More epigenetic hits than meets the eye: microRNAs and genes associated with the tumorigenesis of retinoblastoma

Retinoblastoma (RB), a childhood neoplasia of the retinoblasts, can occur unilaterally or bilaterally, with one or multiple foci per eye. RB is associated with somatic loss of function of both alleles of the tumor suppressor gene RB1. Hereditary forms emerge due to germline loss of function mutations in RB1 alleles. RB has long been the prototypic “model” cancer ever since Knudson's “two-hit” hypothesis. However, a simple two-hit model for RB is challenged by an increasing number of studies documenting additional hits that contribute to RB development. Here we review the genetics and epigenetics of RB with a focus on the role of small non-coding RNAs (microRNAs) and on novel findings indicating the relevance of DNA methylation in the development and prognosis of this neoplasia. Studies point to an elaborated landscape of genetic and epigenetic complexity, in which a number of events and pahtways play crucial roles in the origin and prognosis of RB. These include roles for microRNAs, inprinted loci, and parent-of-origin contributions to RB1 regulation and RB progression. This complexity is also manifested in the structure of the RB1 locus itself: it includes numerous repetitive DNA segments and retrotransposon insertion elements, some of which are actively transcribed from the RB1 locus. Altogether, we conclude that RB1 loss of function represents the tip of an iceberg of events that determine RB development, progression, severity, and disease risk. Comprehensive assessment of personalized RB risk will require genetic and epigenetic evaluations beyond RB1 protein coding sequences

Initial Development toward Non-Invasive Drug Monitoring via Untargeted Mass Spectrometric Analysis of Human Skin.

Drug monitoring is crucial for providing accurate and effective care; however, current methods (e.g., blood draws) are inconvenient and unpleasant. We aim to develop a non-invasive method for the detection and monitoring of drugs via human skin. The initial development toward this aim required information about which drugs, taken orally, can be detected via the skin. Untargeted liquid chromatography-mass spectrometry (LC-MS) was used as it was unclear if drugs, known drug metabolites, or other transformation products were detectable. In accomplishing our aim, we analyzed samples obtained by swabbing the skin of 15 kidney transplant recipients in five locations (forehead, nasolabial area, axillary, backhand, and palm), bilaterally, on two different clinical visits. Untargeted LC-MS data were processed using molecular networking via the Global Natural Products Social Molecular Networking platform. Herein, we report the qualitative detection and location of drugs and drug metabolites. For example, escitalopram/citalopram and diphenhydramine, taken orally, were detected in forehead, nasolabial, and hand samples, whereas N-acetyl-sulfamethoxazole, a drug metabolite, was detected in axillary samples. In addition, chemicals associated with environmental exposure were also detected from the skin, which provides insight into the multifaceted chemical influences on our health. The proof-of-concept results presented support the finding that the LC-MS and data analysis methodology is currently capable of the qualitative assessment of the presence of drugs directly via human skin

Modificaciones fenotípicas por efecto de selección masal estratificada en dos poblaciones braquiticas de maíz

En el Centro Nacional de Investigaciòn Palmira, Instituto Colombiano Agropecuario, se determinó, semestre tras semestre, el avance de la selecciòn masal estratificada por prolificidad y rendimiento en dos poblaciones promisorias de maìz convertidas a braquìticas. Se observò en qué forma ha variado la arquitectura de la planta braquìtica en relación con la variedad original y los diferentes ciclos de selección. La evaluaciòn se hizo durante 1.977-B y 1.978-A con Los materiales básicos MB. 22 (amarillo), MB. 23 (blanco) y nueve ciclos de selección en cada uno de aquellos. Se tomaron datos sobre los siguientes aspectos: rendimiento, prolificidad, floraciOn femenina, estatura de la planta, altura de la mazorca superior, largo de los entrenudos hasta la mazorca superior, dìas hasta la floración y largo por ancho de La hoja de La mazorca superior (indicativo para el àrea foliar). Los resultados mostraron que la selección en las poblaciones convertidas a braquìticas ha sido eficaz para obtener ganancias en rendimiento y prolificidad. En MB. 22 la ganancia fue de 4,3917,, y 3,89%en rendimiento y prolificidad por ciclo de selección (tasas altamente significativas). En MB. 23 la ganancia por ciclo de selección en rendimiento fue de 0,27% (no significativa) y para prolificidad de 2,78% (altamente significativa). Además, se han modificado la estatura de la planta y la altura de la mazorca superior por incrementos debidos al alargamiento y al mayor nùmero de entrenudos por debajo de la mazorca. Los entrenudos son más cortos cerca de la superficie del suelo y su longitud va aumentando a medida que se aproximan a la mazorca superior. El entrenudo de ésta es generalmente el más largo. El rendimiento aumentó aI incrementarse la estatura de la planta y la altura de La mazorca superior. 19 En una de las poblaciones (MB. 22) los dìas hasta la floración femenina y el indicativo del àrea foliar permanecieron constantes mientras que en la otra poblaciòn (MB. 23) se encontraron incrementos bajos aunque estadìsticamente significativos; no obstante, parece que los incrementos de estos caracteres no aportaron a la ganancia en rendimiento.A stratified mass selection procedure was performed in two basic populations of brachytic-2 maize, MB. 22 (yellow) and MB. 23 (white). The selection plots and the test sites were located at the Palmira Experimental Station of [CA (Colombian Agricultural Institute). The two populations and nine cicles of mass selection by prolificacy and yield (MPR) in each were tested during 1.977-13 and 1.978-A cropping seasons. Significant gains per cycle of 4,94% and 4,39% in yield and prolificacy, respectively, were obtained in MB. 22; in MB. 23 the gains were 0,27%and 2,781/o**, respectively. The number of the internodes below the upper ear increased 1 ,24** and 1,33 per cicle of selection MPR in MB. 22 and MB. 23, respectively. The internode length also increased, more in the internodes close to the upper ear (1,72% ** and 1,09% ** in the sixth in MB. 22 and MB. 23 respectively) than in the first one, close to the soil surface. Plant height increased at a rate of 1,70% ** and 1,27% ** per cicle of selection MPR in MB. 22 and MB. 23, respectively. Ear height also increased at 2,44% ** and 2,46% ** in those populations. Other estimates of gain per cycle were, in MB. 22 and MB. 23: Days to flower 0,02% and 0,17%*; I.eaf area 0,05%and 0,5717o *; Ear length 0,20%and -0,22%; Ear diameter 0,15%and -0,6117h The traits most influenced by the prevalent environmental conditions, according to the high expectation of their Cycle x Season mean square in the combined analysis of variance, were days to flower and ear diameter in MB. 22. In MB. 23: yield, ear length, ear diameter and leaf area. All other traits in the cycled generations in both populations were not influenced by those same environmental conditions during the tests.Maíz-Zea may

Isolation and characterization of salt-sensitive mutants of the moderate halophile Halomonas elongata and cloning of the ectoine synthesis genes

The moderate halophile Halomonas elongata Deustche Sommlung fur Mikroorganismen 3043 accumulated ectoine, hydroxyectoine, glutamate, and glutamine in response to osmotic stress (3 M NaCl). Two Tn1732-induced mutants, CHR62 and CHR63, that were severely affected in their salt tolerance were isolated. Mutant CHR62 could not grow above 0.75 M NaCl, and CHR63 did not grow above 1.5 M NaCl. These mutants did not synthesize ectoine but accumulated ectoine precursors, as shown by 13C NMR and mass spectroscopy. Mutant CHR62 accumulated low levels of diaminobutyric acid, and mutant CHR63 accumulated high concentrations of N-γ-acetyl-diaminobutyric acid. These results suggest that strain CHR62 could be defective in the gene for diaminobutyric acid acetyltransferase (ectB), and strain CHR63 could be defective in the gene for the ectoine synthase (ectC). Salt sensitivity of the mutants at 1.5-2.5 M NaCl could be partially corrected by cytoplasmic extracts of the wild-type strain, containing ectoine, and salt sensitivity of strain CHR62 could be partially repaired by the addition of extracts of strain CHR63, which contained N-γ-acetyldiaminobutyric acid. This is the first evidence for the role of N-γ-acetyldiaminobutyric acid as osmoprotectant. Finally, a cosmid from the H. elongata genomic library was isolated which complemented the Ect- phenotype of both mutants, indicating that it carried at least the genes ectB and ectC of the biosynthetic pathway of ectoin

Evaluación de la selección h, mediante hermanos completos y su síntesis, para resistencia a diatraea spp. de dos variedades de maíz

El criterio de selección fue el menor número de orificios de salida del insecto, en pares de plantas, hembra y macho, éstas, últimas también auto polinizadas. En infestación natural, se estudió el efecto del sistema de selección en el daño causado por el insecto, y en los caracteres correlacionados: rendimiento, días a floración femenina, prolificidad, altura de mazorca y estatura de planta. Se determinó el avance por ciclo de selección para cada uno de estos caracteres por el método de la regresión, tomando el porcentaje relativo de cada carácter con respecto a la variedad original, para cada uno de los niveles de síntesis en las dos variedades. Se obtuvieron materiales derivados en los que aparentemente se fueron acumulando genes para otros caracteres relacionados con rendimiento.An evaluation of the H selection, through full-sib in them and their synthesis, was carry out, for resistance to Diatraea spp., in two corn varieties (ETO and DIACOL V. 351). The judgment of selection was the less number of holes from the insect exit, in pairs of plants, male and female, these last ones self pollennized. Under natural infestation, the effect of the selection system was studied in the damage caused by the insect, and in the correlate yield character, the femenine floration days, prolificity, ear corn height and plant stature. The advance was determined by the selection cycle of each one ot these characters under the regretion method, taking a relative percentage of each character in respect to the original variety, for each one of the synthesis level. Derived materials were obtained in which genes for the resistance to Diatraea spp., apparently were acumulated, and indirectly genes were qathered for other characters related to the yielding

Use of educational robotics as a stimulus to creativity

The present research aims to stimulate the creativity of young people through educational robotics. Results of three workshops carried out in an innovation laboratory of a higher education institution with members of a social project from 13 to16 years old are presented. Participants were challenged to solve problems related to educational robotics using Scratch and Arduino, with the proposed theme being traffic education. The results will be presented according to the following categories of analysis: use of unusual solutions for problem solving, level of intrinsic motivation, and use of organized and procedural thinking

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press

Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al‑Ándalus project

Candidate-gene studies on fibromyalgia susceptibility often include a small number of single nucleotide polymorphisms (SNPs), which is a limitation. Moreover, there is a paucity of evidence in Europe. Therefore, we compared genotype frequencies of candidate SNPs in a well-characterised sample of Spanish women with fibromyalgia and healthy non-fibromyalgia women.This work was supported by the Spanish Ministry of Economy and Competitiveness [I+D+i DEP2010-15639, I+D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.]; the Spanish Ministry of Education [FPU2014/02518 to M.B.-C.]; the Consejería de Turismo, Comercio y Deporte, Junta de Andalucía [CTCD-201000019242-TRA to M.D.-F.]; Consejería de Salud, Junta de Andalucía [PI-0520-2016 to M.D.-F.], and the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). This work is part of a Ph.D. Thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spai