DNA-binding determinants promoting NHEJ by human Polm

Non-homologous end-joining (NHEJ), the preferred pathway to repair double-strand breaks (DSBs) in higher eukaryotes, relies on a collection of molecular tools to process the broken ends, including specific DNA polymerases. Among them, Polο is unique as it can catalyze DNA synthesis upon connection of two non-complementary ends. Here, we demonstrate that this capacity is intrinsic to Polο, not conferred by other NHEJ factors. To understand the molecular determinants of its specific function in NHEJ, the interaction of human Polο with DNA has been directly visualized by electromobility shift assay and footprinting assays. Stable interaction with a DNA gap requires the presence of a recessive 5′-P, thus orienting the catalytic domain for primer and nucleotide binding. Accordingly, recognition of the 5′-P is crucial to align the two DNA substrates of the NHEJ reaction. Site-directed mutagenesis demonstrates the relevance of three specific residues (Lys 249, Arg253 and Arg416) in stabilizing the primer strand during end synapsis, allowing a range of microhomology-induced distortions beneficial for NHEJ. Moreover, our results suggest that the Polο BRCT domain, thought to be exclusively involved in interaction with NHEJ core factors, has a direct role in binding the DNA region neighbor to the 5′-P, thus boosting Polο-mediated NHEJ reactions. © 2012 The Author(s).Ministerio de Ciencia y Tecnología; Fundación Ramón Areces;Comunidad Autónoma de MadridPeer Reviewe

Construcción y calibración de un equipo isopiéstico para la determinación de coeficientes osmóticos y coeficientes de actividad

Se describe un equipo isopiéstico para la determinación de los coeficientes osmóticos de soluciones acuosas, usando cloruro de sodio como sustancia de referencia a temperaturas de 288,15 K, 293,15 K y 298,15 K. Los tiempos de equilibrio estuvieron entre 12 y 20 días para concentraciones de 0,1 a 0,6 m. Los coeficientes osmóticos de las soluciones acuosas de KCl obtenidos a partir del método isopiéstico y los coeficientes de actividad calculados fueron comparados con datos de literatura

“Global” graph problems tend to be intractable

AbstractA notion of “information-flow complexity” is used to formally measure the degree to which a graph problem is a “global” problem (in the sense of “global” vs. “local” optimization). Under this measure a number of intractable problems including VERTEX COVER, GRAPH 3-COLORABILITY, HAMILTONIAN CIRCUIT, and other NP-complete problems are exponentially more “global” than a number of tractable problems including EDGE COVER, GRAPH 2-COLORABILITY, EULERIAN CIRCUIT, and other problems in P

Contribución a la familia Braconidae (Hymenoptera: Ichneumonoidea) del estado de Aguascalientes

Braconidae es la segunda familia de Hymenoptera con mayor diversidad en el mundo, e incluye parasitoides de insectos y de otros artrópodos. Para Aguascalientes, hasta 2017, sólo se conocían siete subfamilias, ocho géneros y cuatro especies. En el presente trabajo se recolectaron 608 adultos de Braconidae correspondientes a 18 subfamilias, 44 géneros, tres especies y 107 morfoespecies, obtenidos en 111 localidades de los once municipios; de las cuales, 11 subfamilias, 39 géneros y tres especies corresponden a nuevos registros para la entidad. Este trabajo permitió incrementar el registro a 18 subfamilias, 47 géneros y siete especies de Braconidae para el estado de Aguascalientes. La mayoría de los géneros son cosmopolitas y las especies son Neárticas y Neotropicales. Los géneros más abundantes fueron Opius, Aphidius, Trioxys y Aleiodes.Braconidae is the second most diverse Hymenoptera family in the world, which includes parasitoids of insects and other arthropods. Until 2017, only seven subfamilies, eight genera and four species were known in Aguascalientes. In this research, 608 adults of Braconidae family, corresponding to 18 subfamilies, 44 genera, three species and 107 morphospecies, were obtained in 111 localities of eleven municipalities; from those, 11 subfamilies, 39 genera and three species are new records for the state. This work allowed increasing the registry to 18 subfamilies, 47 genera and seven species of Braconidae for the State of Aguascalientes. Most genera are cosmopolitan, and the species are Nearctic and Neotropical. The most abundant genera were Opius, Aphidius, Trioxys and Aleiodes

A new pharmacogenetic algorithm to predict the most appropriate dosage of acenocoumarol for stable anticoagulation in a mixed Spanish population

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (<11 mg/week, 11-21 mg/week, >21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases.This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Ciencia y profesión : el farmacéutico en la historia

474 páginas. Versiones pdf / epubLas IV Jornadas Científicas de la Sociedad de Docentes Universitarios de Historia de la Farmacia (SDUHFE) se celebraron en la Sede de La Rábida en junio de 2016. Esta obra presenta diversas investigaciones y comunicaciones, con varias temáticas que pueden desglosarse en cuatro bloques: 1) En un primer grupo podemos considerar todos los capítulos que abordan la historia de los colegios farmacéuticos así como los avatares de la profesión. Se da cuenta en la provincia de Sevilla de las dificultades del Colegio de Farmacéuticos en el periodo de la Guerra Civil y la Posguerra (1936-1949), del proceso de colegiación obligatoria a partir de 1916, pinceladas históricas sobre los farmacéuticos cántabros del siglo XIX, del Colegio de Farmacéuticos de Filipinas a finales del XIX, de los conflictos de los farmacéuticos en las reuniones sanitarias de mitad del XX, y del papel de los farmacéuticos titulares en la potabilización de las aguas de consumo en Plentzia (Vizcaya). 2) Podemos destacar también todos los trabajos que giran en torno a diferentes medicamentos y productos farmacéuticos, entre ellos estudios históricos sobre piedras preciosas, medicamentos para tratar heridas, quina contra las tercianas, opio, alexifármacos, medicamentos homeopáticos, talidomida o curiosos productos como el Licor del Polo. 3) El papel de los laboratorios farmacéuticos como la Casa Nestlé durante la Guerra Civil española y el franquismo, diferentes laboratorios onubenses durante este mismo periodo, el papel del Instituto de Higiene Militar y la experimentación con insecticidas clorados sintéticos en la posguerra española, aglutinan el tercer cuerpo temático. 4) Finalmente, podemos destacar los trabajos que tienen una componente publicitaria, divulgadora y social entre los que cabe destacar el estudio del NO-DO y los diferentes noticieros y documentales sobre temas farmacéuticos que resultan muy ilustrativos. La propaganda farmacéutica desarrollada en la revista Matronas, el inventario del patrimonio farmacéutico catalán, junto a la percepción social de la farmacia a través de las fallas valencianas conforma este último grupo