Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial

PURPOSE: The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma. EXPERIMENTAL DESIGN: We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival.RESULTS: Of patients' samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment.CONCLUSIONS: Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.</p

Environmentally induced changes in antioxidant phenolic compounds levels in wild plants

[EN] Different adverse environmental conditions cause oxidative stress in plants by generation of reactive oxygen species (ROS). Accordingly, a general response to abiotic stress is the activation of enzymatic and non-enzymatic antioxidant systems. Many phenolic compounds, especially flavonoids, are known antioxidants and efficient ROS scavengers in vitro, but their exact role in plant stress responses in nature is still under debate. The aim of our work is to investigate this role by correlating the degree of environmental stress with phenolic and flavonoid levels in stress-tolerant plants. Total phenolic and antioxidant flavonoid contents were determined in 19 wild species. Meteorological data and plant and soil samples were collected in three successive seasons from four Mediterranean ecosystems: salt marsh, dune, semiarid and gypsum habitats. Changes in phenolic and flavonoid levels were correlated with the environmental conditions of the plants and were found to depend on both the taxonomy and ecology of the investigated species. Despite species-specific differences, principal component analyses of the results established a positive correlation between plant phenolics and several environmental parameters, such as altitude, and those related to water stress: temperature, evapotranspiration, and soil water deficit. The correlation with salt stress was, however, very weak. The joint analysis of all the species showed the lowest phenolic and flavonoid levels in the halophytes from the salt marsh. This finding supports previous data indicating that the halophytes analysed here do not undergo oxidative stress in their natural habitat and therefore do not need to activate antioxidant systems as a defence against salinity.This work has been funded by the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund. Thanks to Dr. Rafael Herrera for critical reading of the manuscript.Bautista, I.; Boscaiu, M.; Lidón, A.; Llinares Palacios, JV.; Lull, C.; Donat-Torres, MP.; Mayoral García-Berlanga, O.... (2016). Environmentally induced changes in antioxidant phenolic compounds levels in wild plants. Acta Physiologiae Plantarum. 38(1):1-15. https://doi.org/10.1007/s11738-015-2025-2S115381Agati G, Biricolti S, Guidi L, Ferrini F, Fini A, Tattini M (2011) The biosynthesis of flavonoids is enhanced similarly by UV radiation and root zone salinity in L. vulgare leaves. 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Sterility and Gene Expression in Hybrid Males of Xenopus laevis and X. muelleri

BACKGROUND: Reproductive isolation is a defining characteristic of populations that represent unique biological species, yet we know very little about the gene expression basis for reproductive isolation. The advent of powerful molecular biology tools provides the ability to identify genes involved in reproductive isolation and focuses attention on the molecular mechanisms that separate biological species. Herein we quantify the sterility pattern of hybrid males in African Clawed Frogs (Xenopus) and apply microarray analysis of the expression pattern found in testes to identify genes that are misexpressed in hybrid males relative to their two parental species (Xenopus laevis and X. muelleri). METHODOLOGY/PRINCIPAL FINDINGS: Phenotypic characteristics of spermatogenesis in sterile male hybrids (X. laevis x X. muelleri) were examined using a novel sperm assay that allowed quantification of live, dead, and undifferentiated sperm cells, the number of motile vs. immotile sperm, and sperm morphology. Hybrids exhibited a dramatically lower abundance of mature sperm relative to the parental species. Hybrid spermatozoa were larger in size and accompanied by numerous undifferentiated sperm cells. Microarray analysis of gene expression in testes was combined with a correction for sequence divergence derived from genomic hybridizations to identify candidate genes involved in the sterility phenotype. Analysis of the transcriptome revealed a striking asymmetric pattern of misexpression. There were only about 140 genes misexpressed in hybrids compared to X. laevis but nearly 4,000 genes misexpressed in hybrids compared to X. muelleri. CONCLUSIONS/SIGNIFICANCE: Our results provide an important correlation between phenotypic characteristics of sperm and gene expression in sterile hybrid males. The broad pattern of gene misexpression suggests intriguing mechanisms creating the dominance pattern of the X. laevis genome in hybrids. These findings significantly contribute to growing evidence for allelic dominance in hybrids and have implications for the mechanism of species differentiation at the transcriptome level

Patterned self-assembly of gold nanoparticles on chemical templates fabricated by soft UV nanoimprint lithography

Chemical templates for the patterned immobilization of gold nanoparticles were fabricated by soft UV nanoimprint lithography. The template structures were fabricated by means of the consecutively performed process steps of nanoimprint lithography, reactive ion etching, chemical functionalization with amino groups, and lift-off of imprint resist. These chemical templates were used for the defined assembly of 20 nm diameter citrate stabilized gold nanoparticles from aqueous solution. By reducing the ionic strength of the solution, one- and zero-dimensional particle assemblies were generated on sub-100-nm template structures. By this means, the pattern resolution predefined by the lithography process could be easily enhanced by dilution of the nanoparticle solution