Mesoscopic model and free energy landscape for protein-DNA binding sites: Analysis of cyanobacterial promoters

This is an open-access article distributed under the terms of the Creative Commons Attribution License.The identification of protein binding sites in promoter sequences is a key problem to understand and control regulation in biochemistry and biotechnological processes. We use a computational method to analyze promoters from a given genome. Our approach is based on a physical model at the mesoscopic level of protein-DNA interaction based on the influence of DNA local conformation on the dynamics of a general particle along the chain. Following the proposed model, the joined dynamics of the protein particle and the DNA portion of interest, only characterized by its base pair sequence, is simulated. The simulation output is analyzed by generating and analyzing the Free Energy Landscape of the system. In order to prove the capacity of prediction of our computational method we have analyzed nine promoters of Anabaena PCC 7120. We are able to identify the transcription starting site of each of the promoters as the most populated macrostate in the dynamics. The developed procedure allows also to characterize promoter macrostates in terms of thermo-statistical magnitudes (free energy and entropy), with valuable biological implications. Our results agree with independent previous experimental results. Thus, our methods appear as a powerful complementary tool for identifying protein binding sites in promoter sequences.This work was supported by the Spanish Goverment under DGICYT Projects No. FIS2011-25167, BFU2009-07424, BFU2012-31458 cofinanced by FEDER funds, Gobierno de Aragon (projects B18 and E19), “Proyecto Intramural” (BIFI) and Spanish government fellowship FPU-2012-2608 (RTR).Peer Reviewe

Physicochemical and functional properties of native and modified by crosslinking, dark-cush-cush yam (Dioscorea trifida) and cassava (Manihot esculenta) starch

Cush-cush yam (Dioscorea trifida), is a sub-utilized tropical crop, rich in starch, which grown in tropical areas. The exploitation of its starch has great potential. The objectives of this research was to modify starch isolated from dark-cush-cush yam, which grown in the Venezuelan Amazonian, and commercial cassava starch, by cross-linking, in order to characterize and compare them with their native counterparts. The results showed that differences in the amylose content affected the composition, structure and functional properties of both starches. The degree of substitution (DS) was more significant in the cush-cush starch yam than that of the cassava starch, even if both were within the ranges allowed by the FDA. The granular size of cassava starch was slightly changed by modification. The rheological properties also changed, increasing the viscosity peak, breakdown, consistency and setback. Finally, that modification method conferred great stability to the starches gelatinization.Fil: Gutiérrez, Tomy J.. Universidad Central de Venezuela; VenezuelaFil: Pérez, Elevina. Universidad Central de Venezuela; VenezuelaFil: Guzmán, Romel. Universidad Central de Venezuela; VenezuelaFil: Tapia, María Soledad. Universidad Central de Venezuela; VenezuelaFil: Fama, Lucia Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentin

Synthesis and characterization of new aromatic polyamides bearing crown ethers and acyclic ethylene oxide units in the pendant structure. III. Benzo-18-crown-6 systems and their open-chain counterparts

We report the synthesis and characterization of 10 novel polyamides containing the benzo-18-crown-6 subunit and its dipodal counterpart, along with their properties, and a comparison with homologous polyamides bearing benzo-12-crown-4, benzo-15-crown-5, and the corresponding dipodal systems. The anomalous polymerization of some of the diacid monomers, that leads to insoluble gels under standard Yamazaki polymerization conditions, is described. The gel formation has been attributed to the threading of cyclic oligoamides with a growing polyamide chain to yield rotaxanes, polyrotaxanes, catenanes, or polycatenanes. Polyamide macrocycles have been characterized with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A route to avoid gel formation, consisting of a lower initial monomer concentration, is also described, along with the polymer properties of the polyamides obtained, including the chemical characterization, mechanical behavior, water sorption, morphology, diffusion data, and permeability of membranes prepared with these polymers. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6252-6269, 200

Population pharmacokinetics of phenytoin in adult patients

Phenytoin (DPH) is an antiepileptic drug used in the first line of focal seizures and tonic-clonic seizures treatments. Phenytoin shows a highly protein binding, non-lineal dose-dependent kinetics, large pharmacokinetic variability and narrow therapeutic index; reasons why this antiepileptic is commonly monitored to optimize the efficacy/toxicity balance. The aim of the present work was to characterize the DPH pharmacokinetics in adult population./nDrug plasma levels at steady-state from 215 adult patients were used to develop a population pharmacokinetic model (PopPK) using a non-linear mixed effect modelling approach with NONMEM v.7.3./nPharmacokinetics of DPH were described following one-compartment distribution model with zero-order absorption and Michaelis-Menten non-lineal saturable elimination. Age, weight, magnitude of DPH dose and co-medication with valproic acid have been shown influence on maximum velocity of PHT elimination, significantly decreasing the variability of this pharmacokinetic parameter./nThis preliminary PopPK developed, has shown an adequate evaluation of the descriptive and predictive performance in adult population within a large dose range (50-800 mg/day). However, its implementation in the clinical setting is required to confirm its suitability.La fenitoína (DPH) es un antiepiléptico considerado de primera elección en el tratamiento de las crisis focales y convulsiones tónico-clónicas. DPH presenta elevada unión a proteínas plasmáticas, un comportamiento cinético no lineal dependiente de la dosis, elevada variabilidad cinética interindividual y un estrecho margen terapéutico; estas características aconsejan su monitorización para optimizar su balance eficacia/toxicidad. El objetivo de este trabajo fue la caracterización de la farmacocinética de DPH en población adulta./nConcentraciones en estado de equilibrio de DPH procedentes de 215 pacientes adultos fueron utilizadas para desarrollar un modelo farmacocinético poblacional (PopPK) aplicando una metodología de efectos mixtos no lineales con el programa NONMEM v.7.3./nLa cinética de DPH fue descrita adecuadamente mediante un modelo monocompartimental con absorción de orden cero y cinética de eliminación no lineal ajustada a la ecuación de Michaelis-Menten. Edad, peso, magnitud de dosis y comedicación con ácido valproico han mostrado influencia sobre la velocidad de eliminación de DPH, reduciendo su variabilidad de forma considerable./nSe ha obtenido un modelo PopPK preliminar que ha mostrado una adecuada capacidad descriptiva y predictiva en población adulta en un amplio rango de dosis (50-800 mg/día). No obstante, se precisa su aplicación en el contexto clínico para confirmar su validez

Formation of S0 galaxies through mergers Explaining angular momentum and concentration change from spirals to S0s

The CALIFA team has recently found that the stellar angular momentum and concentration of late-type spiral galaxies are incompatible with those of lenticular galaxies (S0s), concluding that fading alone cannot satisfactorily explain the evolution from spirals into S0s. Here we explore whether major mergers can provide an alternative way to transform spirals into S0s by analysing the spiral-spiral major mergers from the GalMer database that lead to realistic, relaxed S0-like galaxies. We find that the change in stellar angular momentum and concentration can explain the differences in the λ_Re-R_90/R_50 plane found by the CALIFA team. Major mergers thus offer a feasible explanation for the transformation of spirals into S0s

Optimización de las redes de tratamiento en drogodependencia mediante el uso de servicios cognitivos en la nube

La adhesión al tratamiento en el ámbito de la drogodependencia está fuertemente ligada al éxito del mismo. Sin embargo, la alta tasa de abandono en los programas relacionados con la adicción a la cocaína, es un rasgo común y creciente en la mayoría de los centros dedicados al seguimiento y recuperación de pacientes consumidores. Dado que el tratamiento de las adicciones implica un gran consumo de recursos socio-sanitarios y que los recursos especializados en drogodependencia son muy limitados, el abandono del tratamiento se convierte en un grave problema. La motivación de este trabajo es mejorar la planificación y selección de las redes terapéuticas disponibles en adicción a la cocaína. Aprovechando la tecnología de IBM, que facilita la integración de servicios cognitivos en la nube, se ha desarrollado una plataforma web que cumple dos funciones: (1) almacenar la información de cada expediente de forma precisa y homogénea; (2) mediante un modelo predictivo basado en dicha información, estimar la probabilidad de éxito de un paciente (entendida como la probabilidad de completar el tratamiento), evitando así el consumo inadecuado de recursos asistenciales

Proyecto PREDIRCAM 2. Análisis preliminar de uso y valoración de la plataforma

En la actualidad, la prevalencia de las enfermedades no transmisibles (Non-communicable diseases NCD) y la cantidad de muertes causadas por éstas es muy elevada, en su mayoría, consecuencia del envejecimiento de la población, el aumento de la obesidad y los hábitos de vida sedentarios. En este trabajo se describen el funcionamiento y los resultados preliminares del proyecto Predircam 2, destinado al desarrollo y validación de una plataforma inteligente de tecnologías biomédicas para la monitorización, prevención y tratamiento personalizados del sobrepeso, la obesidad y la prevención de enfermedades asociadas como la diabetes, hipertensión arterial o alteraciones del metabolismo lipídico. El objetivo de este trabajo es presentar los resultados preliminares del análisis del uso de la plataforma, la evaluación de la usabilidad y la valoración de la atención recibida por los pacientes en relación a los profesionales sanitarios

Microbiome network analysis in skin and gills of Sparus aurata fed with Nannochloropsis gaditana microalgae

1416 and 694 ASVs in gills and skin respectively were preserved in the taxonomic analysis after filtering. The predominant phylum in gills was Proteobacteria (~50%) in the control and hydrolyzed groups and reached 70.58% in the raw diet. The Bacteroidota phylum was the most represented and Firmicutes and Actinobacteria were close to 3% in all treatments in this tissue. However, in all three different treatments, the phyla abundance was similar in skin samples, ~90% of which corresponded to Proteobacteria. Bateroidota (5.5%–5.9%), Firmicutes (1.8%–2%) and Actinobacteria (<1%) constitute the other phyla. In gills, 13 significantly higher ASVs were obtained in the control (such as Achromobacter, Acidobacter) versus 4 whose abundance was higher in the hydrolyzed diet. The number of ASVs that differed significantly between the gill microbiota in the control vs. raw group amounted to 70, most of them being ASVs corresponding to the genus Shewanella (43) higher in the raw diet. Nevertheless, in the skin samples, Control group showed a significant increase of abundance related to Acinetobacter, Achromobacter, Pseudomonas, Shewanella, Vibrio and Sphingomonas among others. In the hydrolyzed group, the most significant abundance was associated with the genus Pseudomonas, Vibrio, Pseudoalteromonas, Ralstonia o Cutibacterium. In the case of the skin raw samples, there were ASVs corresponding to the genus Acinetobacter, Streptococcus or Pseudoalteromonas that were significantly different respect of control. Taking ASV abundance matrix for each diet and tissue, 6 co-occurrence networks were constructed. In all treatments in gills, Acinetobacter was a central genus in the network, and exhibited a negative correlation with Polaribacter. Besides, in the raw group, Polaribacter also showed negative correlation with Aeromonas, Pseudomonas and Francisellacea. This work shows that Acinetobacter has a key role in the balance of mucosa microbiota and was in co-exclusion with Polaribacter.This work was funded by research projects for young researchers, CEIMAR 2019 (Evaluation of hydrolysates of Nannochloropsis gaditana for use in high value-added finishing feed for farmed gilthead sea bream (Sparus aurata) (NAN2BREAM))