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

Cerium-reduction-induced defects clustering, ordering, and associated microstructure evolution in yttrium-doped ceria

The microstructure, local chemistry, and related evolution of yttrium-doped ceria (YDC) in a reducing environment have been comprehensively characterized by means of electron microscopy and electron energy loss spectroscopy. Long-range ordered features (i.e., superstructures) appear in 25 atom % YDC sintered at high temperature. By combining experimental and atomistic simulation techniques, the ordered structures of defect clusters containing reduced Ce3+ and associated charge-compensating oxygen vacancies have been elucidated. Related microstructure evolution has thereby been explained in terms of the development of ordered defect clusters. In addition, the corresponding diffraction patterns of long-range ordered defect structures embedded in a fluorite lattice have been simulated according to this model, which perfectly matches with experimental diffraction patterns. Such microstructural evolution accompanied by highly ordered defect structures is believed to have strong influence on the ionic conductivity and overall performance of solid oxide fuel cells

Sodium Chloride-Induced leaf senescence in Hydrocotyle bonariensis Lam. and Foeniculum vulgare L.

Leaf senescence induced by sodium chloride was studied in Hydrocotyle bonariensis Lam. and Foeniculum vulgare L. Both species belong to Umbelliferae family, however only H. bonariensis grows spontaneously in sandy soils of coastal regions (saline soils). Leaves of plants receiving nutrient solutions containing different concentrations of NaCl were evaluated for fresh and dry weights and chlorophyll content. The denaturating electrophoretic profiles of leaf proteins were also studied. Sodium chloride changed the protein profile of F. vulgare and hastened the leaf senescence of both the species. However, plants of H. bonariensis receiving 599 mM NaCl lasted longer than F. vulgare. Therefore, the occurrence of H. bonariensis in saline soils might be related with mechanisms of salinity tolerance.<br>Foi estudada a senescência de folhas, induzida por cloreto de sódio, em Hidrocotyle bonariensis Lam. e Foeniculum vulgare L. Ambas as espécies pertencem à família Umbellifera. Contudo, somente H. bonariensis cresce espontaneamente em solos arenosos da região costeira (solos salinos). Foram verificadas a massa fresa, massa seca e concentração de clorofila de folhas de plantas recebendo soluções de NaCl com diferentes concentrações. O perfil eletroforético denaturante de proteínas das folhas também foi avaliado. Aplicação de cloreto de sódio levou a alterações no perfil protéico de F. vulgare e acelerou a senescência das folhas das duas espécies. Todavia, plantas de H. bonariensis recebendo soluções de NaCl com 599 mM sobreviveram mais tempo que as de F. vulgare. Assim a ocorrência de H. bonariensis em solos salinos pode estar relacionada a mecanismos de tolerância à salinidade