Browsing by Issue Date, starting with "2021-09-23"
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- Titanium Dioxide Nanoparticles molecular effects: Internalization in the Human Intestinal EpitheliumPublication . Rolo, Dora; Pereira, Joana FS; Matos, Paulo; Gonçalves, Lídia; Bettencourt, Ana Francisca; Jordan, Peter; Silva, Maria João; Louro, HenriquetaThe use of titanium dioxide nanoparticles (TiO2-NPs) as food additive and in food packaging demands a thorough assessment of their potential risk for human health, specifically with regard to gastrointestinal tract. Using intestinal cells, we analyzed the mechanisms by which digested TiO2-NPs (NM-102, NM-103 and NM-105, JRC repository) translocate through the intestinal epithelium layer, as compared to non-digested particles. Human digestion of TiO2-NPs was simulated using the INFOGEST in vitro harmonized digestion method. Caco-2 cells were grown as polarized cell monolayer for exposure and differentiation was evaluated by TEER. The translocation of TiO2-NPs, tagged with alizarin red, through the cell barrier was analysed by confocal microscopy, using colocalization with antibodies against specific endosomal compartments. The internalization of the TiO2-NPs was confirmed for the three TiO2-NPs tested, both before and after digestion simulation. The smallest TiO2-NPs were internalized into EEA1-positive early- endosomes and accumulated in late endosomes (Rab7), with only a small fraction following the degradative pathway to the lysosome (LAMP1). The data suggested that at least part of the TiO2-NPs could be redirected to the secretory pathway. Consistently, fluorescence passing from the apical to the basolateral chamber was observed, without disruption of the intestinal barrier function. The changes in cell function or signal transduction pathways are being studied and possible consequences to human gastrointestinal tract arediscussed. We thank the support from P. Alvito, C. Martins and R. Assunção (INSA,Lisbon, Portugal).
- Single Nucleotide Variant (SNV) analysis in Autism Spectrum DisorderPublication . Vilela, JoanaAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by communication deficits and repetitive behavioral patterns of variable degrees of clinical severity, and an important genetic component. There is strong evidence indicating that neurotransmission and synaptic processes are altered in ASD. Our objective was to identify ultra-rare variants in neurotransmission and synaptic (NS) genes that play a role in ASD, linking mutations to the biological pathways affected. We identified 357 variants in 208 genes in the ASD dataset, defining 7 network communities: Cytochrome P450 metabolism; Ion channel activity; Chemical synapse transmission; Neuronal development; G protein-coupled receptors; Energy metabolism and Neurotransmitter release cycle. The neuronal development community (27,6% of network cases; 54 genes), the Cytochrome P450 metabolism community (18,8% of network cases; 33 genes) and the G protein-coupled receptors community (16,1% of network cases; 32 genes), are the biological communities with the highest number of cases affected by ultra-rare SNVs in the network analysed. The majority of the network cases analyzed has mutations in genes involved in neuronal development, supporting the relevance of this pathway in ASD. This study reinforces the synaptic and neurotransmitter pathway hypothesis as one of the disease-relevant genetic drivers for ASD.
- Mycotoxins under the human biomonitoring initiative (HBM4EU)Publication . Alvito, Paula; Viegas, Susana; Silva, Maria JoãoAbout mycotoxins under the human biomonitoring initiative (HBM4EU).