Exploration of the Activation Mechanism of the Epigenetic Regulator MLL3: A QM/MM Study

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transfer reaction. Our finding suggests that the source of the activation mechanism comes from conformational restriction mediated by the formation of a network of salt-bridges between MLL3 and one of the activating subunits, which restricts and stabilizes the positioning of several residues relevant for the catalysis. New insights into the deprotonation mechanism of lysine are provided, identifying a valine residue as crucial in the positioning of the water molecule in charge of the process. Finally, a tyrosine residue was found to assist the methyl transfer from SAM to the target lysine

Polimorfismo C677T del gen Metilentetrahidrofolato Reductasa como posible factor de riesgo materno para la presentación de síndrome de Down en la población guayaquileña

Objetivo: evaluar la presencia del polimorfismo C677T del gen de la enzima MTHFR como posible factor de riesgo materno para la presentación de síndrome de Down, en la población guayaquileña. Metodología: se realizó un estudio de casos y control que incluyó 51 madres de niños o niñas con síndrome de Down y 52 mujeres que tuvieron en su último embarazo un producto de cualquier sexo sano. Se recolectaron muestras de sangre venosa periférica entre los meses de diciembre 2010 y mayo 2011 posteriora lo que se realizó extracción de ADN y genotipificación del polimorfismo C677T del gen de la enzima MTHFR. Para el análisis estadístico se utilizó Chi cuadrado de Pearson (X2), odds ratio (OR) con intervalo de confianza de 95% (95%IC). Valores de p<0.05 fueron considerados estadísticamente significativos. Resultados: se incluyeron 51 mujeres madres de hijos/as con síndrome deDown y 52 madres control. La frecuencia del alelo T fue mayor en el grupo casos (X2=0.944, p=0.331). En el análisis simultáneo de las variantes genotípicas heterocigota y homocigota del gen MTHFR 677 (CT y TT) en los grupos casos y control, no se observó aumento de riesgo para el síndrome (OR=0.87 [IC 95% 0.34 – 2.20]; p=0.772). Conclusión: no se encontró relación entre la presenciadel polimorfismo C677T MTHFR y aumento en el riesgo materno para síndrome de Down. Es necesario realizar mayores investigaciones en la población ecuatoriana en general que determinen la asociación de diversos polimorfismos en diferentes genes

PISA 2012 : primeros resultados. Informe Nacional del Perú

El presente documento se presenta al país para contribuir con la difusión de los resultados de la ronda 2012 del Programa Internacional para la Evaluación de Estudiantes (PISA, por sus siglas en inglés) de la Organización para la Cooperación y el Desarrollo Económico (OCDE). Este documento contiene la información principal que muestra el desempeño del Perú en este estudio, así como (en los casos en los que es posible) una observación de los cambios acontecidos en el período desde que se inició el programa (2000). El primer capítulo brinda información general acerca del programa PISA. La misma es relevante y necesaria para entender el alcance de los resultados, es decir, para definir con precisión qué es posible y qué no es posible decir con la información existente. El segundo capítulo se aboca a presentar los resultados peruanos en la evaluación conducida en 2012. Como referencia, se utilizará los valores típicos observados en los países de la OCDE, así como en los demás países latinoamericanos que participan en PISA. El tercer capítulo muestra los cambios en el desempeño lector ocurridos en el Perú entre los años 2000 y 2012. Como en el caso anterior, se hará uso de información comparativa de otros países como referencia. El cuarto capítulo se abocará a observar la importancia de los antecedentes socioeconómicos de los estudiantes en su desempeño como una forma clave para identificar posibles problemas vinculados a la equidad en el sistema educativo. Por último, se presenta un conjunto de comentarios y reflexiones finales acerca de estos primeros resultados

Self-esteem and suicidal behaviour in youth: A meta-analysis of longitudinal studies

Background: Previous literature suggests that low self-esteem is a risk factor for suicide attempts, but no meta-analyses have been conducted to assess this association in adolescents/young adults. The present study examined the relationship between low self-esteem and suicide attempts in young people (12-26 years old). Method: Meta-analyses were performed using random-effects models (ES) and odds ratio (OR). Heterogeneity and sensitivity analyses were performed. Results: From 26,883 initial titles, 22 studies met the inclusion criteria, of which 9 studies had data that could be included in the meta-analysis. The meta-analysis showed that youths with lower self-esteem were more likely to have future suicide attempts, with an effect size (self-esteem as continuous variable) of d = .58 (95% CI = .44 - .73) and, for low self-esteem (categorical variable) an OR = 1.99 (95% CI = 1.39-2.86; p < .001). Conclusion: A low level of self-esteem is a risk factor for suicide attempts in adolescents/young adults

Prevalence of self-harm among lesbian, gay, bisexual, and transgender adolescents: a comparison of personal and social adversity with a heterosexual sample in Ghana

Objectives We sought to estimate the prevalence of self-reported self-harm among adolescents identifying as lesbian, gay, bisexual, and transgender (LGBT) in Ghana, and compare self-reported personal and social adversities related to self-harm in this group to those in a random sample of heterosexual adolescents from the same locality. Results A total of 444 adolescents aged 13-21 years, comprising 74 LGBT adolescents and 370 heterosexual adolescents, provided data. The lifetime prevalence estimate of self-harm was higher in the LGBT group (47%) than the heterosexual group (23%). The LGBT group reported a higher rate of self-harm during the previous 12 months (45%), compared to the heterosexual group (18%). LGBT adolescents reported more alcohol and substance use and more personal social adversities, including various forms of victimisation, than heterosexual adolescents. They were no more likely to report difficulty in making and keeping friends or schoolwork problems than were heterosexual adolescents

Exploration of the Interaction Strength at the Interface of Anionic Chalcogen Anchors and Gold (111)-Based Nanomaterials

Nowadays, the use of sulfur-based ligands to modify gold-based materials has become a common trend. Here, we present a theoretical exploration of the modulation of the chalcogenides-gold interaction strength, using sulfur, selenium, and tellurium as anchor atoms. To characterize the chalcogenide-gold interaction, we designed a nanocluster of 42 gold atoms (Au-42) to model a gold surface (111) and a series of 60 functionalized phenyl-chalcogenolate ligands to determine the ability of electron-donor and -withdrawing groups to modulate the interaction. The analysis of the interaction was performed by using energy decomposition analysis (EDA), non-covalent interactions index (NCI), and natural population analysis (NPA) to describe the charge transfer processes and to determine data correlation analyses. The results revealed that the magnitudes of the interaction energies increase following the order S < Se < Te, where this interaction strength can be augmented by electron-donor groups, under the donor-acceptor character the chalcogen-gold interaction. We also found that the functionalization inmetaposition leads to better control of the interaction strength than theorthosubstitution due to the steric and inductive effects involved when functionalized in this position.Fondo Nacional de Desarrollo Cientifico y Tecnologogico de Chile 1181082 118015

Noncovalent interactions in inorganic supramolecular chemistry based in heavy metals. Quantum chemistry point of view

Complexity is a concept that is being considered in chemistry as it has shown potential to revealinteresting phenomena. Thus, it is possible to study chemical phenomena in a new approachcalled systems chemistry. The systems chemistry has an organization and function, which areregulated by the interactions among its components. At the simplest level, noncovalent interac-tions between molecules can lead to the emergence of large structures. Consequently, it is pos-sible to go from the molecular to the supramolecular systems chemistry, which aims to developchemical systems highly complex through intra- and intermolecular forces. Proper use of theinteractions previously mentioned allow a glimpse of supramolecular system chemistry in manytasks such as structural properties reflecting certain behaviors in the chemistry of materials, forexample, electrical and optical, processes of molecular recognition and among others. In the lasttime, within this area, inorganic supramolecular systems chemistry has been developed. Thosesystems have a structural orientation which is defined by certain forces that predominate in theassociations among molecules. It is possible to recognize these forces as hydrogen bonding,π-πstacking, halogen bonding, electrostatic, hydrophobic, charge transfer, metal coordination, andmetallophilic interactions. The presence of these forces in supramolecular system yields certainproperties such as light absorption and luminescence. The quantum theoretical modeling playsan important role in the designing of the supramolecular system. The goal is to apply supramo-lecular principles in order to understand the associated forces in many inorganic molecules thatinclude heavy metals for instance gold, platinum, and mercury. Relevant systems will be studiedin detail, considering functional aspects such as enhanced coordination of functionalized molec-ular self-assembly, electronic and optoelectronic properties

Quantum chemistry simulation of the electronic properties in [Au(NH3)(2)]NO3 and [Au(NCH)(2)][AuCl4] extended unsupported complexes

The understanding of closed-shell interactions has become of tremendous relevance in the ever-growing field of supramolecular chemistry. Here, we present a theoretical study in which we characterised the intermolecular interactions between gold-based building blocks, namely ([Au(NH3)(2)]NO3)(n) (n = 1,2,4,8) and ([Au(NCH)(2)][AuCl4])(n) (n = 1,2). Due to the complex nature of these interactions, several methods were used such as the MP2, CCSD(T), PBE-D3, B3LYP-D3, and CAM-B3LYP-D3 (DFT-D3) levels. In all models were found closed-shell contacts among the gold atoms, interactions that resulted in being consistent with the presence of a high ionic contribution and a dispersion-type interaction. The absorption spectra of these models were calculated by the single excitation time-dependent-DFT (TD-DFT) method and CC2 levels, being the aurophilic interactions mainly responsible for the bands in both types of models. The theoretical models agree with the experimental results.CONICYT FONDECY

Polimorfismo C677T del gen Metilentetrahidrofolato Reductasa como posible factor de riesgo materno para la presentación de síndrome de Down en la población guayaquileña

Objetivo: evaluar la presencia del polimorfismo C677T del gen de la enzima MTHFR como posible factor de riesgo materno para la presentación de síndrome de Down, en la población guayaquileña. Metodología: se realizó un estudio de casos y control que incluyó 51 madres de niños o niñas con síndrome de Down y 52 mujeres que tuvieron en su último embarazo un producto de cualquier sexo sano. Se recolectaron muestras de sangre venosa periférica entre los meses de diciembre 2010 y mayo 2011 posteriora lo que se realizó extracción de ADN y genotipificación del polimorfismo C677T del gen de la enzima MTHFR. Para el análisis estadístico se utilizó Chi cuadrado de Pearson (X2), odds ratio (OR) con intervalo de confianza de 95% (95%IC). Valores de p<0.05 fueron considerados estadísticamente significativos. Resultados: se incluyeron 51 mujeres madres de hijos/as con síndrome deDown y 52 madres control. La frecuencia del alelo T fue mayor en el grupo casos (X2=0.944, p=0.331). En el análisis simultáneo de las variantes genotípicas heterocigota y homocigota del gen MTHFR 677 (CT y TT) en los grupos casos y control, no se observó aumento de riesgo para el síndrome (OR=0.87 [IC 95% 0.34 – 2.20]; p=0.772). Conclusión: no se encontró relación entre la presenciadel polimorfismo C677T MTHFR y aumento en el riesgo materno para síndrome de Down. Es necesario realizar mayores investigaciones en la población ecuatoriana en general que determinen la asociación de diversos polimorfismos en diferentes genes