scholarly journals Characterisation of the metabolomes of epigenetically distinct subgroups of paediatric ependymoma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv10-iv10
Author(s):  
Alison Woodward ◽  
Salah Abdelrazig ◽  
Catharine Ortori ◽  
David Barrett ◽  
Richard Grundy ◽  
...  

Abstract Paediatric ependymoma relapses in up to half of patients, with a five-year survival rate of only 25%. Comprehensive characterisation of the genetic/epigenetic mutation and transcriptome landscape has not yet translated to improved treatments. Metabolomics is a functional genomic approach, offering an opportunity to elucidate aberrant metabolic pathways and new therapeutic avenues. Metabolomics thus far has concentrated on 1H High-resolution Magic Angle Spinning, Magnetic Resonance Spectroscopy and Raman Spectroscopy, where low numbers of metabolites were identified compared to that feasible by Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS). Here we present broader metabolome coverage using LC-MS/MS to separately analyse ependymoma polar and non-polar metabolites, comparing two subgroups from distinct neuro-anatomical compartments with different genetic and epigenetic drivers. We homogenised surgically resected ependymoma tissue from two epigenetic subgroups, posterior fossa A (n=10) and supratentorial RELA fusion (n=5), and extracted polar metabolites and lipids using methanol/water/chloroform 1:1:3. LC-MS/MS using a quadrupole-Orbitrap revealed 167 putative metabolites and 400 putative lipids significantly altered in relative abundance between the two subgroups. The metabolites predominantly mapped onto the taurine and hypotaurine pathway. Grade II and III PF-A tumours could be distinguished by the abundances of 53 metabolites, with three metabolites in the protein-lysine degradation pathway increased in abundance. The study presents a first-in-kind description of the paediatric ependymoma metabolome revealing PF-A and ST-RELA subgroups are metabolically distinct brain tumours and therefore warrant consideration of distinct anti-metabolite therapies. Paediatric ependymoma intra-tumour regions have been collected from 6 surgical resections and ongoing intra-tumour metabolomics/lipidomics integrated with transcriptomics will be discussed.

2021 ◽  
Vol 2 (1) ◽  
pp. 39-48
Author(s):  
Nguyen H. H. Phuc ◽  
Takaki Maeda ◽  
Tokoharu Yamamoto ◽  
Hiroyuki Muto ◽  
Atsunori Matsuda

A solid solution of a 100Li3PS4·xLi3PO4 solid electrolyte was easily prepared by liquid-phase synthesis. Instead of the conventional solid-state synthesis methods, ethyl propionate was used as the reaction medium. The initial stage of the reaction among Li2S, P2S5 and Li3PO4 was proved by ultraviolet-visible spectroscopy. The powder X-ray diffraction (XRD) results showed that the solid solution was formed up to x = 6. At x = 20, XRD peaks of Li3PO4 were detected in the prepared sample after heat treatment at 170 °C. However, the samples obtained at room temperature showed no evidence of Li3PO4 remaining for x = 20. Solid phosphorus-31 magic angle spinning nuclear magnetic resonance spectroscopy results proved the formation of a POS33− unit in the sample with x = 6. Improvements of ionic conductivity at room temperature and activation energy were obtained with the formation of the solid solution. The sample with x = 6 exhibited a better stability against Li metal than that with x = 0. The all-solid-state half-cell employing the sample with x = 6 at the positive electrode exhibited a better charge–discharge capacity than that employing the sample with x = 0.


1998 ◽  
Vol 62 (2) ◽  
pp. 165-178 ◽  
Author(s):  
C. M. B. Henderson ◽  
A. M. T. Bell ◽  
S. C. Kohn ◽  
C. S. Page

AbstractThe structure of a synthetic end-member wairakite (CaAl2Si4O12·2H2O) has been determined using Rietveld analysis of high-resolution, synchrotron X-ray powder diffraction data, and 29Si and 27Al magic angle spinning nuclear magnetic resonance spectroscopy. The framework in the synthetic sample is more disordered than that in natural wairakite. Ca is distributed over the cavity cation sites M2, M12A, M12B in the approximate proportions 0.8:0.1:0.1, respectively, with M11 being vacant. 29Si MAS NMR data are consistent with about 80% of the Si occupying tetrahedral T11 and T12 sites linked to two Al atoms [Q4(2Al) silicons]. Tetrahedral and cavity cation site disorder are coupled so that Al mainly occupies T2 sites, with Ca in M12A and M12B being balanced by Al in T12A and T12B; T11A and T11B sites appear to only contain Si, in agreement with the M11 site being vacant. The crystal chemistries of the wide range of stoichiometries which crystallize with the leucite/pollucite structure-type are also reviewed, with particular attention being paid to the tetrahedral ordering configurations present in these phases, and the implications to crystallographic phase transitions.


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