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

Trigo y política: El proteccionismo cerealista en el Parlamento, 1886-1890

This paper studies the channels through which the agrarian crisis (1886-1890) arrived in the Spanish Parliament and, once there, centered the economic debate until an increase of protectionism was passed.The analysis of the roll-call votes on agrarian customs that took place in those years allows to identify, narrative and quantitatively, the line-up of congressmen according to partisan guides, but, also, according to the economic interests, agrarian interests here, of the provinces that they represented. Interestingly, the Parliamentary dynamics that the agrarian crisis revealed supports the idea of those who see in the Bourbon Restauration a regime where decision-making resulted from the interaction between the economic and political powers. © 2021 The Author(s)The analysis of the roll-call votes on agrarian customs that took place in those years allows to identify, narrative and quantitatively, the line-up of congressmen according to partisan guides, but, also, according to the economic interests, agrarian interests here, of the provinces that they represented. Interestingly, the Parliamentary dynamics that the agrarian crisis revealed supports the idea of those who see in the Bourbon Restauration a regime where decision-making resulted from the interaction between the economic and political powers

Optical constants of Cu2ZnGeS4 bulk crystals

The dielectric functions of Cu2 ZnGeS4 bulk crystals grown by the Bridgman method were measured over the energy range 1.4 to 4.7 eV at room temperature using variable angle spectroscopic ellipsometry. The observed structures in the dielectric functions were adjusted using the Adachi's model and attributed to interband transitions E0, E1A, and E1B at :(000), N (A):2π /a (0.5 0.5 0.5), and T (Z):2π /a (0 0 0.5) points of the first Brillouin zone, respectively. The model parameters (threshold energy, strength, and broadening) have been determined using the simulated annealing algorithm. The decrease in the first gap, E0, has been attributed to a higher Ge-S hybridization. The spectral dependence of the complex refractive index, the absorption coefficient, and the normal-incidence reflectivity were also derived. © 2010 American Institute of Physics.Peer Reviewe

Contributions on lindane degradation by Microcystis aeruginosa PCC 7806

Cyanobacteria are able to tolerate, and even metabolize, moderate doses of organochlorine pesticides, such as lindane (¿-hexachlorocyclohexane), one of the most persistent and widely used in recent decades. Previous work showed that Microcystis aeruginosa PCC 7806 degrades lindane and that, in the presence of the pesticide, microcystin synthesis is enhanced. In this work, using in silico approaches, we have identified in M. aeruginosa putative homologues of the lin genes, involved in lindane degradation in Sphingobium japonicum UT26S. Real-time RT-PCR assays showed that the putative linC gene was induced in the presence of 7 mg/L of lindane. Additionally, prxA, encoding a peroxiredoxin, and involved in oxidative stress response, was also induced when lindane was present. Taking into account these results, M. aeruginosa PCC 7806 may degrade lindane through a metabolic pathway involving a putative 2, 5-dichloro-2, 5-cyclohexadiene-1, 4-diol dehydrogenase encoded by a linC homologue. However, the low similarity of the other potential lin homologues suggest the existence of an alternative pathway different to that of heterotrophic microorganisms such as S. japonicum

Viure amb càncer colorectal

Treballs d'Educació Farmacèutica als ciutadans. Unitat Docent d'Estades en Pràctiques Tutelades. Facultat de Farmàcia, Universitat de Barcelona. Curs: 2015-2016. Tutors: Jordi Casas Sánchez i Marian March Pujol

In silico and In vitro analysis of MAP3773c protein from Mycobacterium avium subsp. Paratuberculosis

Paratuberculosis is a disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). It is of great interest to better understand the proteins involved in the pathogenicity of this organism in order to be able to identify potential therapeutic targets and design new vaccines. The protein of interest–MAP3773c–was investigated, and molecular modeling in silico, docking, cloning, expression, purification, and partial characterization of the recombinant protein were achieved. In the in silico study, it was shown that MAP3773c of MAP has 34% sequence similarity with Mycobacterium tuberculosis (MTB) FurB, which is a zinc uptake regulator (Zur) protein. The docking data showed that MAP3773c exhibits two metal-binding sites. The presence of structural Zn2+ in the purified protein was confirmed by SDS-PAGE PAR staining. The purification showed one band that corresponded to a monomer, which was confirmed by liquid chromatography–mass spectrometry (LC-MS). The presence of a monomer was verified by analyzing the native protein structure through BN-SDS-PAGE (Native Blue (BN) Two-Dimensional Electrophoresis) and BN–Western blotting. The MAP3773c protein contains structural zinc. In conclusion, our results show that MAP3773c displays the features of a Fur-type protein with two metal-binding sites, one of them coordinating structural Zn2+

Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons

Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton