323,092 research outputs found
Dissecting the Extracellular Complexity of Neuromuscular Junction Organizers
No full textSynapse formation is a very elaborate process dependent upon accurate coordination of pre and post-synaptic specialization, requiring multiple steps and a variety of receptors and signaling molecules. Due to its relative structural simplicity and the ease in manipulation and observation, the neuromuscular synapse or neuromuscular junction (NMJ)—the connection between motor neurons and skeletal muscle—represents the archetype junction system for studying synapse formation and conservation. This junction is essential for survival, as it controls our ability to move and breath. NMJ formation requires coordinated interactions between motor neurons and muscle fibers, which ultimately result in the formation of a highly specialized post-synaptic architecture and a highly differentiated nerve terminal. Furthermore, to ensure a fast and reliable synaptic transmission following neurotransmitter release, ligand-gated channels (acetylcholine receptors, AChRs) are clustered on the post-synaptic muscle cell at high concentrations in sites opposite the presynaptic active zone, supporting a direct role for nerves in the organization of the post-synaptic membrane architecture. This organized clustering process, essential for NMJ formation and for life, relies on key signaling molecules and receptors and is regulated by soluble extracellular molecules localized within the synaptic cleft. Notably, several mutations as well as auto-antibodies against components of these signaling complexes have been related to neuromuscular disorders. The recent years have witnessed strong progress in the understanding of molecular identities, architectures, and functions of NMJ macromolecules. Among these, prominent roles have been proposed for neural variants of the proteoglycan agrin, its receptor at NMJs composed of the lipoprotein receptor-related protein 4 (LRP4) and the muscle-specific kinase (MuSK), as well as the regulatory soluble synapse-specific protease Neurotrypsin. In this review we summarize the current state of the art regarding molecular structures and (agrin-dependent) canonical, as well as (agrin-independent) non-canonical, MuSK signaling mechanisms that underscore the formation of neuromuscular junctions, with the aim of providing a broad perspective to further stimulate molecular, cellular and tissue biology investigations on this fundamental intercellular contact
Phasing protein structures using the group–subgroup relation
No full textDiffraction data from two non-isomorphous crystals (forms 1 and 2) of an artificial protein with a four-helix bundle motif, di-CoII-DF1-L13A, have been collected using synchrotron radiation. The phase of form 1 has been assigned using the group and minimal non-isomorphic supergroup relation between the space group of the previously determined di-MnII-DF1-L13G structure and the space group of this form. This unconventional method of solving the phase problem has also been tested with form 2 using a reverse relation. The structure of the latter form has been solved using the group and maximal non-isomorphic subgroup relation with the space group of form 2 of the analogous dimanganese protein. This application has shown that this phasing method can be used for solving the protein structures of polymorphic crystals as an alternative to the molecular-replacement method
Effect of different extraction and precipitation methods on yield and quality of pectin
No full textAn experimental study has been conducted to determine the combined effects of different extraction conditions and precipitation method on the yield and quality of high methoxyl pectin from lemon peels. Pectin was extracted using different mineral acids (HCl, HNO3 and H2SO4) at four concentration levels (0.025; 0.05; 0.1 and 0.2 m), at 70 °C for 4 h. The soluble pectin was precipitated by iso-propanol or by an aluminium sulphate, Al 2(SO 4) 3, solution at pH 4. The extraction with HCl and HNO 3, at the highest concentrations investigated, followed by aluminium precipitation led to the best results in terms of yield (22-25%), quality and gelling power of pectin with a remarkable decrease of alcohol consumption as compared to the alcoholic precipitation under the same extracting conditions
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The application of Lake Shorezone Functionality Index (SFI): a valid tool to assess the reproductive sites status of bleak (Alburnus arborella)
No full text
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Electroencéphalographie et interfaces cerveau-machine : nouvelles méthodes pour étudier les états mentaux
No full textAvec les avancées technologiques dans le domaine de l'imagerie cérébrale fonctionnelle et les progrès théoriques dans la connaissance des différents éléments neurophysiologiques liés à la cognition, les deux dernières décennies ont vu l'apparition d'interfaces cerveau-machine (ICM) permettant à une personne d'observer en temps réel, ou avec un décalage qui se limite à quelques secondes, sa propre activité cérébrale. Le domaine clinique en général, et plus particulièrement celui de la neuropsychologie et des pathologies conduisant à un handicap moteur lourd, pour lesquels les applications potentielles sont nombreuses qu'elles soient thérapeutiques ou en vue d'une réhabilitation fonctionnelle, a constitué un moteur important de la recherche sur ce nouveau domaine des neurosciences temps réel. Parmi ces applications, le neurofeedback, ou neurothérapie, qui vise l'acquisition par le sujet du contrôle volontaire de certains aspects de son activité cérébrale en vue de les amplifier ou au contraire les diminuer dans un but thérapeutique, voire d'optimisation cognitive, représente une technique prometteuse, alternative aux thérapies et traitements médicamenteux. Cependant, la validation de ce type d'intervention et la compréhension des mécanismes mis en jeux en sont encore à leurs balbutiements. L'entraînement par neurofeedback est souvent long, pouvant s'étaler sur plusieurs semaines. Il est donc très probable que ce type de rééducation cérébrale sollicite des phénomènes de plasticité qui s'inscrivent dans une dynamique lente, et de ce fait, requiert une durée relativement longue d'entraînement pour atteindre les effets à long terme recherchés. Cependant, à cela peuvent s'ajouter de nombreux éléments perturbateurs qui pourraient être à l'origine de la difficulté de l'apprentissage et des longs entraînements nécessaires pour obtenir les résultats attendus. Parmi eux, les perturbations qui viennent déformer le signal enregistré, ou les éléments artefactuels qui ne font pas partie du signal d'intérêt, sont une première cause potentielle. Le manque de spécificité fonctionnelle du signal retourné au sujet pourrait en constituer une deuxième. Nous avons d'une part développé des outils méthodologiques de traitement du signal en vue d'améliorer la robustesse des analyses des signaux EEG, principalement utilisés jusqu'à maintenant dans le domaine du neurofeedback et des ICM, face aux artefacts et au bruit électromagnétique. D'autre part, si l'on s'intéresse au problème de la spécificité fonctionnelle du signal présenté au sujet, des études utilisant l'IRM fonctionnelle ou des techniques de reconstruction de sources à partir du signal EEG, qui fournissent des signaux ayant une meilleure spécificité spatiale, laissent entrevoir de possibles améliorations de la vitesse d'apprentissage. Afin d'augmenter la spécificité spatiale et la contingence fonctionnelle du feedback présenté au sujet, nous avons étudié la stabilité de la décomposition de l'EEG en différentes sources d'activité électrique cérébrale par Analyse en Composantes Indépendantes à travers différentes séances d'enregistrement effectuées sur un même sujet. Nous montrons que ces décompositions sont stables et pourraient permettre d'augmenter la spécificité fonctionnelle de l'entraînement au contrôle de l'activité cérébrale pour l'utilisation d'une ICM. Nous avons également travaillé à l'implémentation d'un outil logiciel permettant l'optimisation des protocoles expérimentaux basés sur le neurofeedback afin d'utiliser ces composantes indépendantes pour rejeter les artefacts en temps réel ou extraire l'activité cérébrale à entraîner. Ces outils sont utiles dans le cadre de l'analyse et de la caractérisation des signaux EEG enregistrés, ainsi que dans l'exploitation de leurs résultats dans le cadre d'un entraînement de neurofeedback. La deuxième partie de ce travail s'intéresse à la mise en place de protocoles de neurofeedback et à l'impact de l'apprentissage. Nous décrivons tout d'abord des résultats obtenus sur une étude pilote qui cherche à évaluer chez des sujets sains l'impact d'un protocole de neurofeedback basé sur le contrôle du rythme Mu. Les changements comportementaux ont été étudiés à l'aide d'un paradigme de signal stop qui permet d'indexer les capacités attentionnelles et d'inhibition de réponse motrice sur lesquelles on s'attend à ce que l'entraînement ICM ait une influence. Pour clore cette partie, nous présentons un nouvel outil interactif immersif pour l'entraînement cérébral, l'enseignement, l'art et le divertissement pouvant servir à évaluer l'impact de l'immersion sur l'apprentissage au cours d'un protocole de neurofeedback. Enfin, les perspectives de l'apport des méthodes et résultats présentés sont discutées dans le contexte du développement des ICMs de nouvelle génération qui prennent en compte la complexité de l'activité cérébrale. Nous présentons les dernières avancées dans l'étude de certains aspects des corrélats neuronaux liés à deux états mentaux ou classes d'états mentaux que l'on pourrait qualifier d'antagonistes par rapport au contrôle de l'attention : la méditation et la dérive attentionnelle, en vue de leur intégration à plus long terme dans un entraînement ICM par neurofeedback.With new technological advances in functional brain imaging and theoretical progress in the knowledge of the different neurophysiologic processes linked to cognition, the last two decades have seen the emergence of Brain-Machine Interfaces (BCIs) allowing a person to observe in real-time, or with a few seconds delay, his own cerebral activity. Clinical domain in general, and more particularly neuropsychology and pathologies leading to heavy motor handicaps, for which potential applications are numerous, whether therapeutic or for functional rehabilitation, has been a major driver of research on this new field of real-time neurosciences. Among these applications, neurofeedback, or neurotherapy, which aims the subject to voluntary control some aspects of his own cerebral activity in order to amplify or reduce them in a therapeutic goal, or for cognitive optimization, represents a promising technique, and an alternative to drug treatments. However, validation of this type of intervention and understanding of involved mechanisms are still in their infancy. Neurofeedback training is often long, up to several weeks. It is therefore very likely that this type of rehabilitation is seeking brain plasticity phenomena that are part of slow dynamics, and thus require a relatively long drive to achieve the desired long-term effects. However, other disturbing elements that could add up to the cause of the difficulty of learning and long training sessions required to achieve the expected results. Among them, the disturbances that come from recorded signal distortions, or artifactual elements that are not part of the signal of interest, are a first potential cause. The lack of functional specificity of the signal returned to the subject could be a second one. We have developed signal processing methodological tools to improve the robustness to artifacts and electromagnetic noise of EEG signals analysis, the main brain imaging technique used so far in the field of neurofeedback and BCIs. On the other hand, if one looks at the issue of functional specificity of the signal presented to the subject, studies using functional MRI or source reconstruction methods from the EEG signal, which both provide signals having a better spatial specificity, suggest improvements to the speed of learning. Seeing Independent Component Analysis as a potential tool to increase the spatial specificity and functional contingency of the feedback signal presented to the subject, we studied the stability of Independent Component Analysis decomposition of the EEG across different recording sessions conducted on the same subjects. We show that these decompositions are stable and could help to increase the functional specificity of BCI training. We also worked on the implementation of a software tool that allows the optimization of experimental protocols based on neurofeedback to use these independent components to reject artifacts or to extract brain activity in real-time. These tools are useful in the analysis and characterization of EEG signals recorded, and in the exploitation of their results as part of a neurofeedback training. The second part focuses on the development of neurofeedback protocols and the impact of learning. We first describe the results of a pilot study which seeks to evaluate the impact of a neurofeedback protocol based on the Mu rhythm control on healthy subjects. The behavioral changes were studied using a stop signal paradigm that indexes the attentional abilities and inhibition of motor responses on which the BCI training can possibly have influence. To conclude this section, we present a new tool for immersive interactive brain training, education, art and entertainment that can be used to assess the impact of immersion on learning during a neurofeedback protocol. Finally, prospects for methods and results presented are discussed in the context of next-generation BCI development which could take brain activity complexity into account. We present the latest advances in the study of certain aspects of the neural correlates associated with two mental states or classes of mental states that could be described as antagonistic with respect to the control of attention: meditation and mind wandering, for their integration in the longer term in an BCI training using neurofeedback
Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases
No full textOxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone. Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study. Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment
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