Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma.This work was supported by a generous gift from the Dabbiere family (J.F.C.), the Hana Jabsheh Research Initiative (J.F.C.), NIH grant NCI P50CA097257 (J.F.C. and J.A.D.), NCI P01CA118816-06 (J.F.C.), T32 GM008568 and T32 CA151022 (A.M.), and NCI R01CA163336 (J.S.S.), and the Sontag Foundation Distinguished Scientist Award (J.S.S.). C.F. is supported by a US NIH K99/R00 Pathway to Independence Award (K99GM118909) from the National Institute of General Medical Sciences. Additional support was provided by Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (A.X.-M.) and IF/00601/2012 (B.M.C.). J.A.D. is an investigator of the Howard Hughes Medical Institute.info:eu-repo/semantics/publishedVersio

Experimental and computational studies on biomass gasification in fluidized beds

The world’s energy consumption is increasing, and research regarding utilization of renewable energy sources is crucial. Biomass for direct heating has been used for thousands of years, while in the last decades alternative ways to exploit biomass have emerged. In order to increase the efficiency and to produce more applicable products, gasification of biomass is becoming a more and more promising technology. For the gasification technology to be competitive, the understanding of the various aspects regarding the gasifier operation, which in turn influences the quality of the product gas, is of utmost importance. The main objective of this work is to investigate the effect of the air to biomass ratio on the produced gas composition in terms of the high-energy components H2, CH4 and CO. Experiments were performed with wood chips in a pilot scale gasification reactor. The results show that an air-to-biomass ratio less than one gives the most applicable gas composition. Biomass, like wood chips, has a peculiar shape, has a large particle size, is cohesive, and is therefore difficult to fluidize. In a fluidized bed gasifier, a bed material is used to improve the fluidization quality. Experiments were carried out in a cold bed model to study the fluidization properties of the bed material. Minimum fluidization velocities were predicted based on pressure drop in the be