1,720,959 research outputs found
Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
Get PDFAbstract: Translational motion of neurotransmitter receptors is key for determining receptor number at the synapse and hence, synaptic efficacy. We combine live-cell STORM superresolution microscopy of nicotinic acetylcholine receptor (nAChR) with single-particle tracking, mean-squared displacement (MSD), turning angle, ergodicity, and clustering analyses to characterize the lateral motion of individual molecules and their collective behaviour. nAChR diffusion is highly heterogeneous: subdiffusive, Brownian and, less frequently, superdiffusive. At the single-track level, free walks are transiently interrupted by ms-long confinement sojourns occurring in nanodomains of ~36 nm radius. Cholesterol modulates the time and the area spent in confinement. Turning angle analysis reveals anticorrelated steps with time-lag dependence, in good agreement with the permeable fence model. At the ensemble level, nanocluster assembly occurs in second-long bursts separated by periods of cluster disassembly. Thus, millisecond-long confinement sojourns and second-long reversible nanoclustering with similar cholesterol sensitivities affect all trajectories; the proportion of the two regimes determines the resulting macroscopic motional mode and breadth of heterogeneity in the ensemble population.Fil: Mosqueira, Alejo. Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurobiología Molecular; ArgentinaFil: Mosqueira, Alejo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Camino, Pablo A. Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurobiología Molecular; ArgentinaFil: Camino, Pablo A. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrantes, Francisco J. Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurobiología Molecular; ArgentinaFil: Barrantes, Francisco J. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Antibody‐induced crosslinking and cholesterol‐sensitive, anomalous diffusion of nicotinic acetylcholine receptors
No full textSynaptic strength depends on the number of cell-surface neurotransmitter receptors in dynamic equilibrium with intracellular pools. Dysregulation of this homeostatic balance occurs, for example in myasthenia gravis, an autoimmune disease characterized by a decrease in the number of postsynaptic nicotinic acetylcholine receptors (nAChRs). Monoclonal antibody mAb35 mimics this effect. Here we use STORM nanoscopy to characterize the individual and ensemble dynamics of monoclonal antibody-crosslinked receptors in the clonal cell line CHO-K1/A5, which robustly expresses adult muscle-type nAChRs. Antibody labeling of live cells results in 80% receptor immobilization. The remaining mobile fraction exhibits a heterogeneous combination of Brownian and anomalous diffusion. Single-molecule trajectories exhibit a two-state switching behavior between free Brownian walks and anticorrelated walks within confinement areas. The latter act as permeable fences (~34 nm radius, ~400 ms lifetime). Dynamic clustering, trapping, and immobilization also occur in larger nanocluster zones (120–180 nm radius) with longer lifetimes (11 ± 1 s), in a strongly cholesterol-sensitive manner. Cholesterol depletion increases the size of the clustering phenomenon; cholesterol enrichment has the opposite effect. The disclosed high proportion of monoclonal antibody-crosslinked immobile receptors, together with their anomalous, cholesterol-sensitive diffusion and clustering, provides new insights into the antibody-enhanced antigenic modulation that leads to physiopathological internalization and degradation of receptors in myasthenia. (Figure presented.).Fil: Mosqueira, Alejo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Camino, Pablo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Estudio de la dinámica y organización del receptor de acetilcolina nicotínico mediante análisis de imágenes de superresolución y técnicas avanzadas de microscopía de fluorescencia
No full textEn los últimos años, la física ha adquirido un papel preponderante en el entendimiento de la biología molecular a través de la aplicación de la mecánica estadística y el desarrollo de nuevas tecnologías (como la microscopía de superresolución o “nanoscopía”). En este trabajo, combinamos imágenes de superresolución de microscopía de reconstrucción óptica estocástica (STORM) con una serie de análisis biofísicos para estudiar la difusión lateral del receptor de acetilcolina nicotínico (nAChR) de tipo muscular adulto en la superficie de células de mamífero CHO-K1/A5. Se observó que el nAChR exhibe una dinámica altamente heterogénea. Una proporción muy importante (∼ 52 ± 22 %) se halló completamente inmóvil. La población móvil, por su parte, exhibió un comportamiento mayoritariamente subdifusivo (exponente de anomalía (β) ∼ 0.85 ± 0.23 y coeficiente de difusión generalizado Kβ ∼ 0.26 ± 0.41 μm² s^–β), junto con moléculas únicas de difusión Browniana y, otras minoritarias, superdifusivas. El ∼ 90 % de los receptores (independientemente de su modalidad difusional) exhibieron un comportamiento de difusión intermitente entre dos estados: caminatas al azar (Browniana) interrumpidas por estancias de ∼ 170-470 ms de duración en zonas de confinamiento con radios de ∼ 36 ± 13 nm y alto contenido de obstáculos. A nivel poblacional, los nAChRs forman parte de eventos de agregación supramolecular de ∼ 3.9 ± 0.8 s de duración y en zonas con radios promedio de 149 ± 13 nm. La modificación del contenido de colesterol de membrana produjo cambios tanto en la dinámica individual como en la poblacional. Por un lado, el enriquecimiento de colesterol disminuyó la proporción de trayectorias subdifusivas y aumentó considerablemente la proporción de trayectorias superdifusivas, generando un aumento en los parámetros dinámicos del receptor ((β) ∼ 0.91 ± 0.23 y (Kβ) ∼0.43 ± 0.79 μm²s^−β). Por otro lado, la reducción del colesterol se vio asociada a una desestabilización de los eventos que lo confinan y que lo agregan, reflejada en una reducción significativa de las duraciones (∼ 250-700 ms y ∼ 2.5 ± 0.1 s, respectivamente) y de los tamaños (∼ 32 ± 13 nm y ∼ 107 ± 4 nm radio, respectivamente) en donde ocurren. Por lo tanto, la combinación entre estancias de confinamiento del orden de milisegundos y eventos de auto agregación del receptor del orden de segundos, ambos dependientes de la concentración de colesterol, determina la dinámica individual y poblacional del receptor en membrana.Fil:Mosqueira, Alejo . Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
