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    Estudio del efecto protector de la melatonina en el cristalino, análisis de su acción hipotensora y modulación de su secreción usando un filtro amarillo

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    Tesis inédita de la Universidad Complutense de Madrid, Facultad de Óptica y Optometría, leída el 21-04-2022El cristalino es una lente biconvexa, avascular y transparente situada en el polo anterior del ojo por detrás del iris. Su función principal es enfocar la luz a la retina. La opacificación o pérdida de transparencia del cristalino genera cataratas, la principal causa de ceguera reversible en el mundo, siendo el estrés oxidativo un mecanismo patológico clave en su desarrollo. La melatonina es una neurohormona secretada principalmente por la glándula pineal, también es producida a nivel ocular en estructuras como el cuerpo ciliar, la retina y el cristalino. La síntesis y liberación de melatonina sigue un ritmo circadiano, siendo suprimida su liberación mediante la luz por la activación del fotopigmento melanopsina. Recientes estudios han evidenciado la presencia de este fotopigmento en el cristalino y como su activación mediante luz azul disminuye la expresión de enzimas biosintéticas de la melatonina así como su producción, sugiriendo que la modificación de la luz, por ejemplo mediante el uso de filtros, podría regular la liberación de melatonina ocular. La melatonina actúa como agente antioxidante, adquiriendo así un potencial anticataratogénico. Se desconoce si los niveles de melatonina ocular presentan alguna alteración en la patología de cataratas, repercutiendo en la progresión de la enfermedad...The lens is an avascular and transparent structure located in the anterior pole of the eyeball behind the iris. Its main function is to focus light on the retina. The opacification or loss of transparency of the lens generates cataracts, which are the main cause of reversible blindness in the world. Oxidative stress is a key pathological mechanism in cataract progress.Melatonin is a neurohormone mainly secreted by the pineal gland and also produced at eye structures such as the ciliary body, the retina and the lens. The synthesis and release of melatonin follows a circadian rhythm. Melatonin release is suppressed by the activation of the photopigment melanopsin by light. Recent studies have shown the presence of melanopsin in the lens and how its activation by blue light exposure decreases the expression of enzymes involved in melatonin biosynthesis as well as neurohormone production, suggesting that light modulation, for example with filters, could regulate melatonin in the eye. Among the functions of melatonin in the eye highlights its possible role as an antioxidant agent. Taking into account the relationship of cataracts with oxidative stress, the anticataratogenic potential of melatonin has been suggested. It is unknown whether ocular melatonin levels are altered in cataracts, which could affect the disease progression...Fac. de Óptica y OptometríaTRUEunpu

    Mecanismos de regulación de la síntesis de la melatonina para el control de la presión intraocular

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    Tesis de la Universidad Complutense de Madrid, Facultad de Óptica y Optometría, Departamento de Bioquímica y Biología Molecular IV, leída el 10/11/2017Ocular hypertension, although not considered a disease itself, it leads to glaucoma which eventually cause irreversible vision loss. Consequently, glaucoma therapeutic approach is to lower intraocular pressure (IOP). Nonetheless, anti-glaucoma drugs come often with several side effects that can lead to treatment withdrawal in some cases. In this context, melatonin and its analogs emerges as potential complimentary/alternative treatment, offering the advantage of hypotensive and antioxidant properties. The present PhD thesis aim to investigate endogenous melatonin content in the aqueous humor and describes mechanisms involved in detecting increased IOP, along with a focus on the possibility of melatonin receptors to interact with different receptors with the intention to find a more effective combined therapeutical approach. Finally, to study the attribution of the crystalline lens to the aqueous humor melatonin content and to discover the regulation of its synthesis in this ocular structure. Results showed a correlation between melatonin levels in the aqueous humor and IOP. Melatonin levels were found higher in patients with elevated IOP. Using a glaucomatous animal model (DBA/2J) it was possible to corroborate our findings. In vitro assays pointed to the participation of the TRPV4 channel, which is sensitive to pressure, among other stimuli. Activation of the mentioned channel in human immortalised nonpigmented ciliary body epithelial cells resulted in an increment of melatonin secretion through the increase of aralkylamine N-acetyltransferase (AANAT) expression, the first enzyme in melatonin synthesis. In addition, short term assays showed that the TRPV4 activation leaded to AANAT phosphorylation through a cascade of intracellular events that involves the participation of calmodulin and calcium-calmodulin dependent protein kinase II. This phosphorylation activates AANAT and therefore melatonin synthesis is stimulated...La hipertensión ocular, aunque no se considera una enfermedad en sí, es un factor de riesgo para desarrollar glaucoma, que eventualmente causa pérdida irreversible de la visión. En consecuencia, el enfoque terapéutico más habitual en el glaucoma es reducir la presión intraocular (PIO). No obstante, los fármacos anti-glaucomatosos presentan varios efectos secundarios que pueden conducir a la retirada del tratamiento en algunos casos. En este contexto, la melatonina y sus análogos emergen como un tratamiento complementario/ alternativo, ofreciendo la ventaja de poseer propiedades hipotensoras y antioxidantes. La presente tesis doctoral tiene como objetivo investigar el contenido de la melatonina endógena en el humor acuoso y describir los mecanismos implicados en la detección de los cambios en la IOP. Igualmente se estudia la capacidad de los receptores de melatonina para interactuar con otros receptores con la intención de encontrar un enfoque terapéutico combinado más eficaz. Finalmente, esta tesis también estudia la contribución del cristalinoen su aporte de melatonina al humor acuoso. Los resultados han mostrado una correlación entre los niveles de melatonina en el humor acuoso y la PIO. Los niveles de melatonina se encontraron más altos en pacientes con PIO elevada. El uso de modelo animal glaucomatoso (DBA/2J) corroboró nuestros hallazgos de una manera consistente. Por otro lado, los ensayos in vitro señalaron la participación del canal TRPV4, proteína que es sensible a la presión,como principal activador de la sintesis de la melatonina. De este modo, la estimulación de este canal en células epiteliales del cuerpo ciliar no pigmentadas inmortalizadas humanas dio como resultado un incremento de la secreción de melatonina a través de un aumento de la expresion de la Aralquilamina N-acetiltransferasa(AANAT), la primera enzima en la síntesis de melatonina. Además, los ensayos a corto plazo mostraron que la activación de TRPV4 induce a la fosforilación de AANAT, y su activación, a través de una cascada de eventos intracelulares implica la participación de la calmodulina y la calmodulina quinasa II dependiente de calcio-calmodulina...Unidad Docente de Bioquímica y Biología MolecularFac. de Óptica y OptometríaTRUEunpu

    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

    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

    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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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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