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    Galassi, Vanesa

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    Interacciones de proteínas periféricas FABPs con membranas lipídicas : el rol de la electrostática

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    Tesis (Doctor en Ciencia Químicas) – Universidad Nacional de Córdoba, 2013.Fil: Galassi, Vanesa V. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.La asociación reversible de proteínas solubles a membranas lipídicas es fundamental para una amplia variedad de funciones celulares, presentando implicancias en la modulación conformado. En el presente trabajo de tesis se abordó el estudio del proceso de asociación de dos proteínas periféricas de la familia de las FABPs (proteínas que unen ácidos grasos) a membranas lipídicas, desde un enfoque estructural y termodinámico. Estas proteínas son transportadores de ligandos hidrofóbicos, por lo que su actividad fisiológica se encuentra íntimamente vinculada a la asociación a membranas. El intercambio de ligando ocurre a través de un cambio conformacional que está modulado por la interfase. Se han propuesto dos mecanismos alternativos para la transferencia de la molécula cargo: colisional y difusionaL Estos mecanismos presentan requerimientos configuracionales, ya que la orientación que la proteína adopta en la interfase resulta crucial para discernir entre uno u otro. Se estudió el proceso de modulación conformacional de estas proteínas en la interfase lipídica a través de técnicas espectroscópicas corno la fluorescencia y la absorción infrarroja (FT-IR). Se analizaron cualitativamente los resultados en términos de equilibrios conformacionales en que se pueblan diversos estados que constituyen mínimos locales en el embudo de potencial de plegamiento de la proteína en solución. Se focalizó en la selectividad de estas proteínas por interfases aniónicas, elucidando el rol mayoritario de la interacción electrostática en el proceso de asociación. Este análisis fue abordado a partir del establecimiento de correlaciones entre la afinidad por membranas o características espectroscópicas que reflejaran el grado de desplegamiento de las proteínas, y propiedades eléctricas de las membranas. Junto con trabajos previos del grupo, se puso en evidencia que la orientación de estas proteínas en la interfase está determinada mayoritariamente por la interacción del macrodipolo con el campo eléctrico de la membrana. La orientación fue obtenida a partir de simulaciones de dinámica molecular, y validada experimentalmente por medio de ensayos de filtración y de transferencia de energía resonante de fluorescencia (FRET) entre residuos Trp de la proteína y aceptores anclados en la región superficial de la membrana. El carácter dipolar de la interacción fue reflejado a través de estudios de asociación y orientación de las proteínas en membranas catiónicas. Se encontró que se asocian selectivamente a VII Interacciones de proteínas peri(éricas FABPs con membranas lipídicas: el rol de la electrostática membranas cargadas, ya sea aniónicas o catiónicas, independientemente de la carga neta de la proteína. Su orientación interfasial responde a la interacción del macrodipolo con el campo eléctrico de la membrana.Fil: Galassi, Vanesa V. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Simulations of the optical activity of voltage sensitive probes in polarized model membranes

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    Voltage sensitive dyes (VSD) are widely used to determine membrane potential both in imaging diagnosis field and in scientific research. However, their application is limited by their sensibility and rate of response [1]. We are developing a thorough computational study of optically active molecules sensitive to membrane potential. As sample cases, we chose di-3-ANEPPDHQ, widely used for in vitro determinations [2]; and indocyanine green (ICG), an infrared fluorescent dye with FDA approval for medical use [3]. The mechanism of response of these chromophores is basically electrochromic, i.e. the stationary electronic states responsible for the optical activity (light absorbance and fluorescence emission) are sensitive to the external electric field. Thus, the challenge in this kind of study is to combine the electronic description of the dye, prohibitive over a couple of hundreds atoms, with the complex condensed phase of biological systems, which is in turn determinant of the external field magnitude and fluctuations. We built atomistic models for the probes embedded in polarized membrane bilayers, and performed enhanced sampling calculations to determine the potential of mean force for membrane insertion, in order to establish the energetics of the partition process and to deconvolute the configurational contribution to the optical response. We appealed to the time-dependent resolution of Kohn-Sham equations (TD-DFT) and hybrid potentials from quantum mechanics and molecular mechanics (QM/MM) to calculate the absorption spectra of the VSDs. We obtained the spectral shifts corresponding to different configurations of the dye in the bilayer: adsorbed and inserted, and differential response to the transmembrane potential. The long-term objective is to develop a methodology that allows the study and molecular optimization of CSVs.Fil: Galassi, Vanesa Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Sosa, Micaela. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: del Popolo, Mario Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaXLVIII Reunión Anual de la Sociedad Argentina de BiofísicaSan LuisArgentinaUniversidad Nacional de San LuisSociedad Argentina de Biofísic

    Variations on the Author

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    “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

    Enhanced Adsorption Response of pH-Sensitive Peptides: The Role of Membrane Acidity

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    pH-sensitive peptides bind and traverse lipid membranes in response to changes in pH. They can be used to target tumors and other acidic tissues. We investigate the influence of acidic lipids on the pH-driven adsorption of recently synthesized peptides. Using a statistical-thermodynamic theory that takes into account the acid?base chemistry of peptides and lipids, we find that the presence of acidic lipids amplifies changes in peptide surface concentration when transitioning from high to low pH. We study cyclic and linear peptides, containing tryptophan, glutamic acid, and arginine residues, examining their behavior in both neutral and acidic membranes. Membrane binding consistently results from the shallow insertion of tryptophan residues with hydrophilic residues facing the aqueous solution. Regardless of the pH, the peptide?s geometry predominantly determines the orientation and distribution of residues. Notably, we find that not only the extent of adsorption is pH-sensitive but also the underlying adsorption mechanism: it is barrier-free at low pH but hindered by a large free energy barrier at high pH. Hence, under more acidic conditions, pH-sensitive peptides show facilitated adsorption both kinetically and thermodynamically.Fil: Chiarpotti, Maria Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Galassi, Vanesa Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Longo, Gabriel Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: del Popolo, Mario Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentin

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We 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

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    We 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

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