Effect of DNA repair deficiencies on the cytotoxicity of resveratrol

Numerous preclinical studies have shown that the naturally-occurring polyphenol resveratrol may produce health-beneficial effects in a variety of disorders, including cancer, diabetes, Alzheimer, and cardiovascular diseases. Resveratrol has entered clinical trials for the prevention and treatment of several of these disorders. This polyphenol is also available in the market as a dietary supplement. Experimental data have shown, however, that resveratrol induces DNA damage in a variety of cells. Here we review such evidence and evaluate the cytotoxicity of resveratrol (MTT assay) in cells deficient in several major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, and Fanconi anemia repair). Cells deficient in base excision repair (EM9), nucleotide excision repair (UV4 and UV5) and Fanconi Anemia (KO40) were slightly hypersensitive to resveratrol-induced cytotoxicity with respect to their parental cells (AA8). Our results suggest that these pathways may participate in the repair of the DNA damage induced by resveratrol and that deficiencies in these pathways may confer hypersensitivity to the genotoxic activity of this dietary constituen

General research patterns in accounting: analysis of a sample of universities in Spain

En España, las sucesivas reformas universitarias han tenido, entre sus objetivos potenciar la investigación universitaria, estableciendo requisitos de acceso y promoción cada vez más claramente ligados a la actividad investigadora y definiendo de forma más precisa (y estricta) qué se considera un output de investigación aceptable. Con carácter general, la aplicación sistemática de estos criterios de evaluación ha llevado un incremento notable de la productividad científica en términos de presencia en bases de datos internacionales. Sin embargo, frente a estos efectos, positivos (mayor internacionalización, orientación a la investigación publicada en revistas de impacto), otros autores alertan de una caída de los resultados de investigación y del reconocimiento asociado en nuestra área. En esta línea, el principal objetivo de este estudio es analizar el impacto de dichas políticas en la producción científica de los profesores de contabilidad en las universidades españolas tanto públicas como privadas. Para ello se procede a determinar una muestra de universidades españolas, identificar a todos los profesores de contabilidad adscritos a dichas universidades y recopilar su producción científica en el período 2005-marzo de 2014 (en el que los criterios de evaluación ya están bastante definidos). La conclusión principal que se obtiene de este estudio es que en el periodo considerado hay un conjunto relativamente elevado de profesores con una producción científica baja, y que la producción de trabajos considerados “de impacto” se concentra en un número relativamente reducido de profesores. Esta baja producción se concentra, para las públicas, en las categorías laborales con perfil no investigador y en los TEU y también es muy alta en los profesores de universidades privadas.Recent University laws reforms in Spain sought to promote research by setting promotion and tenure criteria increasingly more related to research production and also by defining more specifically what could be considered acceptable outputs. In general terms, the systematic application of such criteria has caused an increase of research productivity in terms of presence in international databases and journals. However there are also some undesired effects, as some part of the academic staff could be reducing their research output and accounting research could be undervalued by new standards. In this line the main aim of the present research is to investigate the effect of such policies on the accounting academic production in Spain in both public and private owned universities. A sample of accounting university teachers was identified and the research opuput for those teachers included sought and analysed. The studied period covered 2005-2014, when new criteria were more internalized by academics. The main conclusion of our study is that the perceived improvement (in terms of high impact papers) is very concentrated on a small part of the population, whereas for the vast majority the effects have been the contrary: discourage for research. The vast majority of staff presents a low research production that is very acute on non-research contracts, tenured non-doctors (TEU) and private Universities teachers

Research patterns of successful accounting academics in Spain

En los últimos 25 años, la investigación contable en España ha mejorado sustancialmente en cantidad, calidad y visibilidad. Al igual que en otros países, esta mejora se atribuye a la introducción de sistemas objetivos de evaluación de la actividad académica. La literatura, sin embargo, también resalta que la aplicación de estos sistemas, basados en el uso de listados de revistas y rankings, conlleva efectos no deseados. Entre éstos se destacan: la concentración en un tipo único de output, el abandono de temas, formas y medios de divulgación no valorados, la aparición de tácticas de publicación y la preeminencia del dónde publicar sobre el qué publicar. En última instancia estos factores pueden aumentar la brecha entre investigación y profesión. Este trabajo analiza la producción científica de los profesores de contabilidad cuya trayectoria está siendo reconocida como exitosa y que, por tanto, puede considerarse como un modelo a seguir, especialmente por los académicos con menos experiencia. Respecto a otros trabajos, cubrimos un periodo más amplio y reciente, empleamos clasificaciones más detalladas e introducimos una comparación longitudinal. Esto debería permitir apreciar más claramente el cambio de pautas inducido por los sistemas de evaluación. Los resultados indican una adaptación clara a los sistemas de evaluación. Las aportaciones menos valoradas disminuyen sustancialmente en peso (revistas profesionales, participaciones en libros, incluso revistas listadas en otros índices como SJR-Scopus) y el esfuerzo se concentra en las revistas académicas más reconocidas (primeros cuartiles del JCR). Dada la escasez de revistas contables en los primeros cuartiles, las publicaciones mejor posicionadas son revistas de áreas adyacentes. También se aprecia una concentración del esfuerzo en determinadas áreas y metodologías y un ligero aumento del número de coautorías.Accounting research in Spain has substantially improved in quality, visibility and quantity, due to the implementation of research assessment processes. However, the literature warns on adverse effects of such evaluations, which rely heavily on restricted journal lists (increased focus on a unique output, discarding less valued topics, methodologies or media; careerism and gamesmanship as academics pay more attention to where-to-publish than to what-to-research; increase of the research gap, etc.). The objective of this paper is to analyse the research outputs of Spanish accounting academics that successfully passed a research accreditation, and therefore, could be taken as models to follow by entry-level academics. In addition to the focus on successful academics, this paper covers a longer and more recent period, uses more detailed classifications of outputs including different indexes and considers a longitudinal perspective; allowing a better observation of changes in publishing patterns induced by the assessment systems. Our results indicate a concentration in the most valued output (articles in listed journals, preferably in top positions) at the expense of practitioner-oriented journals, participation in books and even journals listed in less valued databases. Given the scarcity of accounting journals in relevant positions, highest impact papers are published in related areas journals

Time resolution analysis of detectors based on plastic scintillators coupled to silicon photomultipliers

The performance of several trigger counters based on plastic scintillators with silicon photomultiplier readout is investigated with cosmic rays. Efficiency and time resolution are measured using digital waveform analysis. The obtained results are relevant for trigger subsystems of Multi-Purpose Detector (MPD) and Baryonic Matter at the Nuclotron (BM@N) at the NICA heavy-ion collider. The results show very high efficiency and good timing performance of the counters

VICARED: A Neural Network Based System for the Detection of Electrical Disturbances in Real Time

The study of the quality of electric power lines is usually known as Power Quality. Power quality problems are increasingly due to a proliferation of equipment that is sensitive and polluting at the same time. The detection and classification of the different disturbances which cause power quality problems is a difficult task which requires a high level of engineering knowledge. Thus, neural networks are usually a good choice for the detection and classification of these disturbances. This paper describes a powerful system for detection of electrical disturbances by means of neural networks

Syndromes leading to failure: an exploratory research.

Prediction of corporate failure research typically focused on the design of multivariate prediction models for the discrimination betw een failed and non-failed firms. This research atracted some criticism due to the inability to formulate generally applicable models. Several reasons may have led to the im possibility of formulating such models: it has been argued that firms suffering financial distress may have incentives to manipulate accounting information in order to increase users’ confidence; statisti cal techniques could overadjust prediction models; and finally, the existence of different failure processes is not considered by prior research. The main objective of the present research is to investigate the unique characteristics of failed companies, the reasons for each particular failure and the presence of different failure processes. The present study aims to be the first step in the opening of a new stage in the development of a theoretical framework on corporate failure. It is assumed that there exist different paths to failure, instead of a simple differentiation between healthy and failed firms. This is the main contribution of the paper, which is relevant to both researchers and practitioners. It opens up new possibilities for future research, following new experimental designs. For practitioners, it constitutes a new framework for the development of decisi on-aid tools (raising the opportunity to use decision making systems based on different rules or models for different paths)

Procesos de fracaso empresarial en PYMES. Identificación y contrastación empírica.

La investigación sobre fracaso empresarial tiene como objetivo el diseño de modelos predictivos. Hasta ahora, la investigación existente utiliza un mismo planteamiento: la separación de las empresas en dos categorías, sanas y fracasadas. Aunque estos modelos llegan a proporcionar tasas iniciales de éxito aceptables, su uso posterior muestra una cierta inestabilidad predictiva y escasa fiabilidad en contextos diferentes a los iniciales. Este trabajo investiga la existencia de diferentes procesos de fracaso , primer paso para el desarrollo de un nuevo marco teórico para futuros diseños experimentales, que superen el modelo simplista de dicotomía sanas / fracasadas

El concepto de la derivada en el contexto de la enseñanza de la física, recursos para el uso de diferenciales y las tecnologías de información y comunicación

El concepto de la derivada es imperativo en el ámbito de la física. Sin embargo, con frecuencia en su enseñanza, este concepto y otros aparecen apresuradamente, fuera de cualquier contexto didáctico. El enfoque histórico que se ha dado a los conceptos relacionados puede contribuir a la comprensión de los estudiantes. Además, las Tecnologías de Información y Comunicación (TIC) utilizadas para modelar fenómenos permiten la organización de redes y la promoción de laboratorios virtuales. De esta manera los estudiantes tendrán una gran variedad de enfoques tanto para comprender los fenómenos físicos como el lenguaje en el que se explican. En nuestro caso, se pretende discutir algunas cuestiones en las que surge la necesidad de utilizar la derivada para describir diferentes comportamientos físicos. También es nuestra intención proponer estrategias didácticas menos tradicionales que aprovechen el uso de las tecnologías digitales como videograbación, Video-análisis por smartphones, sensores, entre otras cosas para enseñar tanto los aspectos físicos y matemáticos de los temas estudiados

A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells

Recent evidence suggests that cardiac glycosides might be used for the treatment of cancer. The ornamental shrub Nerium oleander has been used in traditional medicine for treating several disorders including cancer, and extracts from the leaves of this plant have already entered phase I clinical trials. In this communication, we have prepared a hydroalcoholic extract from the leaves of Nerium oleander (containing 4.75 ± 0.32 % of cardenolides) and have assessed its cytotoxic activity in A549 lung cancer cells vs. MRC5 nonmalignant lung fibroblasts. The results showed that the cytotoxicity of the Nerium oleander extract against the cancer cell line was significantly higher than that against the nonmalignant cell line, with a potency and selectivity similar to those of the anticancer drug cisplatin. Pretreatment of A549 cells with the antioxidants N-acetylcysteine and catalase slightly prevented the cytotoxicity of the extract, therefore suggesting that the formation of reactive oxygen species participates in its cytotoxic activity but does not play a major role. Nerium oleander extract-induced cytotoxicity and DNA damage (gamma-H2AX focus formation) were slightly higher in cells lacking BRCA2 (deficient in homologous recombination repair) than in parental cells; this indicates that the induction of DNA damage may also play a role in the cytotoxicity of the extract. Nerium oleander extract induced a marked inhibition of glycolysis (glucose consumption and lactate production) in A549 cells, comparable to that of the glycolysis inhibitor dichloroacetate (currently in clinical development for cancer therapy). Because platinum compounds are widely used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with the extract and found a moderate synergism when Nerium oleander extract was administered after cisplatin but a moderate antagonism when it was added before cisplatin. Our results suggest that extracts from Nerium oleander might induce anticancer effects in patients with lung cancer and support their possible advancement into phase II clinical trials for the treatment of this type of cancer

Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee