Amplified and Homozygously Deleted Genes in Glioblastoma: Impact on Gene Expression Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. [Methodology]: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. [Principal Findings]: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. [Conclusions]: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.This work was partially supported by Fundação para a Ciência e a Tecnologia, Portugal [FCT PIC/IC/83108/2007]; PhD fellowships from Fundação para a Ciência e a Tecnologia, Portugal [SFRH/BD/23086/2005, SFRH/BD/11820/2003]; Fundación Mutua Madrileña, Madrid, Spain [AP87692011]; and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain [RTICC RD06/0020/0035].Peer Reviewe

Teaching-life Histories: An Analysis of Initial and Continuing Training for Twenty-first century Teachers

This research analyses the teaching practice of retired teachers with the objective of inquiring into the initial and continuing training that twenty-first century teachers need. To this end, a semistructured interview was conducted with an incidental, nonprobabilistic sample of 325 participants and performed quantitative analysis of the data with SPSS 23. The descriptive parameters were produced using frequency analysis. Contingency tables were produced to verify if sex or year of birth explained perceptions of the training required of to be a good teacher. The results revealed significant differences between those born before 1948 and those born after that year

Association between inflammatory infiltrates and isolated monosomy 22/del(22q) in meningiomas

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69+ lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69+, CD63+, CD16+ and CD33+ cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.This work was partially supported by grants from the Fundação para a Ciência e Tecnologia (PIC/IC/83108/2007, FCT, Portugal), Fondo de Investigaciones Sanitarias (FIS/FEDER 06/0312 and RETICC RD06/0020/0035, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain), Caja Burgos (Spain), and Fundación MMA (exp 75312010 and 87692011, Madrid, Spain). Patrícia Domingues is supported by grant (SFRH/BD/64799/2009) from FCT. Maria Dolores Tabernero is supported by IECSCYL (Soria, Spain).Peer Reviewe

Algoritmo Evolutivo Multi-Objectivo para la Toma de Decisiones Interactiva en Optimización Dinámica

Debido al creciente interés en el análisis de datos en streaming en entornos Big Data para la toma de decisiones, cada vez es más común la aparición de problemas de optimización dinámica que involucran dos o más objetivos en conflicto. Sin embargo, los enfoques que combinan optimización dinámica multi-objetivo con la articulación de preferencias para la toma de decisiones son todavía escasos. En este artículo, proponemos un nuevo algoritmo de optimización dinámica multi-objetivo llamado InDM2, que permite incorporar preferencias del experto (humano) de cara a la toma de decisiones para guiar el proceso de búsqueda. Con InDM2, el decisor no solo puede expresar sus preferencias mediante uno o más puntos de referencia (que definen la la región de interés deseada), sino que estos puntos también se pueden modificar de manera interactiva. La propuesta incorpora métodos para mostrar gráficamente las diferentes aproximaciones de la región de interés obtenidas durante el proceso de optimización. El decisor puede así inspeccionar y cambiar, en tiempo de optimización, la región de interés de acuerdo con la información mostrada. Las principales características de InDM2 son descritas y se analiza su funcionamiento mediante casos de uso académicos.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A Methodology for Biplots Based on Bootstrapping with R

A biplot is a graphical representation of two-mode multivariate data based on markers for rows and columns often provided in a two-dimensional space. These markers define parameters that help to interpret goodness of fit, quality of the representation and variability and relationships between variables. However, such parameters are estimated as point values by the biplot, thus no information on the accuracy of the corresponding estimators is obtained. We propose a graphical methodology, that may be considered as an inferential version of a biplot, based on bootstrap confidence intervals for the mentioned parameters. We implement our methodology in an R package and validate it with simulated and real-world data.Un biplot es una representación gráfica de datos multivariantes de dos vías basada en marcadores para filas y columnas proporcionada usualmente en un espacio bidimensional. Estos marcadores definen parámetros que ayudan a interpretar bondad de ajuste, calidad de representación y variabilidad y relaciones entre variables. Sin embargo, tales parámetros son estimados puntualmente en el biplot, sin proporcionar información acerca de la precisión de los estimadores. Se propone una metodología gráfica, que puede ser considerada como una versión inferencial de un biplot, basada en intervalos de confianza bootstrap para los parámetros mencionados. La metodología es implementada en un paquete R y validada con datos simulados y reales

Assessment of hydrocarbon pollution in NW Iberian Peninsula using bioaccumulation and molecular biomarkers in Mytilus galloprovincialis

Society of Environmental Toxicology and Chemistry - SETAC Europe 15th Annual Meeting, Lille, France, May 2005.Polycyclic aromatic hydrocarbons (PAH´s) are ubiquitous contaminants in marine environment as a result of uncontrolled spills, river transport, surface runoff and atmospheric deposition. A significant amount of industrial activity including shipping and oil refining is located along the NW Iberian Peninsula coast. The use of exposure biomarkers holds out promise due to the incipient state of the cost-effective methodologies for diagnosis and monitoring of oil pollution. This work presents the preliminary results concerning the identification of a set of biomarkers for an early warning detection of PAH toxicity. The bivalve Mytillus galloprovincialis was selected due to its ubiquitous distribution along coastline, being used as sentinels in pollution monitoring. This species has also an important value. Four locations in the vicinity of industrial wastewater discharges along the NW Iberian coast were selected and compared with a nearby (reference) site for (i) measurements of PAH body burdens and (ii) levels of enzyme activity: catalase (CAT), superoxide-dismutase (SOD), glutathione peroxidase (GPx), gluthathione S-transferase (GST) and Na+/K+ATPase (ATPase). The results will be discussed on the basis of their potential in providing additional evidence for discriminate between well known polluted and unpolluted sites

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region – either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER)