Síntesis y evaluación citotoxica de derivados halogenados y peracetylados de nucleósidos en celulas de cancer de mama

Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The products were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halogenated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines. Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.Objetivos: Sintetizar derivados halogenados sobre la base nitrogenada, sus respectivos derivados tipo éster o amida de todos los grupos hidroxilo y amina presentes en los nucleósidos uridina y citarabina, y evaluar su actividad citotóxica sobre una línea celular de cáncer de mama. Metodología: primero se realizó la reacción de halogenación en la posición 5 de la base nitrogenada, posteriormente se formaron los ésteres y amidas de todos los grupos hidroxilos y amino presentes en los nucleósidos. Además, se preparó el derivado acetónido con catálisis ácida. Los compuestos se caracterizaron por espectroscopía de resonancia magnética nuclear (RMN 1H y RMN 13C) y espectrometría de masas por inyección directa en modo positivo. Los derivados se evaluaron sobre líneas celulares de tumor de Ovario de Hámster Chino (CHO) y de cáncer de mamá (MCF-7). Resultados: Se obtuvieron 4 derivados mono-halogenados con cloro y bromo de la uridina y citarabina, respectivamente, sus respectivos derivados per-acetilados, los nucleósidos per-acetilados y el acetónido de la uridina; los compuestos se obtuvieron con rendimientos superiores a 90%. Los nucleósidos per-acetilados, y los derivados per-acetilados y halogenados no exhibieron una inhibición significativa de la viabilidad celular en ambas líneas celulares, sin embargo, de estos, los derivados per-acetilados y halogenados presentaron mayor actividad citotóxica que los respectivos nucleósidos per-acetilados. El derivado acetónido de la uridina mostró citotoxicidad significativa sobre ambas líneas celulares. Conclusiones: se obtuvieron los nucleósidos per-acetilados y los respectivos derivados clorados y bromados de estos, con rendimientos altos, sin embargo, estos compuestos no exhibieron una actividad anti-proliferativa significativa (p˂0,05), posiblemente debido a una baja activación intra-celular de los nucleósidos

Holocene atmospheric dust deposition in NW Spain

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.Atmospheric dust plays an important role in terrestrial and marine ecosystems, particularly those that are nutrient limited. Despite that most dust originates from arid and semi-arid regions, recent research has shown that past dust events may have been involved in boosting productivity in nutrient-poor peatlands. We investigated dust deposition in a mid-latitude, raised bog, which is surrounded by a complex geology (paragneiss/schist, granite, quartzite and granodiorite). As proxies for dust fluxes, we used accumulation rates of trace (Ti, Zr, Rb, Sr and Y) as well as major (K and Ca) lithogenic elements. The oldest, largest dust deposition event occurred between ~8.6 and ~7.4 ka BP, peaking at ~8.1 ka BP (most probably the 8.2 ka BP event). The event had a large impact on the evolution of the mire, which subsequently transitioned from a fen into a raised bog in ~1500 years. From ~6.7 to ~4.0 ka BP, fluxes were very low, coeval with mid-Holocene forest stability and maximum extent. In the late Holocene, after ~4.0 ka BP, dust events became more prevalent with relatively major deposition at ~3.2–2.5, ~1.4 ka BP and ~0.35–0.05 ka BP, and minor peaks at ~4.0–3.7, ~1.7, ~1.10–0.95 ka BP and ~0.74–0.58 ka BP. Strontium fluxes display a similar pattern between ~11 and ~6.7 ka BP but then became decoupled from the other elements from the mid Holocene onwards. This seems to be a specific signal of the granodiorite batholith, which has an Sr anomaly. The reconstructed variations in dust fluxes bear a strong climatic imprint, probably related to storminess controlled by North Atlantic Oscillation conditions. Complex interactions also arise because of increased pressure from human activities.Natural Environment Research Council (NERC)Consiliencia networkFunding for Consolidation and Structuration of Research Unit

Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

BACKGROUND: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. METHODS: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. RESULTS: From 2010 to 2012–2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012–2013 were, respectively, under 1 % and 20 L3/person/transmission season. Serology in children aged 1–10 years demonstrated that although 26 out of 396 (7 %) individuals still had Ov-16 antibodies, only 4/218 (2 %) seropositives were aged 1–5 years. CONCLUSIONS: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75 % of the Yanomami population and 70 % of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1313-z) contains supplementary material, which is available to authorized users

From social context and resilience to performance through job satisfaction: A multilevel study over time

Giving the crucial role of organizational context in shaping individual attitudes and behaviors at work, in this research we studied the effects of collective work-unit Perceptions of Social Context (PoSC) on individual work resilience and two key individual outcomes: job satisfaction and job performance as rated by the supervisor. We theorized that collective PoSC act as antecedents of individual variables, and that individual job satisfaction mediates the relationship between collective PoSC and job performance, and between work resilience and job performance over time. A sample of 305 white-collar employees, clustered in 67 work-units, participated in the study. Hierarchical linear modeling highlighted that collective PoSC are significant related to individual work resilience. Moreover, results showed that individual job satisfaction fully mediates the relationship between collective PoSC and individual job performance and the relationship between individual work resilience and individual job performance. At a practical level, results suggest that interventions on collective PoSC may increase work resilience, job satisfaction and job performance over time at the individual level

Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies

An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)’s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak

Hypomineralized Second Primary Molars as Predictor of Molar Incisor Hypomineralization

Molar incisor hypomineralization (MIH) is a developmental defect of dental enamel that shares features with hypomineralized second primary molars (HSPM). Prior to permanent tooth eruption, second primary molars could have predictive value for permanent molar and incisor hypomineralization. To assess this possible relationship, a cross-sectional study was conducted in a sample of 414 children aged 8 and 9 years from the INMA cohort in Valencia (Spain). A calibrated examiner (linear-weighted Kappa 0.83) performed the intraoral examinations at the University of Valencia between November 2013 and 2014, applying the diagnostic criteria for MIH and HSPM adopted by the European Academy of Paediatric Dentistry. 100 children (24.2%) presented MIH and 60 (14.5%) presented HSPM. Cooccurrence of the two defects was observed in 11.1% of the children examined. The positive predictive value was 76.7% (63.9-86.6) and the negative predictive value 84.7% (80.6-88.3). The positive likelihood ratio (S/1-E) was 10.3 (5.9-17.9) and the negative likelihood ratio (1-S/E) 0.57 (0.47-0.68). The odds ratio was 18.2 (9.39-35.48). It was concluded that while the presence of HSPM can be considered a predictor of MIH, indicating the need for monitoring and control, the absence of this defect in primary dentition does not rule out the appearance of MIH

Microencapsulation techniques: a proposal for microencapsulated probiotics.

A la hora de utilizar probióticos, el principal problema que se presenta, es la escasa resistencia de estos a diferentes condiciones ambientales y tecnológicas. Las técnicas de microencapsulación son un buen método para proteger a estos microorganismos, sin embargo no todas las técnicas son apropiadas para los probióticos. En este artículo proponemos la técnica de gelificación interna, que por sus características permite la obtención de un tamaño de partícula adecuado y la supervivencia de los microorganismos.The main problem when probiotics are used is the low resistance of these to different environmental and technological conditions. The microencapsulation techniques are a good method in order to protect the probiotics, Nevertheless not all techniques of microencapsulation are suitable for probiotics. In this paper, we propose the internal gelification which allows us to obtain a suitable particle size and the survival of the microorganisms

SUSTENTABILIDAD COMO OPCIÓN DE VIDA: AGRICULTURA URBANA.

Como lo propone Rondón & Gil (2015) puesto que una óptima calidad de vida no solo depende de la decodificación del ambiente en la vida cotidiana, sino que, al contrario, la falencia que se presenta en la sociedad actual refiere a la apropiación del territorio debido a la dificultad de una “educación ambiental” en el contexto colombiano.De lo anterior se implementan estrategias de concientización y cambio, desde el espacio del Club de Ciencias Infundiendo Pensamiento Científico de la I.E.D. Liceo Femenino Mercedes Nariño de manera lúdico-recreativa a través de la implementación y desarrollo de agricultura urbana, cuyo impacto a nivel socio-escolar tiene como fin mejorar la calidad ambiental minimizando las afectaciones consecuentes generando un impacto en la comunidad, sobre las dinámicas y los hechos que se vivencian a diario que perjudican a todo el planeta y nuestro entorno de forma directa o indirecta, además el cómo estas acciones perjudican a todo el planeta. A modo de colofón se observa que el taller permitió la reflexión con relación a la agricultura urbana que propende por aprovechar imaginativamente cualquier espacio disponibl

Análisis de los datos obtenidos de la red social Twitter para la identificación precoz de la tendencia al suicidio de los usuarios

Although not everyone is aware of it, data available on the Internet are very useful and have a great potential to help our society. The digital platform Twitter is a social network where people sometimes express their feelings and emotions. And this paper arises from the idea of doing an analysis of these data through a Machine Learning tool, to find a psychiatric picture of depression, and if it is possible, the associated suicidal tendency. Twitter data extraction tool has been Tweepy, and with the profile data users, it has been made, an excel database that collects the information. Next, with the Machine Learning tool called UMAP, an unsupervised analysis of the database has been carried out, thanks to which it has been possible to differentiate three groups, with a very low inter cluster distance, which suggest that each observation looks a lot like its neighbors. From these three groups, we find one which behavior or use of the platform would be associated with a normal or standard way. The two other two group of meet part of the characteristics associated with depression.  Aunque no todo el mundo sea consciente todos los datos disponibles en la red son útiles y tienen un gran potencial de ayuda a nuestra sociedad. La plataforma digital Twitter es una red social donde en ocasiones las personas expresan sus sentimientos y emociones, y este proyecto surge de la idea de hacer un análisis de estos datos de que se pueda realizar a través de una herramienta de Machine Learning un perfil típico un cuadro psiquiátrico de depresión, y si es posible la tendencia al suicidio asociada. La herramienta para la extracción de datos de Twitter utilizada ha sido Tweepy, y con los usuarios obtenidos con ésta y las características definidas para ellos, se ha generado una base de datos en formato excel en la nube One Drive que recoge toda esta información. A continuación, con la herramienta de Machine Learning llamada UMAP, se ha realizado un análisis de forma no supervisada de la base de datos, gracias al cuál se han podido diferenciar tres grupos, con una distancia intercluster muy baja, lo que quiere decir que cada observación se parece mucho a sus vecinos. De estos tres grupos hay uno al que se asociaría una conducta o uso de esta plataforma de una forma normal o estándar, y otros dos de diferente dimensión que cumplen parte de las características asociadas al trastorno de depresión