Síntesis de péptidos multifuncionales que contienen un fluoróforo como sonda fluorescente

Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2016, Tutor: Ernesto Nicolás GalindoAlzheimer Disease (AD) is the most common cause of dementia in the elderly population. Symptoms of the disease are: difficulty in remembering newly learned information, mood and behaviour changes, memory loss, judgment alteration and difficulties in daily and usual activities. Today Alzheimer disease affects more than 30 million people worldwide and it is estimated that more than 100 million people will be affected by 2050 mainly because of the fast growth of the elderly population. Currently, it is generally accepted that Alzheimer disease originates from a process called amyloid cascade that occurs in the synaptic cleft, wherein A aggregation due to its union with Cu(II), is a key event. In this work, elaborated in collaboration with the group of Bioinorganic Chemistry led by Professor Patrick Gámez, the peptides with sequences Ac-His-Lys(Cm)-His-Lys-NH2 and Ac-His-Lys(4-DMN)-His-NH2 have been synthesized. These peptides encompass two amino acid derivatives containing two fluorescent probes: coumarin and 4-N,N-dimethylamino-1,8-naphthalimido. These peptide sequences will be studied as potential therapeutic agents due to its chelating properties of the Cu (II), as well as copper sensors for AD diagnosis.The amino acid derivatives have been synthesized in aqueous phase while peptides were synthesized in solid phase through the Fmoc strategy, using as polymer support Rink Amide resin. The peptides prepared were functionalized with an acetyl group in the N-terminus and a carboxamide group in the C-terminus. To obtain the desired synthetic sequence, Fmoc amino acids, protected at the N-terminus with the 9-fluorenylmethoxycarbonyl group (Fmoc), which is labile to piperidine, were used. For generating the amide bonds, N,N'-diisopropycarbodiimide (DIC) and Oxyma have been used. The cleavage of the peptide from the resin was performed under acidic conditions using trifluoroacetic acid (TFA) in the presence of triisopropylsilane (TIPS) as carbocation scavenger agent. The characterization of the products was carried out using different techniques such as 1H and 13C NMR, HPLC and HPLC-MS

SIGPAC y series multitemporales LANSAT 15 TM como estrategia híbrida de clasificación de usos de suelo para aplicaciones hidrológicas

El objetivo de este trabajo consiste en la obtención de un mapa de usos y coberturas de suelo para su integración en un modelo hidrológico de balance de agua a lo largo de 2009. Los resultados de dicha aplicación (evapotranspiración, humedad de suelo, necesidades de riego) se obtienen a escala de parcela, con escala temporal diaria y contemplando los usos y coberturas más frecuentes en la zona. La herramienta diseñada para aplicar el modelo (HidroMORE, Modelo Hidrológico de Estimación de Recarga y Evapotranspiración) proporciona los resultados en forma de mapa imagen. Con este fin, se presenta una alternativa híbrida de clasificación consistente en la combinación de la base de datos vectorial del Sistema de Información Geográfica de Parcelas Agrícolas (SIGPAC), junto con una serie multitemporal de imágenes Landsat 5 TM (Thematic Mapper) del año 2009. El primero aporta la definición parcelaria, mientras que la segunda provee la información suficiente para resolver clases poco definidas en el SIGPAC, especialmente la categoría ‘tierra arable’. Se utilizaron metodologías de teledetección como la clasificación, la segmentación multitemporal y el NDVI (Normalized Difference Vegetation Index), junto con herramientas SIG. El método propuesto supuso una mejora global de la precisión respecto a un método de clasificación supervisada convencional del 20% para la zona de estudio en 2009, y con un coste operacional muy bajo.The aim of this work consists on retrieving a land use-land cover map in order to integrate it in a water balance model along 2009. The results of this application, i.e., evapotranspiration, soil moisture, irrigation rates, are obtained at field scale, in a daily basis, and over the most representative agricultural uses. The model is implemented in a computerized tool, HidroMORE, which provides image maps of the results. A hybrid alternative of classification is presented for such hydrological application. It consisted in a combination of the vectorial database from the Spanish Geographic Information System for Agricultural Plots (SIGPAC) and a Landsat 5 TM multitemporal series of images for the year of study. The SIGPAC affords the spatial shape of the plots, whereas the images allow the segmentation of some ambiguous categories, i.e., ‘agricultural plots’. Remote sensing techniques (classification, segmentation, and NDVI, Normalized Difference Vegetation Index) were used, as well as GIS tools. The proposed method improved by 20% the global accuracy comparing to a typical supervised classification in the study area along 2009, while the computational cost is low

Correlation between Leg Length Discrepancy, Load Distribution and Structural Alterations in Lower Limb

[Resumen] Objetivo: Establecer la relación entre la diferencia de longitud, el reparto de carga en bipedestación y las alteraciones estructurales del miembro inferior. Material y métodos: Se realizó un estudio descriptivo, observacional, transversal con una muestra de 31 pacientes (49.1% hombres/58.1% mujeres). Se obtuvieron variables antropométricas y sociodemográficas, medición de las extremidades inferiores, ángulo Q y del valgo del calcáneo y evaluación del reparto de carga en el miembro inferior. Resultados: Se obtuvo una concordancia casi perfecta (k = 0,9; p = 0,000) entre las mediciones espina ilíaca antero superior- maléolo externo y espina ilíaca antero superior- maléolo interno. Conclusiones: Tras determinar la irrelevancia de tomar unas referencias óseas u otras, se ha obtenido que el miembro inferior izquierdo es más largo en la mayoría de la población siendo mayor el reparto de carga en el retropié de la pierna más corta.[Abstract] Objective: to establish the relationship between the difference in length, the distribution of the load in the standing position and the structural alterations of the lower limb. Material and Methods: A descriptive, observational, cross-sectional study was carried out with a sample of 31 patients (49.1% men / 58.1% women). Anthropometric and sociodemographic variables were obtained, measurement of the lower extremities, Q angle and calcaneal valgus and evaluation of the load distribution in the lower limb. Results: An almost perfect concordance (k = 0.9; p = 0.000) was obtained between the measurements of the anterior superior iliac spine-external malleolus and the anterior superior iliac spine-internal malleolus. Conclusions. After determining the irrelevance of taking some bone landmarks or others, it has been obtained that the lower left limb is longer in the majority of the population, with greater load distribution on the hindfoot of the shorter leg

Glycosyl conjugation to G-quadruplex ligands as a strategy to improve their antitumor and antiparasitic efficacy.

Congresos y Conferencias: Comunicación de Congreso - Conferencia invitada

Fernando Huarte Morton (1921-2011): libro homenaje

La figura de Fernando Huarte Morton (1921-2011) tiene un gran significado para el mundo de las bibliotecas, el libro antiguo y la bibliografía española y goza de un profundo respeto, simpatía y admiración para todos aquellos que le conocieron y trataron personalmente. Desarrolló la mayor parte de su carrera profesional en la Biblioteca de la Universidad Complutense de Madrid, de la que fue director entre 1975 y 1986, contribuyendo a su modernización desde varios ámbitos: el reconocimiento institucional; la profesionalización del personal; la centralización de los fondos; la normalización de los procesos y servicios; el inicio de la mecanización del catálogo y la preocupación por el fondo antiguo y por la existencia de un edificio para albergar la gran biblioteca general. Con estas acciones, las bases de la biblioteca del siglo XXI estaban puestas. Es por este motivo, que la Biblioteca de la Universidad Complutense, institución a la que dedicó tantos años de su vida, quiera rendirle un sentido homenaje a través de la publicación de este libro en el que participan muchos de los bibliotecarios que le conocieron y que han querido dar a conocer su profesionalidad como bibliotecario, su rigor científico como estudioso e investigador y su atrayente personalidad llena de sentido del humor y de ironía

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study

Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.11 página

Pauta de observación de la enseñanza de las matemáticas en Educación Secundaria en España (POEMat.ES)

POEMat.ES es una pauta de observación de las prácticas de enseñanza de profesores de matemáticas de Educación Secundaria grabadas en vídeo. Este instrumento permite recoger información sobre las acciones de los profesores de matemáticas en el aula desde 3 dimensiones diferentes, organizadas a su vez en 17 subdimensiones. Cada subdimensión se puede valorar en cuatro niveles de desempeño que describen características concretas de las acciones realizadas por el profesor observadas en un fragmento de vídeo. POEMat.ES ha sido desarrollada con el objetivo inicial de ofrecer una visión equilibrada y multidimensional de la enseñanza de las matemáticas en Educación Secundaria en el contexto español

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of &gt;1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with &gt;1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p &lt;0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p &lt;0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p &lt;0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p &lt;0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p &lt;0.001) and more oHE development (35% vs. 49%, p &lt;0.001) than those with S-TSA. Conclusion: This study suggests that TSA &gt;83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.Jonel Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57, CRC1382), Cellex Foundation and European Union’s Horizon 2020 research and innovation program GALAXY study (No. 668031), LIVERHOPE (No. 731875) and MICROB-PREDICT (No. 825694) and the Cellex Foundation. Joan Genescà is a recipient of a Research Intensification grant from Instituto de Salud Carlos III, Spain. The study was partially funded by grants PI15/00066, and PI18/00947 from Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivasis supported by Instituto de Salud Carlos III. Macarena Simón-Talero is a recipient of the grant JR 17/00029 from Instituto de Salud Carlos II