66 research outputs found

    MuSK is required for anchoring acetylcholinesterase at the neuromuscular junction

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    At the neuromuscular junction, acetylcholinesterase (AChE) is mainly present as asymmetric forms in which tetramers of catalytic subunits are associated to a specific collagen, collagen Q (ColQ). The accumulation of the enzyme in the synaptic basal lamina strictly relies on ColQ. This has been shown to be mediated by interaction between ColQ and perlecan, which itself binds dystroglycan. Here, using transfected mutants of ColQ in a ColQ-deficient muscle cell line or COS-7 cells, we report that ColQ clusterizes through a more complex mechanism. This process requires two heparin-binding sites contained in the collagen domain as well as the COOH terminus of ColQ. Cross-linking and immunoprecipitation experiments in Torpedo postsynaptic membranes together with transfection experiments with muscle-specific kinase (MuSK) constructs in MuSK-deficient myotubes or COS-7 cells provide the first evidence that ColQ binds MuSK. Together, our data suggest that a ternary complex containing ColQ, perlecan, and MuSK is required for AChE clustering and support the notion that MuSK dictates AChE synaptic localization at the neuromuscular junction

    Identification of pyridine analogs as new predator-derived kairomones.

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    In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a "from the wild to the lab" approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Alien Registration- Blanchard, Monique (Jay, Franklin County)

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    https://digitalmaine.com/alien_docs/20655/thumbnail.jp

    NATO Advanced Study Institute on The Frontiers of Cosmology

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    The field of Cosmology is currently undergoing a revolution driven by dramatic observational progresses and by novel theoretical scenarios imported from particle physics. This book contains lectures by world experts in the various branches of this field corresponding to lectures presented during the School "Frontiers of the Universe" at the IESC, (Corsica,France). These pedagogical lectures cover major subjects relevant to the field ( inflation; CMB: anisotropies and polarization; quintessence/dark energy; inflation; CMB: anisotropies and polarization; clusters of galaxies; gravitational lensing; galaxy formation; dark matter; supernovae and the accelerating expansion of the Universe), providing invaluable introductory material appropriate to PhD students as well as to more senior scientists who wish to become familiar with the various domains of the modern developments in Cosmolog

    In extenso n°2: Architecture domestique et mentalités. Les traités et les pratiques, XVIe - XIXe siècle

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    Étude sur les principes de distribution de l'habitation élaborés par les architectes et la façon dont ils structurent le quotidien. Un bilan des savoirs sur la distribution, l'évolution des mentalités et des modes relationnels a été dressé à partir de l'analyse des traités d'architecture, de savoir-vivre, des travaux d'historiens de l'époque et d'aujourd'hu

    La tourbière de la base de plein air de Sainte-Foy : quatre décennies de changements floristiques

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    L’objectif de cette étude était de reconstituer les changements floristiques survenus dans la tourbière de la base de plein air de Sainte-Foy (ville de Québec) entre 1978 et 2015, notamment à la suite du processus de boisement qui semble s’opérer. Les objectifs spécifiques étaient d’identifier les espèces dont la fréquence et l’abondance ont le plus changé et d’évaluer comment ces changements ont modifié la composition floristique globale de la tourbière. Trente-cinq placettes échantillonnées en 1978 ont été rééchantillonnées en 2015. La flore de la tourbière est beaucoup plus riche maintenant qu’en 1978 (hausse de 152 % de la richesse spécifique) et le cortège floristique des deux années diffère fortement (indice de dissimilarité de Sørensen de 0,62). Les espèces typiques des milieux humides sont celles qui ont le plus diminué en fréquence et en abondance, alors que celles associées à des habitats forestiers ont augmenté de façon importante. Une diversification biotique (hausse de la diversité bêta) a également été observée, ce qui indique que les assemblages floristiques sont désormais plus différents d’une placette d’échantillonnage à l’autre qu’en 1978. Des actions pouvant être prises pour assurer la protection de la tourbière sont discutées.The present study aimed to reconstruct the floristic evolution of the bog at the Base de plein air de Sainte-Foy (Québec City, Québec, Canada) between 1978 and 2015, particularly considering the tree encroachment apparently occurring at the site. The specific objectives were to identify which species had shown the greatest change in frequency and abundance, and to assess how such modifications had altered the overall floristic composition of the bog. Thirty-five plots sampled in 1978 were re-sampled in 2015. There was a 152% increase in plant richness between the two sample dates, and the plant assemblages were markedly different (Sørensen dissimilarity index of 0.62). There was a notable decrease in the frequency and abundance of typical wetland associated species over time. By contrast, forest-associated species increased significantly. Biotic differentiation (an increase in beta diversity) was also observed, indicating that plant assemblages differed more between sampling plots in 2015 than they did in 1978. Management approaches for the protection of the bog are discussed
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