Inhibition of RNA helicases of ssRNA⁺ virus belonging to <i>Flaviviridae</i>, <i>Coronaviridae</i> and <i>Picornaviridae</i> families

Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families

Arte y cultura popular en Huixquilucan : análisis de una política pública cultural

TrabajoTerminal (Licenciatura en Sociología) -- Universidad Autónoma Metropolitana, Unidad Azcapotzalco, División de Ciencias Sociales y Humanidades, Departamento de Sociología, Área de concentración: Sociología Urbana, 2010. Sinodales: José Othón Quiróz Trejo, María Soledad Cruz Rodríguez. UAMADCSHDS. 1 archivo PDF (95 páginas

Children exposed to intimate partner violence: Identifying differential effects of family environment on children\u27s trauma and psychopathology symptoms through regression mixture models

The majority of analytic approaches aimed at understanding the influence of environmental context on children\u27s socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7–12 years. A regression mixture model identified three latent classes that were primarily distinguished by differential effects of IPV exposure severity on PTS and psychopathology symptoms: (1) asymptomatic with low sensitivity to environmental factors (66% of children), (2) maladjusted with moderate sensitivity (24%), and (3) highly maladjusted with high sensitivity (10%). Children with mothers who had higher levels of education were more likely to be in the maladjusted with moderate sensitivity group than the asymptomatic with low sensitivity group. Latino children were less likely to be in both maladjusted groups compared to the asymptomatic group. Overall, the findings suggest differential effects of family environmental factors on PTS and psychopathology symptoms among children exposed to IPV. Implications for research and practice are discussed

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10⁻⁶). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10⁻¹⁰). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America

Eco-Contribution for the Production of N-Arylnitrones: Solvent-Free and Assisted by Microwaves

A simple green approach for the production of benzylideneaniline oxides is offered. This contribution was performed via the condensation of phenylhydroxylamine with several aryl aldehydes, in the absence of both catalyst and solvent, and using microwave irradiation as the activating reaction mode. In addition, good yields of the products were achieved in a short time. It is also worth noting that the work-up procedure is simple and the products do not require further purification. Finally, an interesting comparison without the use of microwave irradiation is also discussed

[1,2,3]triazolo[4,5-<i>H</i>]chinoloni: una nuova classe di promettenti chemioterapici antitubercolari

Alcuni acidi triazolo[4,5-h] e [4,5-f]chinoloncarbossilici angolari, sintetizzati in precedenza come antiinfettivi del tratto urinario, hanno mostrato interessanti valori di MIC90 nei confronti di M. tuberculosis H37Rv. Allo scopo di approfondire le nostre conoscenze sui rapporti struttura-attività di questa classe, abbiamo pertanto preparato una nuove serie di derivati

Triazolopyridinyl-acrylonitrile derivatives as antimicrotubule agents: Synthesis, in vitro and in silico characterization of antiproliferative activity, inhibition of tubulin polymerization and binding thermodynamics

In this paper we report the synthesis, in vitro anticancer activity, and the experimental/computational characterization of mechanism of action of a new series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g, 7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to interesting antiproliferative activity against 9 different cancer cell lines derived from solid and hematological human tumors. Fluorescence-based assays prove that these molecules interfere with tubulin polymerization. Furthermore, isothermal titration calorimetry (ITC) provides full tubulin/compound binding thermodynamics, thereby ultimately qualifying and quantifying the interactions of these molecular series with the target protein. Lastly, the analysis based on the tight coupling of in vitro and in silico modelling of the interactions between tubulin and the title compounds allows to propose a molecular rationale for their biological activity

Impact of yeast and fungi (1-3)(1-6)- β-glucan concentrates on viscoelastic behavior and bread making performance of gluten-free rice-based doughs

Producción CientíficaThe addition of bioactive β-glucan to gluten-free breads is of special interest to people suffering from celiac disease. Most of the studies found in literature involve cereal (1 → 3)(1 → 4)-β-glucan, while those from yeast and fungi are still nearly unexplored. This study focuses on the effect of fortifying gluten-free rice-based doughs and breads with (1 → 3)(1 → 6)-β-glucan concentrates derived from yeasts –soluble (SBG) and insoluble (IBG)– and fungi (Pleurotus Ostreatus) (FBG). SBG-enriched doughs were less firm and exhibited lower resistance to deformation than doughs with FBG or IBG. In contrast, FBG- and IBG-enriched doughs increased their resistance to deformation as the concentration increased. Doughs with a firmer consistency as determined by a forward extrusion test (FBG- and IBG-enriched doughs) corresponded to those with larger dynamic moduli and lower frequency dependence, lower elastic deformation and higher viscosity at steady state. The physical quality of breads was significantly improved by addition of all types of (1→3)(1→6)-β-glucan at optimized dough hydration. They caused an increase in the specific volume of the breads, a reduction in their hardness and longer shelf-life. Sensory evaluation also demonstrated an improvement in bread organoleptic attributes when SBG was added.Ministerio de Economía, Industria y Competitividad - FEDER (Proyects AGL2012-35088 and AGL2015-63849-C2-2-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA072P17

Letalidad en hospitalizados por neumonía adquirida en la comunidad según antibiótico inicial. Estudio comparativo de dos series de casos

Fundamento: la neumonía adquirida en la comunidad constituye uno de los más importantes problemas de salud a nivel mundial y en el Hospital de Cienfuegos.Objetivo: determinar cambios en el comportamiento de la relación existente entre el tipo de antimicrobiano utilizado empíricamente al ingreso y la letalidad por neumonía adquirida en la comunidad, entre dos series de casos conformadas en momentos diferentes. Métodos: estudio observacional, con diseño descriptivo, en el que fueron comparadas dos series de casos de pacientes hospitalizados por la entidad objeto de estudio. Se analizó la relación existente entre antimicrobianos seleccionados: amoxicilina/sulbactam, cefuroxima, ceftriaxona y cefotaxima, y la letalidad, teniendo en cuenta variables potencialmente confusoras. En el tratamiento estadístico fueron utilizados el estadígrafo Chi2 para diferencias de proporciones, y el test exacto de Fisher, con un nivel de confianza de 95 % (p &lt; .05). Resultados: en ambas series de casos se observó el mismo patrón en cuanto a los antimicrobianos con el menor y con el mayor valor de letalidad: cefuroxima y cefotaxima respectivamente. En cambio, en contraste con la serie A, en la serie B se observó un comportamiento más uniforme de la letalidad entre los distintos antimicrobianos, lo cual significó una disminución ostensible en la letalidad en los tratados inicialmente con cefalosporinas de tercera generación de la serie B. En este sentido, el impacto más evidente lo proporcionó el comportamiento de la letalidad en los pacientes que recibieron ceftriaxona. Conclusiones: la cefuroxima se mantiene como el antimicrobiano empírico inicial relacionado con menor letalidad en pacientes con neumonía adquirida en la comunidad. En la segunda serie de casos se constató una mejoría evidente en la letalidad en los tratados con ceftriaxona y cefotaxima.</p