl-β-N-(acetylferrocenyl) methylene dithiocarbazates

    International Nuclear Information System (INIS)

    Srivastava, B.K.; Srivastava, S.K.; Pandey, O.P.; Sengupta, S.K.

    1996-01-01

    The reactions of dicyclopentadienyl titanium (IV)/zirconium (IV) dichloride and monocyclopentadienyl titanium (IV) trichloride with thio-Schiff bases (LH), derived by the condensation of S-methyl/ethyl/propyl dithiocarbazic acid and acetylferrocene have been carried out under inert atmosphere and anhydrous conditions in different stoichiometric ratios. Complexes of the types Cp 2 M(L)Cl, CpM(L) 2 Cl (M= Ti(IV) or Zr(IV)), CpTi(L)Cl 2 , CpTi(L) 2 Cl are synthesised and characterized by elemental analysis, electrical conductance, magnetic moment and spectral (electronic, infrared, 1 H NMR) data. (author). 12 refs., 1 tab

  4. SAGE IV Pathfinder

    Data.gov (United States)

    National Aeronautics and Space Administration — Utilizing a unique, new occultation technique involving imaging, the SAGE IV concept will meet or exceed the quality of previous SAGE measurements at a small...

  5. Facile and reversible formation of iron(III)-oxo-cerium(IV) adducts from nonheme oxoiron(IV) complexes and cerium(III)

    Energy Technology Data Exchange (ETDEWEB)

    Draksharapu, Apparao; Rasheed, Waqas; Klein, Johannes E.M.N.; Que, Lawrence Jr. [Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN (United States)

    2017-07-24

    Ceric ammonium nitrate (CAN) or Ce{sup IV}(NH{sub 4}){sub 2}(NO{sub 3}){sub 6} is often used in artificial water oxidation and generally considered to be an outer-sphere oxidant. Herein we report the spectroscopic and crystallographic characterization of [(N4Py)Fe{sup III}-O-Ce{sup IV}(OH{sub 2})(NO{sub 3}){sub 4}]{sup +} (3), a complex obtained from the reaction of [(N4Py)Fe{sup II}(NCMe)]{sup 2+} with 2 equiv CAN or [(N4Py)Fe{sup IV}=O]{sup 2+} (2) with Ce{sup III}(NO{sub 3}){sub 3} in MeCN. Surprisingly, the formation of 3 is reversible, the position of the equilibrium being dependent on the MeCN/water ratio of the solvent. These results suggest that the Fe{sup IV} and Ce{sup IV} centers have comparable reduction potentials. Moreover, the equilibrium entails a change in iron spin state, from S=1 Fe{sup IV} in 2 to S=5/2 in 3, which is found to be facile despite the formal spin-forbidden nature of this process. This observation suggests that Fe{sup IV}=O complexes may avail of reaction pathways involving multiple spin states having little or no barrier. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Progressive microstructural changes of the occipital cortex in Huntington's disease.

    Science.gov (United States)

    Odish, Omar F F; Reijntjes, Robert H A M; van den Bogaard, Simon J A; Roos, Raymund A C; Leemans, Alexander

    2018-02-28

    In this study we longitudinally investigated the rate of microstructural alterations in the occipital cortex in different stages of Huntington's disease (HD) by applying an automated atlas-based approach to diffusion MRI data. Twenty-two premanifest (preHD), 10 early manifest HD (early HD) and 24 healthy control subjects completed baseline and two year follow-up scans. The preHD group was stratified based on the predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. Clinical and behavioral measures were collected per assessment time point. An automated atlas-based DTI analysis approach was used to obtain the mean, axial and radial diffusivities of the occipital cortex. We found that the longitudinal rate of diffusivity change in the superior occipital gyrus (SOG), middle occipital gyrus (MOG), and inferior occipital gyrus (IOG) was significantly higher in early HD compared to both preHD and controls (all p's ≤ 0.005), which can be interpreted as an increased rate of microstructural degeneration. Furthermore, the change rate in the diffusivity of the MOG could significantly discriminate between preHD-B compared to preHD-A and the other groups (all p's ≤ 0.04). Finally, we found an inverse correlation between the Stroop Word Reading task and diffusivities in the SOG and MOG (all p's ≤ 0.01). These findings suggest that measures obtained from the occipital cortex can serve as sensitive longitudinal biomarkers for disease progression in preHD-B and early HD. These could in turn be used to assess potential effects of proposed disease modifying therapies.

  7. Plasma metabolism of apolipoprotein A-IV in humans

    International Nuclear Information System (INIS)

    Ghiselli, G.; Krishnan, S.; Beigel, Y.; Gotto, A.M. Jr.

    1986-01-01

    As assessed by molecular sieve chromatography and quantitation by a specific radioimmunoassay, apoA-IV is associated in plasma with the triglyceride-rich lipoproteins, to a high density lipoprotein (HDL) subfraction of smaller size than HDL3, and to the plasma lipoprotein-free fraction (LFF). In this study, the turnover of apoA-IV associated to the triglyceride-rich lipoproteins, HDL and LFF was investigated in vivo in normal volunteers. Human apoA-IV isolated from the thoracic duct lymph chylomicrons was radioiodinated and incubated with plasma withdrawn from normal volunteers after a fatty meal. Radioiodinated apoA-IV-labeled triglyceride-rich lipoproteins, HDL, and LFF were then isolated by chromatography on an AcA 34 column. Shortly after the injection of the radioiodinated apoA-IV-labeled triglyceride-rich lipoproteins, most of the radioactivity could be recovered in the HDL and LFF column fractions. On the other hand, when radioiodinated apoA-IV-labeled HDL or LFF were injected, the radioactivity remained with the originally injected fractions at all times. The residence time in plasma of 125 I-labeled apoA-IV, when injected in association with HDL or LFF, was 1.61 and 0.55 days, respectively. When 125 I-labeled apoA-IV was injected as a free protein, the radioactivity distributed rapidly among the three plasma pools in proportion to their mass. The overall fractional catabolic rate of apoA-IV in plasma was measured in the three normal subjects and averaged 1.56 pools per day. The mean degradation rate of apoA-IV was 8.69 mg/kg X day

  8. Collagen type IV at the fetal-maternal interface

    OpenAIRE

    Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

    2015-01-01

    Introduction Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Methods Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle ...

  9. VENDED UM-JINGIR

    African Journals Online (AJOL)

    Dr. Nazik E. M. Mustafa

    2011-09-05

    Sep 5, 2011 ... 2. Khartoum State Ministry of Health, P.O. Box 303 Khartoum, Sudan ... Um-Jingir is a fermented indigenous Sudanese food product made mainly from ... street vended Um-Jingir might have negative effects on public health. Therefore ..... McLauchlin J, Little C and BC Hobbs Hobbs' food poisoning and food.

  10. On the stabilization of NbV-solutions by ZrIV and HfIV

    International Nuclear Information System (INIS)

    Soerensen, E.; Bjerre, A.B.

    1987-11-01

    Niobium cannot be separated from zirconium or hafnium when these elements occur together in solution with common anions such as Cl- and SO 4 --. This is ascribed to the copolymerisation of Nb v and the hydrolyzed ionic species of Zr IV v and Hf IV by which the colloidal particles are masked as Zr- and Hf-compounds. In HCl the particles are positively charged as opposed to when they are in sulphate solution where the Zr- and Hf- sulphate complexes confer a negative charge. The two cases are considered separately. (author)

  11. Synthesis and evaluation of artificial antigens for astragaloside IV

    Directory of Open Access Journals (Sweden)

    Sheng-lan Yu

    Full Text Available The objective of this study was to produce artificial antigens for astragaloside IV that could be used to prepare antibodies against astragaloside IV screened in Radix astragali (Astragalus membranaceus (Fisch Bunge, Fabaceae and its preparations, using an indirect ELISA. Astragaloside IV was coupled to carrier proteins, bovine serum albumin and ovalbumin using the sodium periodate method and was then evaluated using SDS-PAGE, MALDI-TOF MS and animal immunizations. The coupling ratio of astragaloside IV to bovine serum albumin ratio was determined to be thirteen, and the indirect ELISA demonstrated that three groups of mice immunized with astragaloside IV-bovine serum albumin produced anti-astragaloside IV- bovine serum albumin-specific antibody, with a minimum serum titer of 1:9600. A method for synthesizing highly immunogenic astragaloside IV artificial antigens was successfully developed thus indicating its feasibility in the establishment of a fast immunoassay for astragaloside IV content determination in Radix astragali and its products.

  12. A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

    DEFF Research Database (Denmark)

    Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

    2017-01-01

    transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

  13. ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

    Directory of Open Access Journals (Sweden)

    Tina Zimmermann

    2016-10-01

    Full Text Available Huntington's disease (HD is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor. By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA chemical and two genetic HD mouse models (R6/2 and N171-82Q on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by BDNF neural progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed only minor improvements. Tumor formation was absent, and regeneration was attributed to enhanced neuronal and striatal differentiation. In addition, adult neurogenesis was preserved in a BDNF-dependent manner. Our findings provide significant insight for establishing therapeutic strategies for HD to ameliorate neurodegenerative symptoms.

  14. Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

    Science.gov (United States)

    Reininghaus, Eva; Reininghaus, Bernd; Fitz, Werner; Hecht, Karen; Bonelli, Raphael Maria

    2012-08-01

    Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant differences in both patient groups, displaying higher sexual desire and activity in HD patients, but MS patients also reported fewer sexual problems compared to the norming values. Conversely, the MS patients' relationships seemed to be stable despite subjectively perceived lower initiative on sexual activities. The results are discussed under the possible influences of the underlying organic changes and the psychosocial consequences of chronic progressive disorders.

  15. Machiavelli’den Hobbes’a Rönesans Dönemi Siyaset Teorisinde İnsan Doğası ve Toplum Anlayışı / The Human Nature and the Notion of Society in Renaissance Political Theory: From Machiavelli to Hobbes

    Directory of Open Access Journals (Sweden)

    Olkan SENEMOĞLU

    2016-07-01

    Full Text Available Bu çalışma Machiavelli’den başlayıp Hobbes’a kadar uzanan süreçte insan doğası ve toplum anlayışının nasıl ele alındığına ve bu anlayışın düşünürlerin kendi sistemlerindeki yerine odaklanmaktadır. Fakat çalışmada Yunan düşünürler Platon ve Aristoteles›ten başlayıp, Doğu düşünürleri Farabi ve İbn-i Sina’ya kadar insan doğası ve toplum tartışmalarına da yer verilmiştir. Böylece ele alınan dönemle, öncesinin kısa bir karşılaştırması yapılırken bu dönemin ayırıcı özelliği de gösterilmeye çalışılmaktadır. İnsan doğası tartışması düşünürler için kendi sistemlerini oluşturmada kilit rol oynamaktadır. Bundan dolayı Machiavelli, insanın açgözlü, çıkarcı olduğunu düşündüğü için yöneticiye dikkatli olması gerektiğini söylediği gibi, Hobbes, insanın doğası gereği kendi çıkarını düşünmeye yöneldiğini ve insanın insanla süren sonsuz bir savaşım içinde olduğunu düşündüğü için bu savaş halini bir barış hali olarak tesis edecek bir egemenlik sistemi geliştirmektedir. Diğer taraftan, düşünürlerin insan doğası tartışmaları, insanın diğer varlıklardan hangi yönüyle farklılaştığına dikkat çekerken, toplumun oluşma nedeni de yine insanın doğası gereği duyduğu gereksinimler veya doğasındaki eksiklikler itibariyle var olabileceğine odaklanmıştır. / This study focuses on how the human nature and the the notion of society were evaluated during the period starting from Machiavelli to Hobbes and the position of such an understanding within the system of these philosophers. However, the article also considers the discussions on human nature and society including the Greek philosophers from Plato and Aristoteles to Eastern philosophers, such as Farabi and Avicenna. Thus, a comparison of the previous era and the subject matter has ben established. The discussions around the human nature have a principal

  16. Market opportunities: U.S. - PADD IV

    International Nuclear Information System (INIS)

    Garner, R.P.

    1997-01-01

    The current supply and demand balance, the short and long term expectations and marketing opportunities for Canadian crude oil in PADD IV, the Rocky Mountain region in the US, were reviewed. It was suggested that market opportunities in PADD IV are derived from the following four factors: (1) crude oil declines within that area, (2) federal regulations, (3) competitive presence with markets, and (4) population growth. The overall conclusion was that Canadian producers and PADD IV refiners will be looking at an ever-growing relationship based on freight equalized world crude prices. 8 tabs., 5 figs

  17. Report for 2011 from the Bordeaux IVS Analysis Center

    Science.gov (United States)

    Charlot, Patrick; Bellanger, Antoine; Bourda, Geraldine; Collioud, Arnaud; Baudry, Alain

    2012-01-01

    This report summarizes the activities of the Bordeaux IVS Analysis Center during the year 2011. The work focused on (i) regular analysis of the IVS-R1 and IVS-R4 sessions with the GINS software package; (ii) systematic VLBI imaging of the RDV sessions and calculation of the corresponding source structure index and compactness values; (iii) imaging of the sources observed during the 2009 International Year of Astronomy IVS observing session; and (iv) continuation of our VLBI observational program to identify optically-bright radio sources suitable for the link with the future Gaia frame. Also of importance is the enhancement of the IVS LiveWeb site which now comprises all IVS sessions back to 2003, allowing one to search past observations for session-specific information (e.g. sources or stations).

  18. Direct Bandgap Group IV Materials

    Science.gov (United States)

    2016-01-21

    AFRL-AFOSR-JP-TR-2017-0049 Direct Bandgap group IV Materials Hung Hsiang Cheng NATIONAL TAIWAN UNIVERSITY Final Report 01/21/2016 DISTRIBUTION A...NAME(S) AND ADDRESS(ES) NATIONAL TAIWAN UNIVERSITY 1 ROOSEVELT RD. SEC. 4 TAIPEI CITY, 10617 TW 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...14. ABSTRACT Direct bandgap group IV materials have been long sought for in both academia and industry for the implementation of photonic devices

  19. Free-format RPG IV

    CERN Document Server

    Martin, Jim

    2013-01-01

    This how-to guide offers a concise and thorough introduction to the increased productivity, better readability, and easier program maintenance that comes with the free-format style of programming in RPG IV. Although free-format information is available in IBM manuals, it is not separated from everything else, thereby requiring hours of tedious research to track down the information needed. This book provides everything one needs to know to write RPG IV in the free-format style, and author Jim Martin not only teaches rules and syntax but also explains how this new style of coding has the pot

  20. Preparation of some complexes of Th(IV) and U(IV) with tetradentate Schiff bases. The crystal structure of bis(N,N'-ethylenebis(3-methoxysalicylaldiminato)) thorium(IV) monopyridine

    Energy Technology Data Exchange (ETDEWEB)

    Hill, R J; Rickard, C E.F.; White, H E [Auckland Univ. (New Zealand). Dept. of Chemistry

    1981-01-01

    Complexes of Th(IV) and U(IV) with tetradentate Schiff bases derived from substituted salicylaldehydes have been prepared and characterised. The structure of bis(N,N'-ethylenebis(3-methoxysalicylaldiminato)) Th(IV) monopyridine has been determined by X-ray crystallographic methods. The crystals are triclinic, a = 13.468, b = 9.932, c = 16.552 A, ..cap alpha.. = 91.74, ..beta.. = 94.69, ..gamma.. = 93.03/sup 0/, space group P/sub 1//sup -/. The molecules are eight coordinate with a slightly distorted dodecahedral geometry with the imine nitrogen atoms in the dodecahedral A sites. The pyridine molecule is uncoordinated and functions in a space-filling role.

  1. 78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption...

    Science.gov (United States)

    2013-04-10

    ... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P. and DeltaPoint...

  2. Algunas Notas sobre Domingo de Soto y la Prehistoria del Estado de Naturaleza Hobbesiano || Some notes about Domingo de Soto and the prehistory of Hobbe’s state of nature

    Directory of Open Access Journals (Sweden)

    David Jiménez Castaño

    2015-06-01

    Full Text Available RESUMEN: El objetivo de este breve trabajo es mostrar algunas relaciones que pueden ser trazadas entre las teorías políticas del teólogo español Domingo de Soto y el filósofo inglés Thomas Hobbes. De hecho, lo que intentamos probar es que el concepto de dominio de Soto y sus opiniones sobre el estado del hombre después de la Caída tienen cierta presencia en el estado de naturaleza que Hobbes usa para demostrar la necesidad del Estado. ABSTRACT: The aim of this brief work is to show some relations that can be drawn between the political theories of the Spanish theologian Domingo de Soto and the English philosopher Thomas Hobbes. In fact, what we want to prove is that Soto’s concept of dominion and his opinions about the state of man after the fall have some presence in the state of nature that Hobbes uses to demonstrate the necessity of the State.

  3. Dipeptidyl peptidase IV inhibitory activity of protein hydrolyzates ...

    African Journals Online (AJOL)

    Background: Type 2 diabetes is a chronic metabolic disorder. Recently, dipeptidyl peptidase IV (DPP-IV) inhibitors that protect incretin hormones from being cleaved by DPP-IV have been used as drugs to control glycemia. This study examined the potential hypoglycemic effect of amaranth grain storage protein hydrolyzates ...

  4. Molecular diagnosis of Huntington disease in Brazilian patients Diagnóstico molecular da doença de Huntington em pacientes brasileiros

    Directory of Open Access Journals (Sweden)

    TEREZA C. LIMA E SILVA

    2000-03-01

    Full Text Available Huntington disease (HD is a progressive neurodegenerative disorder with autosomal dominant inheritance, characterized by choreiform movements and cognitive impairment. Onset of symptoms is around 40 years of age and progression to death occurs in approximately 10 to 15 years from the time of disease onset. HD is associated with an unstable CAG repeat expansion at the 5' and of the IT15 gene. We have genotyped the CAG repeat in the IT15 gene in 44 Brazilian individuals (42 patients and 2 unaffected family members belonging to 34 unrelated families thought to segregate HD. We found one expanded CAG allele in 32 individuals (76% belonging to 25 unrelated families. In these HD patients, expanded alleles varied from 43 to 73 CAG units and normal alleles varied from 18 to 26 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r=0.6; p=0.0001; however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2=0.4. In addition, we genotyped 25 unrelated control individuals (total of 50 alleles and found normal CAG repeats varying from 16 to 33 units. The percentage of heterozigocity of the normal allele in the control population was 88%. In conclusion, our results showed that not all patients with the "HD" phenotype carried the expansion at the IT15 gene. Furthermore, molecular diagnosis was possible in all individuals, since no alleles of intermediate size were found. Therefore, molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling.A doença de Huntington (HD é afecção neurodegenerativa com padrão de herança autossômica dominante caracterizada por movimentos involuntários coreiformes e alterações cognitivas. O início dos sintomas ocorre em torno dos 40 de idade, progredindo até a morte em um período de aproximadamente 10 a 15 anos ap

  5. Astragaloside IV liposomes ameliorates adriamycin-induced ...

    African Journals Online (AJOL)

    Methods: The rats were given a single tail intravenous injection of adriamycin (6 mg/kg) within 1 week, and then divided into four groups including normal, model, benazepril and astragaloside IV liposomes group. They were all orally administered dosage of benazepril and astragaloside IV liposomes once daily for 8 weeks.

  6. Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases.

    Science.gov (United States)

    Van Liew, Charles; Santoro, Maya S; Goldstein, Jody; Gluhm, Shea; Gilbert, Paul E; Corey-Bloom, Jody

    2016-12-01

    We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles. © The Author(s) 2016.

  7. LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington's Disease.

    Science.gov (United States)

    Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Paganetti, Paolo; Kuhn, Rainer; Young, Anne B; Kazantsev, Aleksey G; Hersch, Steven

    2016-12-15

    Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington's disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates.

  8. High cost of stage IV pressure ulcers.

    Science.gov (United States)

    Brem, Harold; Maggi, Jason; Nierman, David; Rolnitzky, Linda; Bell, David; Rennert, Robert; Golinko, Michael; Yan, Alan; Lyder, Courtney; Vladeck, Bruce

    2010-10-01

    The aim of this study was to calculate and analyze the cost of treatment for stage IV pressure ulcers. A retrospective chart analysis of patients with stage IV pressure ulcers was conducted. Hospital records and treatment outcomes of these patients were followed up for a maximum of 29 months and analyzed. Costs directly related to the treatment of pressure ulcers and their associated complications were calculated. Nineteen patients with stage IV pressure ulcers (11 hospital-acquired and 8 community-acquired) were identified and their charts were reviewed. The average hospital treatment cost associated with stage IV pressure ulcers and related complications was $129,248 for hospital-acquired ulcers during 1 admission, and $124,327 for community-acquired ulcers over an average of 4 admissions. The costs incurred from stage IV pressure ulcers are much greater than previously estimated. Halting the progression of early stage pressure ulcers has the potential to eradicate enormous pain and suffering, save thousands of lives, and reduce health care expenditures by millions of dollars. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci.

    Science.gov (United States)

    Baine, Fiona K; Peerbhai, Nabeelah; Krause, Amanda

    2018-07-15

    Huntington disease (HD) is a progressive neurodegenerative disease, characterised by a triad of movement disorder, emotional and behavioural disturbances and cognitive impairment. The underlying cause is an expanded CAG repeat in the huntingtin gene. For a small proportion of patients presenting with HD-like symptoms, the mutation in this gene is not identified and they are said to have a HD "phenocopy". South Africa has the highest number of recorded cases of an African-specific phenocopy, Huntington disease-like 2 (HDL2), caused by a repeat expansion in the junctophilin-3 gene. However, a significant proportion of black patients with clinical symptoms suggestive of HD still test negative for HD and HDL2. This study thus aimed to investigate five other loci associated with HD phenocopy syndromes - ATN1, ATXN2, ATXN7, TBP and C9orf72. In a sample of patients in whom HD and HDL2 had been excluded, a single expansion was identified in the ATXN2 gene, confirming a diagnosis of Spinocerebellar ataxia 2. The results indicate that common repeat expansion disorders do not contribute significantly to the HD-like phenotype in black South African patients. Importantly, allele sizing reveals unique distributions of normal repeat lengths across the associated loci in the African population studied. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. The challenge of juvenile Huntington disease: to test or not to test.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

    2013-03-12

    In a cohort of patients with suspected juvenile-onset Huntington disease (HD), we compared HD expansion-positive and -negative cases in order to identify parameters that may allow differentiating between them and may act as a guide to clinicians contemplating genetic testing. We analyzed the clinical and genetic characteristics of 76 juvenile-onset patients referred consecutively for HD genetic testing over a 16-year period. In total, 24 patients were positive for the HD expansion (7.8% of our HD cohort). Mean age at onset of expanded cases was similar to unexpanded cases. All expanded cases had a family history of genetically confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000). Clinical symptoms at onset or at presentation could not differentiate between expanded and unexpanded patients. Although criteria suggested by previous reports allowed statistical differentiation between the 2 groups, they were not sufficiently sensitive and specific to be used in clinical context and performed less satisfactorily than presence of a family history of HD alone. A diagnosis of juvenile HD should be primarily contemplated in symptomatic children with a family history of HD, although a proportion of these will test negative. With no family history of HD, juvenile HD is very unlikely and genetic testing should never delay searching for other causes. The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test.

  11. An electrophysiological analysis of altered cognitive functions in Huntington disease.

    Science.gov (United States)

    Münte, T F; Ridao-Alonso, M E; Preinfalk, J; Jung, A; Wieringa, B M; Matzke, M; Dengler, R; Johannes, S

    1997-09-01

    Neuropsychological deficits are a main feature of Huntington disease (HD) with previous data suggesting involvement of memory functions and visual processing. To increase the knowledge about cognitive malfunction in HD in the domains of visual processing and memory by the use of modern electrophysiological techniques (event-related potentials [ERPs]). A case-control design was used. Three ERP paradigms were used; a parallel visual search paradigm allowed for the simultaneous processing of a multi-element visual array in search of a target stimulus, while a serial search paradigm with varied numbers of distractor items necessitated a serial one by one scanning of the arrays. The third experiment was a word-recognition memory task. The measurements were obtained in a neurophysiological laboratory of a university hospital. Nine patients with HD and 9 control subjects matched for age, sex, and education were studied. Components of averaged ERPs were quantified by latency and amplitude measures and subjected to statistical analysis. Behavioral measures (search time, hit rate, and recognition accuracy) were assessed as well. The early visual components showed a significant latency shift (delay of about 50 milliseconds) in HD. In the search paradigms the P3 components differentiating target and standard stimuli were virtually absent in HD as was the ERP effect indexing word recognition. This was accompanied by a marked delay in search times and lower hit rates in the search tasks and a grossly reduced recognition accuracy in the memory task. The results suggest marked impairments of patients with HD in early visual sensory processing (early components). Deficits in visual search might be attributed to an impairment to deploy attentional resources across the visual field and/or an inability to control eye movements. The ERPs in the memory task differed grossly from similar data obtained by others in patients with Alzheimer disease, suggesting a different neural basis for

  12. β-Defensin genomic copy number does not influence the age of onset in Huntington's Disease.

    Science.gov (United States)

    Vittori, Angelica; Orth, Michael; Roos, Raymund A C; Outeiro, Tiago F; Giorgini, Flaviano; Hollox, Edward J

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

  13. Echolalia or functional repetition in conversation--a case study of an individual with Huntington's disease.

    Science.gov (United States)

    Saldert, Charlotta; Hartelius, Lena

    2011-01-01

    In this case study, we investigated the use of repetition in an individual with a neurogenic communication disorder. We present an analysis of interaction in natural conversations between a woman with advanced Huntington's disease (HD), whose speech had been described as sometimes characterised by echolalia, and her personal assistant. The conversational interaction is analysed on a sequential level, and recurrent patterns are explored. Although the ability of the person with HD to interact is affected by chorea, word retrieval problems and reduced comprehension, she takes an active part in conversation. The conversational partner's contributions are often adapted to her communicative ability as they are formulated as questions or suggestions that can be elaborated on or responded to with a simple 'yes' or 'no'. The person with HD often repeats the words of her conversational partner in a way that extends her contributions and shows listenership, and this use of repetition is also frequent in ordinary conversations between non-brain-damaged individuals. The results show that the conversation partners in this case cooperate in making the conversation proceed and evolve, and that verbal repetition is used in a way that works as a strategy for compensating for the impairment.

  14. Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

    Science.gov (United States)

    Minnig, Shawn; Bragg, Robert M; Tiwana, Hardeep S; Solem, Wes T; Hovander, William S; Vik, Eva-Mari S; Hamilton, Madeline; Legg, Samuel R W; Shuttleworth, Dominic D; Coffey, Sydney R; Cantle, Jeffrey P; Carroll, Jeffrey B

    2018-02-02

    Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built, open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) to test Htt Q111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, Htt Q111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, demonstrating the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.

  15. Painlevé IV coherent states

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, David, E-mail: david.bermudez@weizmann.ac.il [Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100 (Israel); Departamento de Física, Cinvestav, A.P. 14-740, 07000 México D.F. (Mexico); Contreras-Astorga, Alonso, E-mail: aloncont@iun.edu [Department of Mathematics and Actuarial Science, Indiana University Northwest, 3400 Broadway, Gary IN 46408 (United States); Departamento de Física, Cinvestav, A.P. 14-740, 07000 México D.F. (Mexico); Fernández C, David J., E-mail: david@fis.cinvestav.mx [Departamento de Física, Cinvestav, A.P. 14-740, 07000 México D.F. (Mexico)

    2014-11-15

    A simple way to find solutions of the Painlevé IV equation is by identifying Hamiltonian systems with third-order differential ladder operators. Some of these systems can be obtained by applying supersymmetric quantum mechanics (SUSY QM) to the harmonic oscillator. In this work, we will construct families of coherent states for such subset of SUSY partner Hamiltonians which are connected with the Painlevé IV equation. First, these coherent states are built up as eigenstates of the annihilation operator, then as displaced versions of the extremal states, both involving the related third-order ladder operators, and finally as extremal states which are also displaced but now using the so called linearized ladder operators. To each SUSY partner Hamiltonian corresponds two families of coherent states: one inside the infinite subspace associated with the isospectral part of the spectrum and another one in the finite subspace generated by the states created through the SUSY technique. - Highlights: • We use SUSY QM to obtain Hamiltonians with third-order differential ladder operators. • We show that these systems are related with the Painlevé IV equation. • We apply different definitions of coherent states to these Hamiltonians using the third-order ladder operators and some linearized ones. • We construct families of coherent states for such systems, which we called Painlevé IV coherent states.

  16. Painlevé IV coherent states

    International Nuclear Information System (INIS)

    Bermudez, David; Contreras-Astorga, Alonso; Fernández C, David J.

    2014-01-01

    A simple way to find solutions of the Painlevé IV equation is by identifying Hamiltonian systems with third-order differential ladder operators. Some of these systems can be obtained by applying supersymmetric quantum mechanics (SUSY QM) to the harmonic oscillator. In this work, we will construct families of coherent states for such subset of SUSY partner Hamiltonians which are connected with the Painlevé IV equation. First, these coherent states are built up as eigenstates of the annihilation operator, then as displaced versions of the extremal states, both involving the related third-order ladder operators, and finally as extremal states which are also displaced but now using the so called linearized ladder operators. To each SUSY partner Hamiltonian corresponds two families of coherent states: one inside the infinite subspace associated with the isospectral part of the spectrum and another one in the finite subspace generated by the states created through the SUSY technique. - Highlights: • We use SUSY QM to obtain Hamiltonians with third-order differential ladder operators. • We show that these systems are related with the Painlevé IV equation. • We apply different definitions of coherent states to these Hamiltonians using the third-order ladder operators and some linearized ones. • We construct families of coherent states for such systems, which we called Painlevé IV coherent states

  17. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2011-11-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

  18. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model.

    Science.gov (United States)

    Chen, Xi; Wu, Jun; Lvovskaya, Svetlana; Herndon, Emily; Supnet, Charlene; Bezprozvanny, Ilya

    2011-11-25

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs). Our group has previously demonstrated that calcium (Ca2+) signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128). Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT) MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2) and spinocerebellar ataxia 3 (SCA3) mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg) twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that RyanR inhibitors and Ca2+ signaling stabilizers such as

  19. Synthesis, characterization and thermal behaviour of cadmium (II) complexes of photosubstituted octacyano-molybdate(IV) and -tungstate(IV) with ethylenediamine

    International Nuclear Information System (INIS)

    Ali, S.I.; Majid, Kowsar

    1998-01-01

    Photosubstituted ethylenediamine complexes of M(CN) 8 4- [where M =Mo(IV) or W(IV)] with cadmium (II) chloride have been synthesized and characterized by infrared (IR), thermogravimetric (TG) and differential scanning calorimetry (DSC). Both Mo(IV) and W(IV) show similar stoichiometric as well as thermal decomposition behaviour. The assigned general formula is Cd[M(CN) 3 (OH)(C 2 H 8 N 2 ) 2 ](C 2 H 8 N 2 ) Cl 2 XH 2 O [where M = Mo(IV) for which X = 1(I) and M = W(IV) for which X = 2 (II)]. The presence of CN - , OH - and C 2 H 8 N 2 has been shown by observed characteristic IR peaks. The extra absorption bands appearing in complex (II) are due to librational modes of water which show the formation of hydrogen bonding, which is also supported by TG analysis. The loss of these absorption bands rules out this type of bonding in (I). Both the complexes decompose in three steps up to 650 degC after which there is no change. DSC of the complexes also shows three transitions, two exothermic and one endothermic. On the basis of TG and DSC thermograms, mechanism for the decomposition of each step has been shown. Kinetic parameters like activation energy (E a ), frequency factor (A) and entropy of activation (ΔS) have been calculated using different integral methods. (author)

  20. Nordic Nuclear Materials Forum for Generation IV Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Anghel, C. (Studsvik Nuclear AB, Nykoeping (Sweden)); Penttilae, S. (Technical Research Centre of Finland, VTT (Finland))

    2010-03-15

    A network for material issues for Generation IV nuclear power has been initiated within the Nordic countries. The objectives of the Generation IV Nordic Nuclear Materials Forum (NOMAGE4) are to put the basis of a sustainable forum for Gen IV issues, especially focussing on fuels, cladding, structural materials and coolant interaction. Other issues include reactor physics, dynamics and diagnostics, core and fuel design. The present report summarizes the work performed during the year 2009. The efforts made include identification of organisations involved in Gen IV issues in the Nordic countries, update of the forum website, http://www.studsvik.se/GenerationIV, and investigation of capabilities for research within the area of Gen IV. Within the NOMAGE4 project a seminar on Generation IV Nuclear Energy Systems has been organized during 15-16th of October 2009. The aim of the seminar was to provide a forum for exchange of information, discussion on future research needs and networking of experts on Generation IV reactor concepts. As an outcome of the NOMAGE4, a few collaboration project proposals have been prepared/planned in 2009. The network was welcomed by the European Commission and was mentioned as an exemplary network with representatives from industries, universities, power companies and research institutes. NOMAGE4 has been invited to participate to the 'European Energy Research Alliance, EERA, workshop for nuclear structural materials' http://www.eera-set.eu/index.php?index=41 as external observers. Future plans include a new Nordic application for continuation of NOMAGE4 network. (author)

  1. Nordic Nuclear Materials Forum for Generation IV Reactors

    International Nuclear Information System (INIS)

    Anghel, C.; Penttilae, S.

    2010-03-01

    A network for material issues for Generation IV nuclear power has been initiated within the Nordic countries. The objectives of the Generation IV Nordic Nuclear Materials Forum (NOMAGE4) are to put the basis of a sustainable forum for Gen IV issues, especially focussing on fuels, cladding, structural materials and coolant interaction. Other issues include reactor physics, dynamics and diagnostics, core and fuel design. The present report summarizes the work performed during the year 2009. The efforts made include identification of organisations involved in Gen IV issues in the Nordic countries, update of the forum website, http://www.studsvik.se/GenerationIV, and investigation of capabilities for research within the area of Gen IV. Within the NOMAGE4 project a seminar on Generation IV Nuclear Energy Systems has been organized during 15-16th of October 2009. The aim of the seminar was to provide a forum for exchange of information, discussion on future research needs and networking of experts on Generation IV reactor concepts. As an outcome of the NOMAGE4, a few collaboration project proposals have been prepared/planned in 2009. The network was welcomed by the European Commission and was mentioned as an exemplary network with representatives from industries, universities, power companies and research institutes. NOMAGE4 has been invited to participate to the 'European Energy Research Alliance, EERA, workshop for nuclear structural materials' http://www.eera-set.eu/index.php?index=41 as external observers. Future plans include a new Nordic application for continuation of NOMAGE4 network. (author)

  2. Six psychotropics for pre-symptomatic & early Alzheimer's (MCI, Parkinson's, and Huntington's disease modification

    Directory of Open Access Journals (Sweden)

    Edward C Lauterbach

    2016-01-01

    Full Text Available The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs, including Alzheimer's disease (AD, Parkinson's disease (PD, and Huntington's disease (HD, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

  3. A COMPARATIVE CLINICAL STUDY BETWEEN IV ESMOLOL AND IV FENTANYL ON ATTENUATION OF HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

    Directory of Open Access Journals (Sweden)

    Abu Lais Mustaque

    2016-04-01

    Full Text Available INTRODUCTION Laryngoscopy and intubation is an integral part for providing general anaesthesia to patients undergoing various types of surgery. It also plays an important role in critical care units viz. for providing mechanical ventilation. It is a very essential tool in the hands of anaesthesiologist in maintaining airway. The present study is undertaken to determine and compare the efficacy of single bolus dose of IV esmolol 1 mg/kg and IV fentanyl 2 mcg/kg in attenuating the haemodynamic responses to laryngoscopy and tracheal intubation and to ascertain the effectiveness of esmolol hydrochloride and fentanyl citrate in suppressing sympathetic responses. MATERIAL & METHODS The study was conducted under the Department of Anaesthesiology and Critical Care, Assam Medical College and Hospital, Dibrugarh, during the period July 2013 to June 2014. For this purpose, 150 patients of either sex between 20-50 years of ASA I & II physical status were selected after obtaining informed and written consent and were divided into two groups namely, Group E receiving IV esmolol (1 mg/kg and Group F receiving IV fentanyl (2 mcg/kg. RESULTS Inj. fentanyl 2 mcg/kg IV administered 5 minutes before laryngoscopy and intubation was able to prevent adverse haemodynamic changes better than Inj. esmolol 1 mg/kg IV administered 3 minutes prior to laryngoscopy and intubation during elective surgeries under general anaesthesia. CONCLUSION Hence, from the findings of this study we can conclude that IV bolus dose of fentanyl 2 mcg/kg administered 5 minutes before laryngoscopy and intubation can attenuate the sympathetic response to laryngoscopy and intubation without any side effects of the drug in healthy patients undergoing elective surgeries under general anaesthesia.

  4. Computations of nuclear response functions with MACK-IV

    International Nuclear Information System (INIS)

    Abdou, M.A.; Gohar, Y.

    1978-01-01

    The MACK computer program calculates energy pointwise and multigroup nuclear response functions from basic nuclear data in ENDF/B format. The new version of the program, MACK-IV, incorporates major developments and improvements aimed at maximizing the utilization of available nuclear data and ensuring energy conservation in nuclear heating calculations. A new library, MACKLIB-IV, of nuclear response functions was generated in the CTR energy group structure of 171 neutron groups and 36 gamma groups. The library was prepared using MACK-IV and ENDF/B-IV and is suitable for fusion, fusion-fission hybrids, and fission applications

  5. Computations of nuclear response functions with MACK-IV

    Energy Technology Data Exchange (ETDEWEB)

    Abdou, M A; Gohar, Y

    1978-01-01

    The MACK computer program calculates energy pointwise and multigroup nuclear response functions from basic nuclear data in ENDF/B format. The new version of the program, MACK-IV, incorporates major developments and improvements aimed at maximizing the utilization of available nuclear data and ensuring energy conservation in nuclear heating calculations. A new library, MACKLIB-IV, of nuclear response functions was generated in the CTR energy group structure of 171 neutron groups and 36 gamma groups. The library was prepared using MACK-IV and ENDF/B-IV and is suitable for fusion, fusion-fission hybrids, and fission applications.

  6. Redox behavior of Ce(IV)/Ce(III) in the presence of nitrilotriacetic acid: a surrogate study for An(IV)/An(III) redox behavior

    International Nuclear Information System (INIS)

    Suzuki, Y.; Nankawa, T.; Ohnuki, T.; Francis, A.J.

    2010-01-01

    Using cyclic voltammetry, we investigated the redox behavior of Ce(IV)/Ce(III), which is a surrogate for An(IV)/An(III) (An = actinides), in a solution of nitrilotriacetic acid (NTA) at 25 C. The cyclic voltammogram of Ce in a 0.1 M NTA solution at pH 6 showed a reversible one-electron redox reaction for Ce(IV)/Ce(III) at 0.51 V vs. Ag/AgCl. This redox potential was much lower than that obtained in 1 M nitric acid, indicating that Ce(IV) was preferentially stabilized by complexation with NTA. The redox potential in the NTA solution was independent of the Ce concentration from 2 to 20 mM, NTA concentration from 5 to 200 mM and pH between 3 and 7. These results indicated that no polymerization and no additional coordination of NTA and OH to the Ce(III)-NTA complex took place during the redox reaction. As the speciation calculation of Ce(III) in the NTA solution showed that the predominant species was Ce III (nta) 2 3 (H 3 nta = NTA), the redox reaction of the Ce-NTA complex was expressed by the following: Ce IV (nta) 2 2- + e - ↔ Ce III (nta) 2 3 . The logarithm of the stability constant of Ce IV (nta) 2 2- was calculated to be 38.6 ± 0.8 for I = 0 from the redox potential shift of Ce(IV)/Ce(III) in the NTA solution. The value was in good accordance with the stability constant of the Np IV (nta) 2 2- complex, demonstrating that the aqueous coordination chemistry of Ce(IV) with NTA is quite similar to that of An(IV). These results strongly suggest that a negative shift of the Pu(IV)/Pu(III) redox potential in the NTA solution should make Pu(IV) more stable than Pu(III) even in a reducing environment. (orig.)

  7. Genetic Counselling for Predictive Testing in Huntington's Disease in One Centre since 1993. Gender-Specific Aspects of Decision-Making.

    Science.gov (United States)

    Arning, Larissa; Witt, Constantin N; Epplen, Jörg T; Stemmler, Susanne

    2015-01-01

    The discovery of the mutation causing Huntington's disease (HD) in 1993 allowed direct mutation analysis and predictive testing to identify currently unaffected carriers with a sensitivity and specificity of virtually 100%. The present study was designed to comprehensively profile the participants who sought predictive testing for HD between 1993 and 2009 in our Huntington centre. Using a retrospective design, we analysed the written documentation of the counselling sessions for all referrals for predictive mutation testing in this time span. Six hundred sixty-three individuals at risk for HD requested predictive testing. Roughly half (n = 333) completed the protocol and received their test result. In general our findings are in accordance with other reports: most participants share an a priori risk of 50% (91.1%); more females request testing (58.5%); and those who ask for the result are mostly in their 30 s (mean = 35.1 years). Of those at 50% or 25% prior risks, 47.4% and 22.7%, respectively, tested positive in accordance with the respective risk of inheriting HD. Generally, more participants with an affected mother than father sought genetic testing (52.5% versus 47.5%). Interestingly, this difference was especially evident in the group of females who finally withdrew from testing (59.1%, p = 0.040). Men, in particular those who decided in favour of the test, were more often accompanied by their partner in the pre-test counselling session than vice versa (67.9% versus 44.7%, p = 0.003). On the other hand, significantly more men who were being tested did not have a companion in the pre-test session as compared with men who decided against the test (40.0% versus 25.7%, p = 0.012). During the first four years of predictive testing (1993–1996) more participants completed the protocol and received their test result as in later years. Yet, in this early time span significantly fewer females finally decided in favour of the test (48.4%, p = 0.005). These findings

  8. Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

    Directory of Open Access Journals (Sweden)

    Jack C. Reidling

    2018-01-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

  9. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Piotr Hadaczek

    2016-01-01

    Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

  10. Safety assessment for Generation IV nuclear systems

    International Nuclear Information System (INIS)

    Leahy, T.J.

    2012-01-01

    The Generation IV International Forum (GIF) Risk and Safety Working Group (RSWG) was created to develop an effective approach for the safety of Generation IV advanced nuclear energy systems. Recent RSWG work has focused on the definition of an integrated safety assessment methodology (ISAM) for evaluating the safety of Generation IV systems. ISAM is an integrated 'tool-kit' consisting of 5 analytical techniques that are available and matched to appropriate stages of Generation IV system concept development: 1) qualitative safety features review - QSR, 2) phenomena identification and ranking table - PIRT, 3) objective provision tree - OPT, 4) deterministic and phenomenological analyses - DPA, and 5) probabilistic safety analysis - PSA. The integrated methodology is intended to yield safety-related insights that help actively drive the evolving design throughout the technology development cycle, potentially resulting in enhanced safety, reduced costs, and shortened development time

  11. An examination of the nexus between Thomas Hobbes‟ concept of ...

    African Journals Online (AJOL)

    In order to remedy the above personality and drive of human beings, Hobbes found it imperative to propound a theory of the state, where all will be saved through a social contract. This paper is an attempt to establish a link between Hobbes' concept of human nature and his theory of the state. We articulate that it was the ...

  12. U(IV) fluorescence spectroscopy. A new speciation tool

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, Susanne; Brendler, Vinzenz [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes; Steudtner, Robin [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Inst. of Resource Ecology

    2017-06-01

    We combined absorption and fluorescence spectroscopy to study the speciation of U(IV) in solution in concentrations down to 10{sup -6} M uranium. With our time-resolved laser-induced fluorescence setup we could determine the fluorescence decay time of U(IV) in perchloric as well as in chloric acid with 2.6 ± 0.3 ns at room temperature and 148.4 ± 6.5 ns at liquid nitrogen temperature. For the U(IV) sulfate system, we observed a bathochromic shift and a peak shape modification in the fluorescence spectra with increasing sulfate concentration in solution. Thus, the potential of U(IV) fluorescence for speciation analysis could be proven.

  13. N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease.

    Science.gov (United States)

    Wright, Dean J; Gray, Laura J; Finkelstein, David I; Crouch, Peter J; Pow, David; Pang, Terence Y; Li, Shanshan; Smith, Zoe M; Francis, Paul S; Renoir, Thibault; Hannan, Anthony J

    2016-07-15

    Glutamatergic dysfunction has been implicated in the pathogenesis of depressive disorders and Huntington's disease (HD), in which depression is the most common psychiatric symptom. Synaptic glutamate homeostasis is regulated by cystine-dependent glutamate transporters, including GLT-1 and system x c - In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine-γ-lygase, has recently been shown to be lowered. The aim of the present study was to establish whether cysteine supplementation, using N-acetylcysteine (NAC) could ameliorate glutamate pathology through the cystine-dependent transporters, system x c - and GLT-1. We demonstrate that the R6/1 transgenic mouse model of HD has lower basal levels of cystine, and showed depressive-like behaviors in the forced-swim test. Administration of NAC reversed these behaviors. This effect was blocked by co-administration of the system x c - and GLT-1 inhibitors CPG and DHK, showing that glutamate transporter activity was required for the antidepressant effects of NAC. NAC was also able to specifically increase glutamate in HD mice, in a glutamate transporter-dependent manner. These in vivo changes reflect changes in glutamate transporter protein in HD mice and human HD post-mortem tissue. Furthermore, NAC was able to rescue changes in key glutamate receptor proteins related to excitotoxicity in HD, including NMDAR2B. Thus, we have shown that baseline reductions in cysteine underlie glutamatergic dysfunction and depressive-like behavior in HD and these changes can be rescued by treatment with NAC. These findings have implications for the development of new therapeutic approaches for depressive disorders. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

    Science.gov (United States)

    Krzysztoń-Russjan, Jolanta

    2016-12-30

    Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  15. Huntington's disease: current epidemiology and pharmacological management in UK primary care.

    Science.gov (United States)

    Sackley, Catherine; Hoppitt, Thomas J; Calvert, Melanie; Gill, Paramjit; Eaton, Benjamin; Yao, Guiqing; Pall, Hardev

    2011-01-01

    Recent debate suggests Huntington's disease (HD) may be more prevalent than previously reported. In addition, relatively little is known about current disease management. This study aims to provide epidemiological data and describe the pharmacological management of HD in the United Kingdom. A primary care research database was accessed to identify incident and prevalent HD cases between January 1, 2004, and December 31, 2008. Patients with Read codes denoting a definite diagnosis or possible diagnosis, and undiagnosed patients with a positive family history were identified. A subset of patients with a definite diagnosis and prescribed medication indicating symptom onset was also identified. Epidemiological data were estimated. Pharmacological prescriptions to HD patients from 2004 to 2008 were identified, and prescription frequencies were grouped according to the British National Formulary categories. HD incidence estimates ranged from 0.44 to 0.78 per 100,000 person-years, and HD prevalence ranged from 5.96 to 6.54 per 100,000 of the population. Forty-four percent of pharmacological prescriptions targeted the central nervous system. Nearly half of the HD patients were prescribed antidepressants, and over 40% were prescribed analgesics. Although prevalence estimates fell short of figures suggested in recent debate, it is feasible that the true prevalence may be much higher than previously reported. Pharmacological management appears to rely heavily on central nervous system drugs and nutrition support. Many of these drugs are prescribed to HD patients for reasons other than the medication's primary use. Further work is required to evaluate the impact of alternative management strategies, such as therapist intervention, counselling, and organisation support, on the patients' quality of life. Copyright © 2011 S. Karger AG, Basel.

  16. A sputnik IV saga

    Science.gov (United States)

    Lundquist, Charles A.

    2009-12-01

    The Sputnik IV launch occurred on May 15, 1960. On May 19, an attempt to deorbit a 'space cabin' failed and the cabin went into a higher orbit. The orbit of the cabin was monitored and Moonwatch volunteer satellite tracking teams were alerted to watch for the vehicle demise. On September 5, 1962, several team members from Milwaukee, Wisconsin made observations starting at 4:49 a.m. of a fireball following the predicted orbit of Sputnik IV. Requests went out to report any objects found under the fireball path. An early morning police patrol in Manitowoc had noticed a metal object on a street and had moved it to the curb. Later the officers recovered the object and had it dropped off at the Milwaukee Journal. The Moonwarch team got the object and reported the situation to Moonwatch Headquarters at the Smithsonian Astrophysical Observatory. A team member flew to Cambridge with the object. It was a solid, 9.49 kg piece of steel with a slag-like layer attached to it. Subsequent analyses showed that it contained radioactive nuclei produced by cosmic ray exposure in space. The scientists at the Observatory quickly recognized that measurements of its induced radioactivity could serve as a calibration for similar measurements of recently fallen nickel-iron meteorites. Concurrently, the Observatory directorate informed government agencies that a fragment from Sputnik IV had been recovered. Coincidently, a debate in the UN Committee on Peaceful Uses of Outer Space involved the issue of liability for damage caused by falling satellite fragments. On September 12, the Observatory delivered the bulk of the fragment to the US Delegation to the UN. Two days later, the fragment was used by US Ambassador Francis Plimpton as an exhibit that the time had come to agree on liability for damage from satellite debris. He offered the Sputnik IV fragment to USSR Ambassador P.D. Morozov, who refused the offer. On October 23, Drs. Alla Massevitch and E.K. Federov of the USSR visited the

  17. Determination of uranium (IV) by flow voltammetry

    International Nuclear Information System (INIS)

    Ding Anqing

    1987-01-01

    According to the quantitative reaction of U(IV) and Fe(III) in H 2 SO 4 as well as the relation between current and concentration of substance detected, U(IV) has been determined indirectly by measurement of the electrolysis current of residual Fe(III). The columniform electrode used is made of glass carbon particles. At the range of U(IV) from a few micrograms to 40 μg, the linear relation is excellent. The relative standard deviation is within ±4%. The interference of Fe(II), Ti(IV) and U(VI) is negligible but of Ti(III) is serious. This method has been successfully applied in the determination of actual samples (both out line and on line). Main advantages of this procedure are rapid, simple, small amount of sample (only at microgram level) and easy to realize automation, able to use for on line or process analysis

  18. Testing and economical evaluation of U(IV) in Purex

    International Nuclear Information System (INIS)

    Hoisington, J.E.; Hsu, T.C.

    1983-01-01

    The use of uranous nitrate, U(IV), as a plutonium reductant in the Purex solvent extraction process could significantly reduce the waste generation at the Savannah River Plant. The current reductant is a ferrous sulfamate (FS)/hydroxylamine nitrate (HAN) mixture. The iron and sulfate in the FS are major contributors to waste generation. The U(IV) reductant oxidizes to U(VI) producing no waste. The Savannah River Laboratory has developed an efficient electrochemical cell for U(IV) production and has demonstrated the effectiveness of U(IV) as a plutonium reductant. Plant tests and economic analyses are currently being conducted to determine the cost effectiveness of U(IV) implementation. The results of recent studies are presented

  19. Are stage IV vestibular schwannomas preoperatively different from other stages?

    Science.gov (United States)

    Tringali, Stéphane; Dubreuil, Christian; Zaouche, Sandra; Ferber-Viart, Chantal

    2008-01-01

    The aim of this study was to focus on the clinical and paraclinical symptoms of patients suffering from Stage IV vestibular schwannomas (VSs). In this prospective study, we included 734 patients who have VS and candidates for operation. Patients were classified as having Stage I, II, III, or IV tumors according to Tos criteria as evaluated by magnetic resonance imaging. PREOPERATIVE CLINICAL EVALUATION: We recorded the occurrence of complaints (%) and duration (yr) of hearing loss, tinnitus, and balance disorder. Preoperative paraclinical evaluation included pure-tone (PTA) and speech audiometry, auditory brainstem response (ABR) patterns, and vestibular deficit at videonystamography (VNG). Continuous variables were compared between Stage IV and other stages using analysis of variance. Qualitative variables expressed as a percentage of presence were compared between Stage IV and other stages using percentage comparison. Quantitative Parameters. Patients with Stage IV VS were significantly younger as compared with patients with other stages. Stage IV hearing loss was greater compared with other stages at 250 and 500 Hz but smaller at 2,000 and 8,000 Hz. We found no difference in the loss of PTA between Stage IV and the other stages. Speech discriminancy score was smaller in Stage IV. The durations of hearing loss, tinnitus, and balance disorders were similar whatever the tumor stage. Auditory brainstem response patterns showed no difference in Wave III latency between Stage IV VS and other stages, whereas Wave V latency and V-I interval were higher in Stage IV. Both ABR threshold and VNG caloric deficit were higher in Stage IV VS compared with other stages. Qualitative Parameters. The percentage of patients with Stage IV was lower than that with Stages II and III. The percentage of men and women was similar in all stages. The occurrence of hearing loss was similar in all stages, whereas that of tinnitus was lower in Stage IV compared with Stages I and II. In

  20. Contratarianismo hobbesiano?

    Directory of Open Access Journals (Sweden)

    Mariana Kuhn de Oliveira

    2016-09-01

    Thomas Scanlon buscou desenvolver uma abordagem contratualista da moralidade partindo de argumentos fundados apenas em princípios que ninguém poderia razoavelmente rejeitar. Ele acreditava que a maior parte das teorias contratualistas era fundamentada apenas em acordos realizados por agentes autointeressados e queria apresentar uma versão diferente de contrato social. Ele decidiu, então, chamar contratualismo sua teoria e outras fundamentadas na razoabilidade e contratarianismo aquelas fundadas na racionalidade entendida como busca pelo autointeresse. Essa se tornou uma distinção usual e Hobbes tem sido classificado como contratarianista. A posição ocupada por Hobbes deveria, entretanto, ser examinada em detalhe. A compreensão de Hobbes da racionalidade é diferente do autointeresse. Além disso, ele liga a descoberta das leis de natureza, que comandam a reciprocidade, à razão. No entanto, o interesse na preservação da própria vida é um fim importante na teoria dele. O objetivo do presente artigo é mostrar que a teoria de Hobbes é mais interessante e complexa do que a definição do contratarianismo.

  1. COBRA-IV wire wrap data comparisons

    International Nuclear Information System (INIS)

    Donovan, T.E.; George, T.L.; Wheeler, C.L.

    1979-02-01

    Thermal hydraulic analyses of hexagonally packed wire-wrapped fuel assemblies are complicated by the induced crossflow between adjacent subchannels. The COBRA-IV computer code simultaneously solves the hydrodynamics and thermodynamics of fuel assemblies. The modifications and the results are presented which are predicted by the COBRA-IV calculation. Comparisons are made with data measured in five experimental models of a wire-wrapped fuel assembly

  2. Determination of the solubility of Np(IV), Pu(III) - (VI),Am(III) - (VI), and Te(IV), (V) hydroxo compounds in 0.5 - 14 M NaOH solutions

    Energy Technology Data Exchange (ETDEWEB)

    Delegard, C.H.

    1996-09-24

    The solubilities of Am(III), Np(IV), Pu(IV), Tc(IV), Np(V), Pu(V), Am(V), and Tc(V) hydroxo compounds were studied in 0.5 to 14 M NaOH solutions at 25{+-}2 {degrees}C. The effects of fluoride, phosphate, carbonate, oxalate, and some other organic complexing agents on the solubilities of Np(IV), Pu(IV), and TC(IV) hydroxides were investigated at 1.0 and 4.0 M NAOH. Some predictions were made on the dissolved (I.V) and (V) species present in alkali solutions.

  3. Ehlers-Danlos syndrome type IV

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2007-07-01

    Full Text Available Abstract Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS, is an inherited connective tissue disorder defined by characteristic facial features (acrogeria in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular

  4. Ehlers-Danlos syndrome type IV

    Science.gov (United States)

    Germain, Dominique P

    2007-01-01

    Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering

  5. Gen IV Materials Handbook Implementation Plan

    International Nuclear Information System (INIS)

    Rittenhouse, P.; Ren, W.

    2005-01-01

    A Gen IV Materials Handbook is being developed to provide an authoritative single source of highly qualified structural materials information and materials properties data for use in design and analyses of all Generation IV Reactor Systems. The Handbook will be responsive to the needs expressed by all of the principal government, national laboratory, and private company stakeholders of Gen IV Reactor Systems. The Gen IV Materials Handbook Implementation Plan provided here addresses the purpose, rationale, attributes, and benefits of the Handbook and will detail its content, format, quality assurance, applicability, and access. Structural materials, both metallic and ceramic, for all Gen IV reactor types currently supported by the Department of Energy (DOE) will be included in the Gen IV Materials Handbook. However, initial emphasis will be on materials for the Very High Temperature Reactor (VHTR). Descriptive information (e.g., chemical composition and applicable technical specifications and codes) will be provided for each material along with an extensive presentation of mechanical and physical property data including consideration of temperature, irradiation, environment, etc. effects on properties. Access to the Gen IV Materials Handbook will be internet-based with appropriate levels of control. Information and data in the Handbook will be configured to allow search by material classes, specific materials, specific information or property class, specific property, data parameters, and individual data points identified with materials parameters, test conditions, and data source. Details on all of these as well as proposed applicability and consideration of data quality classes are provided in the Implementation Plan. Website development for the Handbook is divided into six phases including (1) detailed product analysis and specification, (2) simulation and design, (3) implementation and testing, (4) product release, (5) project/product evaluation, and (6) product

  6. Independent Examination of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): What Does the WAIS-IV Measure?

    Science.gov (United States)

    Benson, Nicholas; Hulac, David M.; Kranzler, John H.

    2010-01-01

    Published empirical evidence for the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV) does not address some essential questions pertaining to the applied practice of intellectual assessment. In this study, the structure and cross-age invariance of the latest WAIS-IV revision were examined to (a) elucidate the nature of the constructs…

  7. Generation IV nuclear reactors: Current status and future prospects

    International Nuclear Information System (INIS)

    Locatelli, Giorgio; Mancini, Mauro; Todeschini, Nicola

    2013-01-01

    Generation IV nuclear power plants (GEN IV NPPs) are supposed to become, in many countries, an important source of base load power in the middle–long term (2030–2050). Nowadays there are many designs of these NPPs but for political, strategic and economic reasons only few of them will be deployed. International literature proposes many papers and reports dealing with GEN IV NPPs, but there is an evident difference in the types and structures of the information and a general unbiased overview is missing. This paper fills the gap, presenting the state-of-the-art for GEN IV NPPs technologies (VHTR, SFR, SCWR, GFR, LFR and MSR) providing a comprehensive literature review of the different designs, discussing the major R and D challenges and comparing them with other advanced technologies available for the middle- and long-term energy market. The result of this research shows that the possible applications for GEN IV technologies are wider than current NPPs. The economics of some GEN IV NPPs is similar to actual NPPs but the “carbon cost” for fossil-fired power plants would increase the relative valuation. However, GEN IV NPPs still require substantial R and D effort, preventing short-term commercial adoption. - Highlights: • Generation IV reactors are the middle–long term technology for nuclear energy. • This paper provides an overview and a taxonomy for the designs under consideration. • R and D efforts are in the material, heat exchangers, power conversion unit and fuel. • The life cycle costs are competitive with other innovative technologies. • The hydrogen economy will foster the development of Generation IV reactors

  8. IVS Organization

    Science.gov (United States)

    2004-01-01

    International VLBI Service (IVS) is an international collaboration of organizations which operate or support Very Long Baseline Interferometry (VLBI) components. The goals are: To provide a service to support geodetic, geophysical and astrometric research and operational activities. To promote research and development activities in all aspects of the geodetic and astrometric VLBI technique. To interact with the community of users of VLBI products and to integrate VLBI into a global Earth observing system.

  9. Independent examination of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): what does the WAIS-IV measure?

    Science.gov (United States)

    Benson, Nicholas; Hulac, David M; Kranzler, John H

    2010-03-01

    Published empirical evidence for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) does not address some essential questions pertaining to the applied practice of intellectual assessment. In this study, the structure and cross-age invariance of the latest WAIS-IV revision were examined to (a) elucidate the nature of the constructs measured and (b) determine whether the same constructs are measured across ages. Results suggest that a Cattell-Horn-Carroll (CHC)-inspired structure provides a better description of test performance than the published scoring structure does. Broad CHC abilities measured by the WAIS-IV include crystallized ability (Gc), fluid reasoning (Gf), visual processing (Gv), short-term memory (Gsm), and processing speed (Gs), although some of these abilities are measured more comprehensively than are others. Additionally, the WAIS-IV provides a measure of quantitative reasoning (QR). Results also suggest a lack of cross-age invariance resulting from age-related differences in factor loadings. Formulas for calculating CHC indexes and suggestions for interpretation are provided. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  10. Industrial Waste Landfill IV upgrade package

    International Nuclear Information System (INIS)

    1994-01-01

    The Y-12 Plant, K-25 Site, and ORNL are managed by DOE's Operating Contractor (OC), Martin Marietta Energy Systems, Inc. (Energy Systems) for DOE. Operation associated with the facilities by the Operating Contractor and subcontractors, DOE contractors and the DOE Federal Building result in the generation of industrial solid wastes as well as construction/demolition wastes. Due to the waste streams mentioned, the Y-12 Industrial Waste Landfill IV (IWLF-IV) was developed for the disposal of solid industrial waste in accordance to Rule 1200-1-7, Regulations Governing Solid Waste Processing and Disposal in Tennessee. This revised operating document is a part of a request for modification to the existing Y-12 IWLF-IV to comply with revised regulation (Rule Chapters 1200-1-7-.01 through 1200-1-7-.08) in order to provide future disposal space for the ORR, Subcontractors, and the DOE Federal Building. This revised operating manual also reflects approved modifications that have been made over the years since the original landfill permit approval. The drawings referred to in this manual are included in Drawings section of the package. IWLF-IV is a Tennessee Department of Environmental and Conservation/Division of Solid Waste Management (TDEC/DSWM) Class 11 disposal unit

  11. IVS: Current Status and Future Plans

    Science.gov (United States)

    Behrend, D.; Nothnagel, A.; Petrachenko, W. T.; Tuccari, G.

    2016-12-01

    The International VLBI Service for Geodesy and Astrometry (IVS) is a globally operating service that coordinates and performs Very Long Baseline Interferometry (VLBI) activities through its constituent components. The VLBI activities are associated with the creation, provision, dissemination, and archiving of relevant VLBI data and products. The products mostly pertain to the determination of the celestial and terrestrial reference frames, the Earth orientation parameters (EOP), atmospheric parameters as well as other ancillary parameters. The IVS observational network currently consists of about 40 radio telescopes worldwide. Subsets of these telescopes (8-12 stations) participate in 24-hour observing sessions that are run several times per week and in 1-hour intensive sessions for UT1 determination every day. The current VLBI network was developed mainly in the 1970s and 1980s. A number of factors, including aging infrastructure and demanding new scientific requirements, started to challenge its future sustainability and relevance. In response, the IVS and other groups developed and started implementing the next generation VLBI system, called VGOS (VLBI Global Observing System), at existing and new sites. The VGOS network is expected to reach maturity in the early 2020s. We describe the current status, progress, and anticipated prospects of geodetic/astrometric VLBI and the IVS.

  12. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Science.gov (United States)

    Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Panigrahi, Gagan B; Hou, Caixia; Holloway, Kim; Gillis, Tammy; Guide, Jolene R; Cohen, Paula E; Li, Guo-Min; Pearson, Christopher E; Daly, Mark J; Wheeler, Vanessa C

    2013-10-01

    The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1

  13. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  14. Zirconium (IV) complexes with some polymethylenediimines | Na ...

    African Journals Online (AJOL)

    The syntheses of zirconium (IV) complexes have been carried out by the reaction of oxozirconium (IV) chloride with the appropriate diimines (Schiff bases). The complexes were isolated as yellow solids which are stable to heat. The complexes were found to be insoluble in most solvents. The infrared spectra, elemental ...

  15. PREVALENCIA Y MORTALIDAD DE LA ENFERMEDAD DE HUNTINGTON A PARTIR DEL REGISTRO POBLACIONAL DE ENFERMEDADES RARAS DE LAS ISLAS BALEARES DURANTE EL PERÍODO 2010-2013

    Directory of Open Access Journals (Sweden)

    Mercedes Cáffaro Rovira

    2017-01-01

    Full Text Available La enfermedad de Huntington (EH es una enfermedad hereditaria de baja prevalencia, por lo que se incluye en los registros de enfermedades raras. El registro poblacional de enfermedades raras de las Islas Baleares se inició en el año 2010. Previamente no existían datos de prevalencia y mortalidad de la EH en las Islas Baleares. El objetivo de este estudio fue determinar la prevalencia y la mortalidad de la enfermedad de Huntington en las Islas Baleares durante el periodo 2010-2013. Métodos: Se utilizaron como fuentes de información el registro poblacional de enfermedades raras de las Islas Baleares, del que se obtuvieron los casos diagnosticados, el Registro de mortalidad de las Islas Baleares, del que se obtuvieron los casos fallecidos, el registro del Servicio de Salud de las Islas Baleares del que se obtuvieron el número de tarjetas sanitarias y del Instituto Nacional de Estadística se obtuvieron los datos de población. Se calcularon las tasas de prevalencia y de mortalidad. Resultados: El registro poblacional de enfermedades raras de las Islas Baleares durante el periodo 2010-2013 registró 27 casos de EH. El 63% fueron mujeres. La tasa de prevalencia fue de 2,6 por 105 y la tasa de mortalidad de 1,1 por 105. La isla de Menorca fue la más afectada con una prevalencia de 5,9 por 105 y una mortalidad de 2,1 por 105. Conclusiones: La prevalencia y mortalidad de la EH en las Islas Baleares son bajas en comparación con zonas del entorno.

  16. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

    Science.gov (United States)

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

    2017-02-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. Copyright © 2017 by the Genetics Society of America.

  17. Development of Electromagnetic Analysis Model for IV-CEAPI

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jinseok; Jang, Yongtae; Lee, Myounggoo; Cho, Yeonho; Kim, Hyunmin [KEPCO Engineering and Construction, Inc., Daejeon (Korea, Republic of); Hong, Hoonbin; Baek, Minho [Woojin Inc., Osan (Korea, Republic of)

    2016-05-15

    There are many different types of position indicators such as reed switch type, ultrasonic type, solenoid type, etc. Through an analysis of strengths and weakness of those types, solenoid type was selected for an IV-CEAPI. Although solenoid type CEAPIs have been used world-wide, the IV-CEAPI is to be very different from the conventional designs due to its harsh operating environment. The concept of the IV-CEAPI is simple as shown in Figure 1. The coil is made of mineral insulated wire to be able to operate inside reactor vessel. The CEA is connected to the shaft which is made of ferromagnetic material. As the CEA position varies, the inductance variation is detected by the inductance meter located outside the vessel. Unlike the conventional ones, the IV-CEAPI used only one coil to eliminate coil connection point and electric components inside vessel. A finite element model was developed to calculate inductance of the solenoid type IV-CEAPI. The model considers eddy current effect to calculate frequency dependent inductance value. Analyses were performed to produce an inductance curve to the shaft position.

  18. Development of Electromagnetic Analysis Model for IV-CEAPI

    International Nuclear Information System (INIS)

    Park, Jinseok; Jang, Yongtae; Lee, Myounggoo; Cho, Yeonho; Kim, Hyunmin; Hong, Hoonbin; Baek, Minho

    2016-01-01

    There are many different types of position indicators such as reed switch type, ultrasonic type, solenoid type, etc. Through an analysis of strengths and weakness of those types, solenoid type was selected for an IV-CEAPI. Although solenoid type CEAPIs have been used world-wide, the IV-CEAPI is to be very different from the conventional designs due to its harsh operating environment. The concept of the IV-CEAPI is simple as shown in Figure 1. The coil is made of mineral insulated wire to be able to operate inside reactor vessel. The CEA is connected to the shaft which is made of ferromagnetic material. As the CEA position varies, the inductance variation is detected by the inductance meter located outside the vessel. Unlike the conventional ones, the IV-CEAPI used only one coil to eliminate coil connection point and electric components inside vessel. A finite element model was developed to calculate inductance of the solenoid type IV-CEAPI. The model considers eddy current effect to calculate frequency dependent inductance value. Analyses were performed to produce an inductance curve to the shaft position

  19. The affinity plutonium(IV) for nitrogen donor ligands

    International Nuclear Information System (INIS)

    Jarvis, N.V.; Hancock, R.D.

    1994-01-01

    Established ligand design principles are used to predict the solution chemistry of Pu(IV) with nitrogen donor ligands which do not contain carboxylate donors. pK a 's of the nitrogen donors are lowered by addition of hydroxyalkyl groups causing Pu(IV) to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N'N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N',N'-tetrakis(2-hydroxyethyl)-1,2-diaminoethane; N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with Pu(IV) showed that Pu(IV) has a considerable aqueous solution chemistry with these ligands. Data were processed by the ESTA library of programs and stability constants for all the systems are reported. Implications for selective ligand design for Pu(IV) are discussed. (orig.)

  20. NNDSS - Table IV. Tuberculosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table IV. Tuberculosis - 2016.This Table includes total number of cases reported in the United States, by region and by states, in accordance with the...