Le droit français et la recherche biomédicale : l'épreuve de la pratique

Exception notable au principe de l'inviolabilité de la personne, la recherche biomédicale chez l'Homme est depuis la loi du 20 décembre 1988 une réalité scientifique, médicale, voire économique pleinement reconnue par le droit français. Le choix législatif, confirmé par les modalités de sa mise en oeuvre, aura été pour mieux assurer la protection des personnes, d'englober toutes les recherches biomédicales dans la loi, les soumettant à un régime d'organisation fait de règles communes et spécifiques. La loi distingue en effet deux grands types de recherche : celles qui procurent un bénéfice individuel direct et celles sans bénéfice individuel direct. Dans la première situation, la conjonction de l'intérêt individuel et de l'intérêt collectif permet, tout en précisant rigoureusement les modalités de cette recherche, d'en admettre une pratique étendue, aux confins voire en continuité de l'activité strictement médicale. Dans la seconde des situations, au contraire, son domaine sera plus strictement limité et les obligations de ceux qui la mettent en oeuvre seront plus grandes. Il en est notamment ainsi de la mission des comités de protection des personnes, dont l'avis est obligatoire avant toute recherche, et du pouvoir des autorités sanitaires tant sur le plan de la prévention que sur celui des contrôles et des sanctions éventuelles. L'enjeu est dès lors grand pour le droit: ayant « sacrifié » le caractère absolu du principe d'inviolabilité de la personne, il doit dès lors démontrer son efficacité « au quotidien ».One notable exception to the principle involving the inviolate nature of the person occurs in biomedical research performed on humans as set forth under the Statute of December 20, 1988, raised thereby to a scientific, medical and albeit economic reality fully recognized under French law. This legislative choice, as confirmed under the conditions of its implementation, was intended to better ensure the protection of people and extend to all biomedical research within a legal cadre, thereby subjecting it to common and specific rules in an organized framework. Indeed, the law recognizes two major categories of research : one providing direct individual benefits and the other not providing them. In the first case, the coming together of individual and collective interests gives rise to the allowing of extended practive even to the limits of or in the pursuit of a stricly medical activity — while formally laying down the conditions of such research. In the second case involving situations, on the contrary, this field becomes more narrowed while the obligations of those implementing it widen. This is, in fact, the case of committees entrusted with the mission of protecting people, whose opinions are required prior to any research, and the power of health authorities both regarding prevention and supervision, or possible sanctions. The challenge is indeed a sizable one for law, since having « sacrificed » the absolute character of the inviolability of the person, it must now demonstrate its efficiency on a daily basis

Bioethics, law and European integration

Bioethics is always described as implying a multidisciplinary and pluralistic approach of the issues encompassed. No doubt that the law and lawyers have deeply contributed to its origin and present development. However, conversely to the United States, it seems that bioethics has opened some new perspectives to the law in Europe. First, it forced the law to move out of its own frontiers and to apply its reasoning to life sciences issues with the consequence that some consider that the legal norms are used to legitimate unlawful practices while others believe legal norms have imposed binding conditions to the free development of science and technology. Second, Europe is the only region of the world where biomedical techniques are subjected to legal and sometimes binding harmonisation. In some way, we may conclude that the role played by the law in the elaboration of European bioethics is just an example of the important role of the law in the European integration

Dengue Virus Genome Uncoating Requires Ubiquitination

The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. IMPORTANCE: Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade regarding molecular aspects of the fusion step, but little is known about the events that follow this process, which leads to viral RNA release from the nucleocapsid. Here, we investigated the fate of nucleocapsid components (capsid protein and viral genome) during the infection process and found that capsid is degraded by the ubiquitin-proteasome system. However, in contrast to that observed for other RNA and DNA viruses, dengue virus capsid degradation was not responsible for genome uncoating. Interestingly, we found that dengue virus genome release requires a nondegradative ubiquitination step. These results provide the first insights into dengue virus uncoating and present new opportunities for antiviral intervention.Fil: Byk, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iglesias, Nestor Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: de Maio, Federico Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gebhard, Leopoldo German. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Комунікативні моделі текстів документів міжнародно-правового характеру (Communicative models of the text of international legal documents)

У статті проаналізовано характеристики комунікативного процесу. Охарактеризовано моделі комунікації у міжнародно-правових угодах. Автори акцентують увагу на комплексному підході до комунікативних моделей. Розкрито багатокомпонентний характер процесу комунікації у контексті творення текстів документів міжнародноправового характеру. (The article analyses characteristics of communicative process and models of communication in international legal agreements. The authors take an integrated approach to communicative models due to which they reveal the multicomponent nature of the communication in the context of writing international legal documents. The contents of communicative, interactive, perceptive elements of communicative process are characterized and the interplay and interdependence between these elements revealed. Basic stages of communicative activity in the formation of international legal documents reflected in the structure of the texts are analyzed: the preamble of a document contains motivations and intentions while target and executive (practical) components are revealed in the main body of international legal agreements. The results of the research presented in the article show the necessity of broader research basis through focusing on the communicative elements in international relations.

Bioetički aspekti robotike u kirurgiji

Julian Huxley, founder and the first Director-General of UNESCO, is at the heart of contemporary debates on the nature and objectives of the concept of transhumanism, which he first used in the early 1950s. Therefore, the analysis of his idea of transhumanism - a tool to improve the quality of life and the condition of man - should lead us to question his heritage in terms of philosophy that inspires UNESCO’s action as it seeks to build a comprehensive approach to artificial intelligence that takes into account, among other things, the values and principles of universal ethics and aims to derive the best from the use of this technology.This title where the British biologist, the elder brother of the famous science fiction writer, Aldous Huxley, author of the Brave New World1, coexists with the United Nations Organization in charge of Education of Science and Culture is obvious for those who know the history of this international organization or who like radio games: Julian Huxley was appointed as the first Director-General of UNESCO in 1946. But, beyond this evidence, there is a deeper link that highlights the history of the renewal of the idea of transhumanism (I) and questions about the role that UNESCO has, among the other international organizations (II)Julian Huxley, osnivač i prvi generalni direktor UNESCO-a, u središtu je suvremenih rasprava o prirodi i ciljevima koncepta transhumanizma, koji je prvi put upotrijebio početkom pedesetih godina prošlog stoljeća. Analiza njegove ideje o transhumanizmu - alatu za poboljšanje kvalitete života i stanja čovjeka - trebala bi nas, stoga, dovesti do toga da njegovu baštinu propitkujemo u smislu filozofije koja nadahnjuje UNESCO-vo djelovanje jer želi izgraditi cjelovit pristup umjetnoj inteligenciji koji uzima u obzir, između ostalog, vrijednosti i principe univerzalne etike i teži upotrijebiti najbolje od te tehnologije. Naslov ovog rada, u kojem britanski biolog, stariji brat slavnog pisca znanstvene fantastike Aldousa Huxleyja, autora romana “Hrabri novi svijet”, koegzistira s organizacijom Ujedinjenih naroda za obrazovanje znanost i kulturu, razumljiv je za one koji znaju povijest ove međunarodne organizacije ili one koji vole radijske igre: Julian Huxley imenovan je prvim generalnim direktorom UNESCO-a 1946. godine. No, osim ovih činjenica postoji i dublja poveznica koja ističe povijest obnove ideje transhumanizma (I) i propituje ulogu UNESCO-a među ostalim međunarodnim organizacijama (II)

Economic evaluation of cochlear implantation

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

Ueber einige Derivate des Pyrimidins

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Exploradores del espacio interio r: jóvenes contraculturales en la revista Eco Contemporáneo (1961-1969)

El objetivo de este trabajo es ubicar a la revista cultural Eco Contemporáneo, publicada entre 1961 y 1969 con un rol protagónico de Miguel Grinberg, en el escenario de la juventud contracultural de la época. El público al que apuntó la revista fueron los llamados mufados: jóvenes críticos de la sociedad y alejados de la militancia política, que proclamaban una revolución interior para la construcción de una nueva conciencia. A partir del análisis tanto de los elementos formales como del contenido, se analizará a la revista como un vehículo de comunicación con el exterior, donde el cosmopolitismo fue siempre la norma. Se investigará también el lugar y las características que tuvo en la publicación el americanismo dentro del cual los Estados Unidos desempeñaron un rol conflictivo, y cómo el objetivo de la revista viró en 1964: pasó de la construcción de una unión continental a la de una comunidad de jóvenes mufados. Eco Contemporáneo se ubicó así como un órgano de expresión de la juventud contracultural

Regularity, Variability and Bi-Stability in the Activity of Cerebellar Purkinje Cells

Recent studies have demonstrated that the membrane potential of Purkinje cells is bi-stable and that this phenomenon underlies bi-modal simple spike firing. Membrane potential alternates between a depolarized state, that is associated with spontaneous simple spike firing (up state), and a quiescent hyperpolarized state (down state). A controversy has emerged regarding the relevance of bi-stability to the awake animal, yet recordings made from behaving cat Purkinje cells have demonstrated that at least 50% of the cells exhibit bi-modal firing. The robustness of the phenomenon in vitro or in anaesthetized systems on the one hand, and the controversy regarding its expression in behaving animals on the other hand suggest that state transitions are under neuronal control. Indeed, we have recently demonstrated that synaptic inputs can induce transitions between the states and suggested that the role of granule cell input is to control the states of Purkinje cells rather than increase or decrease firing rate gradually. We have also shown that the state of a Purkinje cell does not only affect its firing but also the waveform of climbing fiber-driven complex spikes and the associated calcium influx. These findings call for a reconsideration of the role of Purkinje cells in cerebellar function. In this manuscript we review the recent findings on Purkinje cell bi-stability and add some analyses of its effect on the regularity and variability of Purkinje cell activity