Percorrer por autor "Cavadas, Bruno"
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- CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extensionPublication . Celestino, Ricardo; Nome, Torfinn; Pestana, Ana; Hoff, Andreas M.; Gonçalves, A. Pedro; Pereira, Luísa; Cavadas, Bruno; Eloy, Catarina; Bjøro, Trine; Sobrinho-Simões, Manuel; Skotheim, Rolf I.; Soares, PaulaBackground: The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis. Methods: We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers. Results: We identified 17 genes significantly differentially expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be independent predictors of extrathyroidal extension in DTC. Conclusions: We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 maybe useful for prognostic purposes.
- Intersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampusPublication . Terceiro, Ana Filipa; Lobo, Andrea; Socodato, Renato; Canedo, Teresa; Silva, Ana Isabel; Cavadas, Bruno; Carvalhais, Lia G.; Aroso, Miguel; Morello, Gabriela M.; Aguiar, Paulo; Magalhães, Ana; Carvalho, Ana Luísa; Relvas, João B.; Fonseca, Rosalina; Summavielle, Teresa; Summavielle, TeresaThe development and maintenance of drug addiction triggered by psychoactive substances, such as methamphetamine (Meth), is strongly influenced by synaptic and morphological adaptations in the brain. The hippocampus has a key role in the formation of maladaptive drug-context associations and relapse. However, the mechanisms regulating this complex process are not completely understood. Recent studies highlight that the actin cytoskeleton and its regulatory proteins play a fundamental role in morphological and behavioral plasticity associated with drug use. Here, we show that a binge pattern of Meth administration is sufficient to increase hippocampal neurite outgrowth and dendritic spine density leading to augmented basal synaptic transmission and impaired long-term potentiation (LTP) response. To study the molecular pathways affected by Meth, we used embryonic primary neuron cultures from the hippocampus and performed RNA Sequencing from isolated soma or neurites compartments, FRET microscopy, biochemical analyses, and morphometric measurements of dendrites to demonstrate that intersectin (Itsn)1/cdc42 signaling is an important mediator of Meth-induced morphological adaptations, specifically in the synaptic compartment. Furthermore, AAV-mediated depletion of neuronal cdc42 in the hippocampus prevented Meth-induced changes in cytoarchitecture and their consequent impact on neuronal functionality. Our results highlight relevant compartment-associated changes in the activity of Itsn1/cdc42 pathway that critically regulate Meth-induced neuronal remodeling and plasticity.
- Meningeal γδ T cells facilitate bacterial entry into the brain in neonatal meningitis and trigger long-term behavioural sequelaePublication . Lorga, Inês; Soares, Joana; Bravo, Joana; Mesquita, Pedro; Ribeiro, Nuno; Rodrigues, João; Hassan, Ahmed; Mesquita, Morgana; Cavadas, Bruno; Georgiev, Hristo; Magalhães, Ana; Summavielle, Teresa; Vilanova, Manuel; Ribot, Julie C.; Andrade, Elva Bonifácio; Bonifácio Andrade, Elva; Summavielle, TeresaNeonatal bacterial meningitis is a life-threatening condition and a leading cause of neurodevelopmental impairment among survivors. Despite its prevalence, the role of meningeal immunity on disease pathology during early life remains largely unexplored. Using a clinically relevant mouse model of neonatal group B streptococcal meningitis and single-cell RNA sequencing, we observed that IL-17A (IL-17)-producing γδ T cells (γδ17 T cells) accumulate in the meninges during the acute phase of infection and persist throughout the lifespan. Importantly, mice deficient in γδ T cells or in IL-17 show a significantly lower bacterial colonisation in the brain parenchyma, and IL-17 neutralisation in the cerebrospinal fluid leads to a similar phenotype. Reduced blood-brain barrier permeability in the absence of γδ T cells results in decreased bacterial invasion and diminished microglia activation. Wild-type but not γδ T cell-deficient mice surviving infection exhibit increased hyperactivity and open space anxiety during early adulthood, a behavioural profile that may reflect attention deficit and hyperactivity (ADHD)-like tendencies. Altogether, these findings establish a pathogenic role for meningeal γδ17 T cells in early life, uncovering a key mechanism that drives long-term sequelae in GBS neonatal meningitis.