Search

Open access within the scientific community depends on the scientific context and the practices of the field. In the biomedical domain, the communication of research is characterised by the importance of the peer reviewing process, the existence of a hierarchy among journals and the transfer of copyright to the editor. Biomedical publishing has become a lucrative market and the growth of electronic journals has not helped lower the costs. Indeed, it is difficult for today's public institutions to gain access to all the scientific literature. Open access is thus imperative, as demonstrated through the positions taken by a growing number of research funding bodies, the development of open access journals and efforts made in promoting open archives. This article describes the setting up of an Inserm portal for publication in the context of the French national protocol for open-access self-archiving and in an international context.

International audience; The impact factor of scientific reviews, calculated by the Institute for Scientific Information (ISI), is increasingly used to evaluate the performance of scientists and programmes. Bibliometric indicators, originally designed for other purposes than individual evaluation, are very useful tools provided their interpretation is not extrapolated beyond their limits of validity. Here we present a critical analysis of appropriate uses and misuses of bibliometric data based on case studies. We also outline anticipated consequences of new information technologies, such as electronic journals or open access schemes, on the mode of science production, evaluation and dissemination in biomedical sciences.

International audience; Open access within the scientific community depends on the scientific context and the practices of the field. In the biomedical domain, the communication of research results is characterised by the importance of the peer reviewing process, the existence of a hierarchy among journals and the transfer of copyright to the editor. Biomedical publishing has become a lucrative market and the growth of electronic journals has not helped lower the costs. Indeed, it is difficult for today's public institutions to gain access to all the scientific literature. Open access is thus imperative, as demonstrated through the positions taken by a growing number of research funding bodies, the development of open access journals and efforts made in promoting open archives. This article describes the setting up of an Inserm portal for publication in the context of the French national protocol for open-access self-archiving and in an international context.

Ce panorama a été construit à partir des échanges et réflexions conduites au sein du groupe des responsables IST des EPST et des EPIC. Ce groupe existe depuis quatre ans et a été animé pendant plusieurs années par Geneviève Lacombe, de l'INRA. Il l'est aujourd'hui par Marie-Françoise Chevallier-Le-Guyader de l'INRA et moi-même. Il regroupe douze établissements publics de recherche, qui ont pour tutelle commune le Ministère de la Recherche. Nous nous réunissons trois à quatre fois par an pour échanger sur des sujets d'actualité et des problématiques administratives, techniques, économiques et managériales communes. Nous disposons d'invités permanents: une représentante de la tutelle, Claude Legris du Ministère de la Recherche, et un représentant du consortium Couperin, François Cavalier de l'Université de Lyon, ou Pierre Chourreu de l'Université de Toulouse, ou Louis Klee de Nice. Dans le cadre de nos exercices respectifs, la fonction IST s'inscrit: - comme une mission statutaire pour les établissements de recherche; - c'est une composante du processus de recherche; - c'est une fonction entièrement dédiée au service de la communauté scientifique; - cela peut constituer un axe de rapprochement et de mutualisation entre les établissements de recherche; - c'est un outil permettant d'accroître la visibilité des établissements que ce soit dans le cadre de la valorisation et de la diffusion des résultats et savoirs issus de nos communautés scientifiques, ou dans la constitution d'indicateurs.

International audience; The impact factor of scientific reviews, calculated by the Institute for Scientific Information (ISI), is increasingly used to evaluate the performance of scientists and programmes. Bibliometric indicators, originally designed for other purposes than individual evaluation, are very useful tools provided their interpretation is not extrapolated beyond their limits of validity. Here we present a critical analysis of appropriate uses and misuses of bibliometric data based on case studies. We also outline anticipated consequences of new information technologies, such as electronic journals or open access schemes, on the mode of science production, evaluation and dissemination in biomedical sciences.

Le présent ouvrage est « l’édition » des différents textes qui ont été rédigés et discutés lors del’Expertise Collective. Quelques modifications dans le découpage des chapitres ont étéintroduites, afin de rendre l’ensemble plus homogène et sa lecture plus logique, tout en évitantcertaines redondances.La coordination éditoriale a été assurée par Marcel Goldberg, Denis Hémon et DominiqueDouguet.Le corps principal de l’ouvrage est consacré à l’analyse des connaissances les plus récentesdisponibles concernant les principaux éléments permettant de comprendre les risques pour lasanté humaine des différentes circonstances d’exposition à l’amiante :- rappel du contexte historique, de l’évolution des méthodes de mesure, et des donnéesgénérales concernant les risques de cancer du poumon et de mésothéliome de la plèvre.- caractéristiques physico-chimiques de l’amiante, méthodes de métrologie et d’évaluationdes expositions individuelles.- synthèse des principales circonstances d’exposition et des niveaux qui y sont attachés.- risques de cancer du poumon et de mésothéliome : pour les raisons présentées plus haut,cette partie a été plus largement développée ; elle inclut une revue des mécanismes de lacancérogenèse associée à l’amiante, et une importante section consacrée aux donnéesépidémiologiques. L’accent a notamment été mis sur les éléments permettant de juger desrisques à niveaux « faibles » d’exposition, et sur la quantification des risques de cancer dupoumon et de mésothéliome, ainsi que sur l’estimation des risques théoriques associé àdifférentes conditions d’exposition (niveau, durée, âge).- effets non cancéreux des exposition à l’amiante.- risques pour d’autres localisations cancéreuses (larynx et localisations extra-thoraciques).On trouvera à la fin de l’ouvrage la reproduction du rapport de synthèse, tel qu’il a été remisaux ministères ayant commandité l’Expertise Collective, et rendu public en Juillet 1996.Outre un résumé des principaux résultats présentés dans cet ouvrage, le rapport de synthèsecomporte une section de recommandations élaborée collectivement.La rédaction du présent ouvrage intervient plus de 10 ans après que le premier grouped’expertise mis en place par les autorités gouvernementales des Etats-Unis se soit penché surl’évaluation des risques pour la santé liés aux expositions à l’amiante et après que cinq autresgroupes d’expertise aux Etats-Unis, en Grande Bretagne et au Canada se soient prononcés surcette même question. Chacun de ces groupes comportait plusieurs spécialistes des risques liésaux expositions à l’amiante et a travaillé pendant de nombreux mois pour procéder à unelecture approfondie et, dans un certain nombre de cas, à une réanalyse statistique complètedes travaux publiés. Ces travaux de synthèse ne pouvaient raisonnablement être ignorés et ilsont évidemment joué un rôle important dans la rédaction du présent texte.

International audience; Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.

Life history theory accounts for variations in many traits involved in the reproduction and survival of living organisms, by determining the constraints leading to trade-offs among these different traits. The main life history traits of phages—viruses that infect bacteria—are the multiplication rate in the host, the survivorship of virions in the external environment, and their mode of transmission. By comparing life history traits of 16 phages infecting the bacteria Escherichia coli, we show that their mortality rate is constant with time and negatively correlated to their multiplication rate in the bacterial host. Even though these viruses do not age, this result is in line with the trade-off between survival and reproduction previously observed in numerous aging organisms. Furthermore, a multiple regression shows that the combined effects of two physical parameters, namely, the capsid thickness and the density of the packaged genome, account for 82% of the variation in the mortality rate. The correlations between life history traits and physical characteristics of virions may provide a mechanistic explanation of this trade-off. The fact that this trade-off is present in this very simple biological situation suggests that it might be a fundamental property of evolving entities produced under constraints. Moreover, such a positive correlation between mortality and multiplication reveals an underexplored trade-off in host–parasite interactions., A comparison of life-history traits of 16 phages infecting E. coli reveals that although these viruses don't age, there is a trade-off between mortality and growth rate, which parallels that observed in many other species.

International audience; Amorphic mutations in the NF- kappa B essential modulator (NEMO) cause X-dominant incontinentia pigmenti, which is lethal in males in utero, whereas hypomorphic mutations cause X-recessive anhidrotic ectodermal dysplasia with immunodeficiency, a complex developmental disorder and life-threatening primary immunodeficiency. We characterized the NEMO mutation 110_111insC, which creates the most-upstream premature translation termination codon (at codon position 49) of any known NEMO mutation. Surprisingly, this mutation is associated with a pure immunodeficiency. We solve this paradox by showing that a Kozakian methionine codon located immediately downstream from the insertion allows the reinitiation of translation. The residual production of an NH(2)-truncated NEMO protein was sufficient for normal fetal development and for the subsequent normal development of skin appendages but was insufficient for the development of protective immune responses.

Previously, we reported that the hetero-tetrameric adaptor complex AP-2 co-localizes with the static population of clathrin spots, whereas it is excluded from clathrin spots that disappear from the plasma membrane (forming clathrin-coated vesicles). More recently however, another group provided evidence that AP-2 markers could be observed coincident with disappearing clathrin spots. Thus, we tested several possible explanations for the apparent discrepancies in these two studies. We evaluated the potential contribution of nonred emission of clathrin-dsRed (used in both studies) in the simultaneous measurement of AP-2 and clathrin at various times. Additionally, we directly compared two different green fluorescent protein-tagged AP-2 constructs (similar to those used in the previous reports). These studies demonstrated that the duration of expression time greatly influences the subcellular localization of the AP-2 markers. Furthermore, we quantitatively evaluated the AP-2 fluorescence at the sites of numerous static and disappearing clathrin spots (at least 80 per group) and confirmed our initial observation that while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots. Finally, in order to verify that clathrin spot disappearance represents clathrin-coated vesicle internalization, we simultaneously imaged clathrin and the cargo molecule transferrin at the cell surface.

Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden “ignition” of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of “inattentional blindness,” in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness., Computer simulations of the circuits of activity in the cerebral cortex and underlying thalamus suggest that precisely controlled oscillatory states can control the central neural processing of sensory information

Background— Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium. Methods and Results— When infected with adenovirus containing β-galactosidase (β-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, α 3 β 1 was downregulated in aging cardiac myocytes. Blocking the β 1 component of α 3 β 1 further decreased infectivity, suggesting that the interaction between the penton base of the adenovirus and β 1 maybe a crucial component of the viral entry mechanism. Conclusions— These results suggest that it is integrin-stimulated internalization rather than the adenovirus-CAR interaction that plays a vital role in adenoviral entry. The downregulation of integrins observed in senescent cells may be a key mechanism accounting for the decrease in viral infectivity seen in these cells. These findings have implications for the gene therapy treatment of myocardial failure in the elderly.

Imitation is a natural mechanism involving perception-action coupling which plays a central role in the development of understanding that other people, like the self, are mental agents. PET was used to examine the hemodynamic changes occurring in a reciprocal imitation paradigm. Eighteen subjects (a) imitated the actions of the experimenter, (b) had their actions imitated by the experimenter, (c) freely produced actions, or (d) freely produced actions while watching different actions made by the experimenter. In a baseline condition, subjects simply watched the experimenter's actions. Specific increases were detected in the left STS and in the inferior parietal cortex in conditions involving imitation. The left inferior parietal is specifically involved in producing imitation, whereas the right homologous region is more activated when one's own actions are imitated by another person. This pattern of results suggests that these regions play a specific role in distinguishing internally produced actions from those generated by others.

Parsing a mental operation into components, characterizing the parallel or serial nature of this flow, and understanding what each process ultimately contributes to response time are fundamental questions in cognitive neuroscience. Here we show how a simple theoretical model leads to an extended set of predictions concerning the distribution of response time and its alteration by simultaneous performance of another task. The model provides a synthesis of psychological refractory period and random-walk models of response time. It merely assumes that a task consists of three consecutive stages-perception, decision based on noisy integration of evidence, and response-and that the perceptual and motor stages can operate simultaneously with stages of another task, while the central decision process constitutes a bottleneck. We designed a number-comparison task that provided a thorough test of the model by allowing independent variations in number notation, numerical distance, response complexity, and temporal asynchrony relative to an interfering probe task of tone discrimination. The results revealed a parsing of the comparison task in which each variable affects only one stage. Numerical distance affects the integration process, which is the only step that cannot proceed in parallel and has a major contribution to response time variability. The other stages, mapping the numeral to an internal quantity and executing the motor response, can be carried out in parallel with another task. Changing the duration of these processes has no significant effect on the variance.

0022 One of the key characteristics of retroviruses is their ability to integrate a copy of the DNA reverse-transcribed from their viral RNA genome into host cell DNA. This integration is mediated by a preintegration complex (PIC) comprising viral DNA, reverse transcriptase, and integrase, as well as poorly characterized host proteins [1]. It is this property that makes retroviruses good vectors for the transfer of therapeutic genes, and many such vectors have been made.

Alternative polyadenylation sites produce transcript isoforms with 3′ untranslated regions (UTRs) of different lengths. If a microRNA (miRNA) target is present in the UTR, then only those target-containing isoforms should be sensitive to control by a cognate miRNA. We carried out a systematic examination of 3′ UTRs containing multiple poly(A) sites and putative miRNA targets. Based on expressed sequence tag (EST) counts and EST library information, we observed that levels of isoforms containing targets for miR-1 or miR-124, two miRNAs causing downregulation of transcript levels, were reduced in tissues expressing the corresponding miRNA. This analysis was repeated for all conserved 7-mers in 3′ UTRs, resulting in a selection of 312 motifs. We show that this set is significantly enriched in known miRNA targets and mRNA-destabilizing elements, which validates our initial hypothesis. We scanned the human genome for possible cognate miRNAs and identified phylogenetically conserved precursors matching our motifs. This analysis can help identify target-miRNA couples that went undetected in previous screens, but it may also reveal targets for other types of regulatory factors., Synopsis MicroRNAs (miRNAs) are short RNA molecules that recognize specific target sequences in the 3′ region of mRNAs. These miRNAs can then specifically keep the mRNAs from being expressed, or translated into proteins. In this article, the authors ask what happens when a targeted mRNA has several forms differing by their 3′ regions. Such 3′ variations are very common. If two or more variations are present in a single mRNA, the result is two or more mRNAs with 3′ ends of different lengths. If an miRNA target is located between the two sites of variability, the shorter transcript should be target free and should escape miRNA-mediated inhibition, while longer transcripts should be inhibited. To test this hypothesis, the authors looked at mRNAs that had these variable 3′ ends. Variants containing targets for certain miRNAs appeared to be specifically underrepresented in tissues where these particular miRNAs are found. This principle was used to find other sequence patterns in 3′ regions that had a similar effect, and a list of 312 significant patterns was obtained. The authors then scanned genome sequences and identified possible cognate miRNAs for these patterns. This new knowledge will help further an understanding of how genes are controlled.