Master Regulators, Regulatory Networks, and Pathways of Glioblastoma Subtypes

Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM samples are classified into subtypes based on their transcriptomic and epigenetic profiles. Despite numerous studies to better characterize GBM biology, a comprehensive study to identify GBM subtype-specific master regulators, gene regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute master regulators and gene regulatory networks for each GBM subtype. We also ran Gene Set Enrichment Analysis and Ingenuity Pathway Analysis on GBM expression dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype-specific pathways. Our analysis was able to recover some of the known master regulators and pathways in GBM as well as some putative novel regulators and pathways, which will aide in our understanding of the unique biology of GBM subtypes

Cardiac Autonomic Functions in Obese Children

Objective: The autonomic nervous system is assumed to have a role in the pathophysiology of obesity. In this study, we evaluated the autonomic system by measuring heart rate variability (HRV) in obese children

Correction to “Master Regulators, Regulatory Networks, and Pathways of Glioblastoma Subtypes”

Roll 184a. Klubertanz / Ginger Lee / Chris Keeler. Image 14 of 42. (19 April, 1955) [PHO 1.184a.20]The Boleslaus Lukaszewski (Father Luke) Photographs contain more than 28,000 images of Saint Louis University people, activities, and events between 1951 and 1970. The photographs were taken by Boleslaus Lukaszewski (Father Luke), a Jesuit priest and member of the University's Philosophy Department faculty

Effect of tray dryer’s independent variables (drying temperature and air velocity) on the quality of olive pomace and system’s energy efficiency

[EN] In this study, the effects of drying temperature (70, 80, 90°C) and air velocity (0.5, 1.8 m/s) of hot air drying (tray drying) on quality of dried 2-phase olive pomace and system’s energy efficiency were investigated. The drying experiments were carried out in a tray dryer. The effects of drying conditions were evaluated with analyzing drying time, the primary and secondary oxidation and calculating specific moisture extraction rate (SMER), moisture extraction rate (MER) and specific energy consumption (SEC). The results showed that increase in drying temperature and decrease in air velocity led to decrease in quality of dried olive pomace.Baysan, U.; Koç, M.; Güngör, A.; Kaymak-Ertekin, F. (2018). Effect of tray dryer’s independent variables (drying temperature and air velocity) on the quality of olive pomace and system’s energy efficiency. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1005-1012. https://doi.org/10.4995/IDS2018.2018.7719OCS1005101

Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells

In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient\u27s tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing

Age-Specific Signatures of Glioblastoma at the Genomic, Genetic, and Epigenetic Levels

Age is a powerful predictor of survival in glioblastoma multiforme (GBM) yet the biological basis for the difference in clinical outcome is mostly unknown. Discovering genes and pathways that would explain age-specific survival difference could generate opportunities for novel therapeutics for GBM. Here we have integrated gene expression, exon expression, microRNA expression, copy number alteration, SNP, whole exome sequence, and DNA methylation data sets of a cohort of GBM patients in The Cancer Genome Atlas (TCGA) project to discover age-specific signatures at the transcriptional, genetic, and epigenetic levels and validated our findings on the REMBRANDT data set. We found major age-specific signatures at all levels including age-specific hypermethylation in polycomb group protein target genes and the upregulation of angiogenesis-related genes in older GBMs. These age-specific differences in GBM, which are independent of molecular subtypes, may in part explain the preferential effects of anti-angiogenic agents in older GBM and pave the way to a better understanding of the unique biology and clinical behavior of older versus younger GBMs

Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.

Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation