WIPI1, BAG1 and PEX3 autophagy-related genes are relevant melanoma markers

ROS and oxidative stress may promote autophagy; on the other hand, autophagy may help reduce oxidative damages. According to the known interplay of ROS, autophagy, and melanoma onset, we hypothesized that autophagy-related genes (ARGs) may represent useful melanoma biomarkers. We therefore analyzed the gene and protein expression of 222 ARGs in human melanoma samples, from 5 independent expression databases (overall 572 patients). Gene expression was first evaluated in the GEO database. Forty-two genes showed extremely high ability to discriminate melanoma from nevi (63 samples) according to ROC (AUC ≥ 0.85) and Mann-Whitney (p < 0.0001) analyses. The 9 genes never related to melanoma before were then in silico validated in the IST online database. BAG1, CHMP2B, PEX3, and WIPI1 confirmed a strong differential gene expression, in 355 samples. A second-round validation performed on the Human Protein Atlas database showed strong differential protein expression for BAG1, PEX3, and WIPI1 in melanoma vs control samples, according to the image analysis of 80 human histological sections. WIPI1 gene expression also showed a significant prognostic value (p < 0.0001) according to 102 melanoma patients' survival data. We finally addressed in Oncomine database whether WIPI1 overexpression is melanoma-specific. Within more than 20 cancer types, the most relevant WIPI1 expression change (p = 0.00002; fold change = 3.1) was observed in melanoma. Molecular/functional relationships of the investigated molecules with melanoma and their molecular/functional network were analyzed via Chilibot software, STRING analysis, and gene ontology enrichment analysis. We conclude that WIPI1 (AUC = 0.99), BAG1 (AUC = 1), and PEX3 (AUC = 0.93) are relevant novel melanoma markers at both gene and protein levels

Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease

Modificaciones en la cabeza del sujeto de las fugas de El clave bien temperado de Johan Sebastian Bach, Libro I BWV 846 A 869, Köthen 1722, Libro II BWV 870 A 893, Leipzig 1744

Resumen: En esta colección, Bach presenta recursos aplicados a algunas de las entradas del tema en el sector central y final de las fugas, ya sea en el rol de sujeto o respuesta, consistentes en producir variaciones en la cabeza, es decir dentro de los tres sonidos iniciales. No se consignan aquí los cambios aplicados a la totalidad del tema como el movimiento contrario, la aumentación, la disminución, cambios rítmicos, y las mutaciones iniciales y finales en la respuesta tonal, y el acortamiento del sector conclusivo y variaciones en el o los últimos sonidos. Estas modificaciones tienen por objeto resaltar u ocultar la aparición del tema y son clasificadas según aspectos rítmicos, de cambio de altura y registro, de variación ornamental y distribución de sonidos en distintas voces. Finalmente se relacionan estos cambios bajo la numerología y las proporciones utilizadas por el autor.Abstract: In this collection, Bach presents resourses applied to some of the theme entries in the central and the end of the fughes, either in the role of subject or response, consisting in producing variations in the head, ie within three sounds initials. No changes are reported here applied to the whole theme as contrary motion, augmentation, reduction, rhythmic changes, and mutations in the initial and final tonal response, and shortening of the conclusive sector and changes in the last sounds. These changes are intended to highlight or hide the appearance of the theme and are classified according to rhythmic aspects, change in height and registration, ornamental variation and distribution of sounds in different voices. Finally, these changes are listed under the numerology and the proportions used by the author

Memorias del contrapunto : cuando naturaleza y arte se integran

Introducción: El origen del término contrapunto proviene de la expresión latina “punctum contra punctum” (punto contra punto, nota contra nota para nosotros) y cuyo significado es el estudio de cómo deben proceder los sonidos simultáneos (intervalos armónicos) según el sistema tonal clásico y, extendiendo el concepto, el control de dos o más líneas con características propias (voces, partes) que se ejecutan al mismo tiempo (polifonía) bajo normas preestablecidas (armonía). Según mi punto de vista, y entendiendo que las líneas musicales son una suma de intervalos melódicos, hago extensivo el estudio de cómo debe procederse, no sólo en el sentido vertical de los intervalos, sino también en el horizontal. La buena marcha de la polifonía se basa en el equilibrio entre las líneas y la simultaneidad: lo melódico y lo armónico. El fundamento del estudio de las técnicas del contrapunto clásico surge de la necesidad de profundizar y enriquecer el discurso musical polifónico poniendo en juego -y en equilibrio- la independencia y fluidez de las voces y la variedad en el desarrollo melódico y armónico, manteniendo siempre la unidad estructural presente en el Tema. Una mesurada sofisticación de las partes que, elaboradas con mayor grado de complejidad den a la obra, esencialmente del género polifónico para piano, órgano, conjuntos de cámara, coro u orquesta, mayor interés general como resultado de la suma del valor de los contenidos individuales. En un terreno filosófico, podríamos decir que la armonía es el escenario donde se desarrolla el diálogo y la convivencia de lo diverso..

Quaerendo invenietis : más allá de los números

Resumen: en este artículo se intenta demostrar que, además de la infinidad de recursos con que contaba Bach para producir un legado musical de calidad y cantidad inigualado, podía incluir contenidos extramusicales que fueran de utilidad para entender sus principios éticos y religiosos.Abstract: This article attempts to demonstrate that in addition to myriad resources available to Bach for producing a musical legacy of quality and quantity unparalleled he could include extra-musical contents that would be useful to understand his ethical and religious principles

Un peregrino proyecto de TV

Hace ya algunos años, veinte para ser preciso, nuestra querida Facultad de Artes y Ciencias Musicales cumplía 30 años al mismo tiempo que la Pontificia Universidad Católica Argentina. En esa oportunidad, motivados por la necesidad de hallar un camino para difundir la existencia de la Facultad, pensamos en elaborar un proyecto interdisciplinario que optimizara el potencial de relaciones y contactos institucionales y personales con que contabamos. Buscabamos transmitir, por medio de la imagen, una aplomada y austera solidez institucional y academica convencidos de que nuestra humilde Casa atesoraba esos principios. La otra herramienta de comunicaci6n, esta vez con el fin de alcanzar una presencia en los medios, fue la realización de un cielo televisivo de trece programas de una hora de duraci6n sobre temas musicales..

Nora Ponte's Mirrors

Esta obra, basada en textos de Ana Olagaray, propone una unidad temática, de sintaxis y de integración con el texto que excede el marco de carácter programático o complementario para convertirse en un equilibrado y sugerente resultado de imágenes musicales y literarias. Los poemas intentan motivar en el oyenteflector ideas y emociones contenidas en el relato del espejo: en Mirror (1), rojo, imágenes de caída, erotismo; en 'Broken Mirror' (11), amarillo, imágenes de temor y fragmentación; en 'Black Mirror or the Mirror of Mourning' (III), gris, imágenes de soledad y de tiempo perdido; en 'Time Begins' (IV), verde, tiempo de primavera, imágenes de crecimiento y unificación..

Determining the temperature of petroleum formation from the kinetic properties of petroleum asphaltenes

Knowledge of the timing and location of petroleum formation is important in assessing the extent of available reserves in hydrocarbon-forming basins. This can be predicted from the thermal history of a basin and the kinetic parameters that characterize the thermal breakdown of kerogen in source rocks. At present, the kinetic parameters of kerogen breakdown are experimentally determined using immature rock samples from basin margins(1), but questions remain about the accuracy of this approach(2), especially when significant variability is observed within individual source units(3-5). Here we show that the kinetics of hydrocarbon generation from petroleum asphaltenes can be used to determine the temperature conditions of the actual source rock at the time of expulsion of the sampled petroleum. This relationship reflects the structural similarity of asphaltenes to the parent kerogen(6,7). We expect that our approach may be used as a comparatively simple alternative method for assessing the petroleum generation characteristics of a given basin, which will allow for better estimates of the available oil resources and the risks associated with their exploration

Research criteria for the diagnosis of prodromal dementia with Lewy bodies.

The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation