Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). in order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions

Low‐temperature sintering of microwave ceramics with high Qf

Microwave ceramic with low‐sintering temperature is one of the most important classes of material to realize the integration and miniaturization of microwave devices. In this work, in order to simultaneously realize low‐temperature sintering and good microwave dielectric properties, CaMgSi2O6–xLiF was sintered at various sintering temperatures using LiF as a sintering aid. In comparison to CaMgSi2O6 (x = 0) sintered at 1250°C, desirable microwave dielectric properties of εr = 7.45, Qf = 64 800 GHz, and τf = −34 ppm/°C and good chemical compatibility with the Ag electrodes, were achieved sintered at 900°C when adding 2 wt% LiF into CaMgSi2O6. Furthermore, a secondary phase, Li2MgSiO4, occurred at x ≥ 1 wt%, and the densest microstructure was obtained at the x value of ~2 wt%. We propose that the high Qf value and the low‐sintering temperature were obtained through moderate LiF addition, which promotes densification and provides Li as the acceptor dopant. By further verifying in Mg2SiO4 ceramic, our study demonstrates that the approach of adding LiF can realize low‐temperature sintering without jeopardizing the excellent microwave dielectric properties, and can potentially be applied in a wide range of low‐temperature sintering of electronic ceramics.Ministry of Education (MOE)Accepted versionSpecial Projects on Science and Technology of Guizhou Province, Grant/ Award Number: [2016]3011; National Key Research and Development Plan, Grant/Award Number: 2016YFA0300801; Academic Research Fund Tier 1 from Singapore Ministry of Education and Nanyang Assistant Professorship Grant, Grant/Award Number: RG108/17; Science and Technology Department of Sichuan Province, Grant/Award Number: 2015JQ0031, 2016JQ0016; National Natural Science Foundation of China, Grant/Award Number: 51772047, 61471096, 6177110