Search bioRxiv⌕ Search

Biology subjects

Tawil, N.

Publications and source records attributed to Tawil, N..

2 recordsLinked to original sources

Face in the facade: How face-likeness modulates memory and neural representations

Evidence suggests that information represented more reliably in neural activity patterns across repeated exposures is more likely to be remembered. However, this relationship varies across category-selective regions of the ventral visual cortex. Specifically, for house stimuli neural reliability has been robustly linked to memory outcomes in the parahippocampal place area (PPA), but less consistently for faces in the fusiform face area (FFA). The reason for this mismatch is unknown. To address this discrepancy, we implemented a novel within-category manipulation by presenting highly face-like and non-face-like house stimuli during fMRI, followed by a memory test. Non-face-like houses were more likely to be remembered than face-like houses. Although face-likeness did not elicit face-selective responses in the FFA, representational reliability in ventral visual cortices, particularly in the FFA, showed an association with individual differences in memory performance. Finally, symmetry emerged as a potential perceptual factor underlying differences in mnemonic outcomes.

neuroscience↗

Cancer-derived Extracellular Vesicles for Targeted Delivery of EGFRvIII siRNA to Glioblastoma, Comparison of siRNA Loading Methods and Efficiency

BackgroundExtracellular vesicles (EVs) are nano and macro-sized, lipid-bound particles, involved in cellular communication. Interestingly, cancer-derived EVs show a heterologous and cross-species tumour tropism which makes them a potential tool for efficient delivery of therapeutic small interfering RNA (siRNA) to the tumour cells. MethodsEVs derived from glioblastoma cells (U373P and U373vIII) were loaded with EGFRvIII siRNA to develop a targeted therapeutic strategy against glioblastoma. EV biodistribution was evaluated using fluorescent indocyanine green (ICG) staining followed by ex vivo imaging. Different loading strategies, including passive loading, sonication, saponin-mediated membrane permeabilization, electroporation, and transfection were assessed for their efficiency in loading siRNA into EVs. The efficiency of each method was evaluated by nano flowcytometry, in vitro uptake assay followed by immunoblot (western blot) analysis. Eventually, the most effective formulation was tested for the systemic siRNA administration and selective tumour delivery in vivo, followed by evaluation of tumour size and EGFRvIII expression. ResultsHere, we showed that siRNA transfection into EVs was the most effective loading strategy, as confirmed by nano-flow cytometry, uptake assays, and western blot analysis, achieving over 90% knockdown efficiency in vitro for EVs carrying EGFRvIII siRNA. In vivo, EGFRvIII siRNA-loaded EVs homed to the tumour site and downregulated EGFRvIII expression compared with the PBS-siRNA control group; however, no significant tumour shrinkage was observed. ConclusionEGFRvIII-targeting, glioblastoma cell-derived EVs can be used as siRNA delivery carriers for targeted gene therapy in glioblastoma. However, further optimization of siRNA delivery and treatment duration is required.

pharmacology and toxicology↗