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- Abnormal habituation of the auditory event-related potential P2 component in patients with schizophreniaPublication . Mazer, Prune; Macedo, Inês; Paiva, Tiago O.; Ferreira-Santos, Fernando; Paison, Rita; Barbosa, Fernando; Almeida, Pedro; Silveira, Celeste; Cunha-Reis, Cassilda; Marques-Teixeira, JoãoAuditory event-related potentials (ERP) may serve as diagnostic tools for schizophrenia and inform on the susceptibility for this condition.Particularly, the examination of N1 and P2 components of the auditory ERP may shed light on the impairments of information processing streams in schizophrenia. However, the habituation properties (i.e., decreasing amplitude with the repeated presentation of an auditory stimulus) of these components remain poorly studied compared to other auditory ERPs.
- Adaptive model for biofeedback data flows management in the design of interactive immersive environmentsPublication . Gomes, Paulo Veloso; Marques, António; Donga, João; Sá, Catarina; Correia, António; Pereira, JavierThe interactivity of an immersive environment comes up from the relationship that is established between the user and the system. This relationship results in a set of data exchanges between human and technological actors. The real-time biofeedback devices allow to collect in real time the biodata generated by the user during the exhibition. The analysis, processing and conversion of these biodata into multimodal data allows to relate the stimuli with the emotions they trigger. This work describes an adaptive model for biofeedback data flows management used in the design of interactive immersive systems. The use of an affective algorithm allows to identify the types of emotions felt by the user and the respective intensities. The mapping between stimuli and emotions creates a set of biodata that can be used as elements of interaction that will readjust the stimuli generated by the system. The real-time interaction generated by the evolution of the user’s emotional state and the stimuli generated by the system allows him to adapt attitudes and behaviors to the situations he faces.
- Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cellsPublication . Pinho dos Santos Graça, Maria Inês; Sousa, Elsa Joana; Baptista, Tiago; Almeida, Mafalda; Ramalho-Carvalho, João; Palmeira, Carlos; Henrique, Rui; Jerónimo, CarmenCurrent therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines. The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively. Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA re-expression was only attained GSTP1 and APC. RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.
- Antimicrobial and cytotoxic assessment of marine cyanobacteria - synechocystis and synechococcusPublication . Martins, Rosario; Ramos, Miguel; Herfindal, Lars; Sousa, José; Skærven, Kaja; Vasconcelos, VítorAqueous extracts and organic solvent extracts of isolated marine cyanobacteria strains were tested for antimicrobial activity against a fungus, Gram-positive and Gram-negative bacteria and for cytotoxic activity against primary rat hepatocytes and HL-60 cells. Antimicrobial activity was based on the agar diffusion assay. Cytotoxic activity was measured by apoptotic cell death scored by cell surface evaluation and nuclear morphology. A high percentage of apoptotic cells were observed for HL-60 cells when treated with cyanobacterial organic extracts. Slight apoptotic effects were observed in primary rat hepatocytes when exposed to aqueous cyanobacterial extracts. Nine cyanobacteria strains were found to have antibiotic activity against two Gram-positive bacteria, Clavibacter michiganensis subsp. insidiosum and Cellulomonas uda. No inhibitory effects were found against the fungus Candida albicans and Gram-negative bacteria. Marine Synechocystis and Synechococcus extracts induce apoptosis in eukaryotic cells and cause inhibition of Gram-positive bacteria. The different activity in different extracts suggests different compounds with different polarities.
- Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strainsPublication . Leão, Pedro N.; Costa, Margarida; Ramos, Vitor; Pereira, Alban R.; Fernandes, Virgínia C.; Domingues, Valentina F.; Gerwick, William H.; Vasconcelos, Vítor; Martins, RosárioCyanobacteria are widely recognized as a valuable source of bioactive metabolites. The majority of such compounds have been isolated from so-called complex cyanobacteria, such as filamentous or colonial forms, which usually display a larger number of biosynthetic gene clusters in their genomes, when compared to free-living unicellular forms. Nevertheless, picocyanobacteria are also known to have potential to produce bioactive natural products. Here, we report the isolation of hierridin B from the marine picocyanobacterium Cyanobium sp. LEGE 06113. This compound had previously been isolated from the filamentous epiphytic cyanobacterium Phormidium ectocarpi SAG 60.90, and had been shown to possess antiplasmodial activity. A phylogenetic analysis of the 16S rRNA gene from both strains confirmed that these cyanobacteria derive from different evolutionary lineages. We further investigated the biological activity of hierridin B, and tested its cytotoxicity towards a panel of human cancer cell lines; it showed selective cytotoxicity towards HT-29 colon adenocarcinoma cells.
- Are known cyanotoxins involved in the toxicity of picoplanktonic and filamentous north atlantic marine cyanobacteria?Publication . Frazão, Bárbara; Martins, Rosario; Vasconcelos, VítorEight marine cyanobacteria strains of the genera Cyanobium, Leptolyngbya, Oscillatoria, Phormidium, and Synechococcus were isolated from rocky beaches along the Atlantic Portuguese central coast and tested for ecotoxicity. Strains were identified by morphological characteristics and by the amplification and sequentiation of the 16S rDNA. Bioactivity of dichloromethane, methanol and aqueous extracts was assessed by the Artemia salina bioassay. Peptide toxin production was screened by matrix assisted laser desorption/ionization time of flight mass spectrometry. Molecular analysis of the genes involved in the production of known cyanotoxins such as microcystins, nodularins and cylindrospermopsin was also performed. Strains were toxic to the brine shrimp A. salina nauplii with aqueous extracts being more toxic than the organic ones. Although mass spectrometry analysis did not reveal the production of microcystins or other known toxic peptides, a positive result for the presence of mcyE gene was found in one Leptolyngbya strain and one Oscillatoria strain. The extensive brine shrimp mortality points to the involvement of other unknown toxins, and the presence of a fragment of genes involved in the cyanotoxin production highlight the potential risk of cyanobacteria occurrence on the Atlantic coast.
- Autistic traits and event-related potentials in the general population: A scoping review and meta-analysisPublication . Mazer, Prune; Garcez, Helena; Macedo, Inês; Pasion, Rita; Silveira, Celeste; Sempf, Frederieke; Ferreira-Santos, FernandoDifferences in short and long-latency Event-Related Potentials (ERPs) can help us infer abnormalities in brain processing, considering early and later stages of stimuli processing across tasks and conditions. In autism research, the adult population remains largely understudied compared to samples at early stages of development. In this context, this scoping review briefly summarises what has been described in community and subclinical adult samples of autism. The current scoping review and meta-analysis includes 50 records (N = 1652) and comprehensively explores short and long-latency ERP amplitudes and their relationship with autistic traits in adult community samples. This meta-analysis identified, with small to medium effect sizes, distinctive patterns in late ERP amplitudes, indicating enhanced responses to visual stimuli and the opposite patterns to auditory tasks in the included sample. Additionally, a pattern of higher amplitudes was also found for the component P3b in autistic traits. Differential effects in visual and auditory domains are explored in light of the predictive processing framework for Autism. It remains possible that different brain mechanisms operate to explain symptoms related with different sensory modalities. P3b is discussed as a possible component of interest in future studies as it revealed a more robust effect for differentiating severity in the expression of autistic traits in adulthood
- Behavior of prostate cancer cells in a nanohydroxyapatite/collagen bone scaffoldPublication . Cruz-Neves, Susana; Ribeiro, Nilza; Pinho dos Santos Graça, Maria Inês; Jerónimo, Carmen; Sousa, Susana R.; Monteiro, Fernando J.Prostate cancer (PCa) is the second leading cause of death among men in Europe and U.S. The metastatic dissemination pattern of PCa is unique, developing bone metastasis as the only site of progression, consequently with a prognosis very poor. The cancer cells interactions within the surrounding bone environment are critical for tumor growth and progression. Secreted protein, acidic and rich in cysteine (SPARC) is described to be involved in PCa cells migration and invasion into bone. Three-dimensional (3D) in vitro systems that are able to closely resemble the in vivo microenvironment are recently taking importance in cancer research. Original nanohydroxyapatite/collagen scaffolds were designed to resemble bone microenvironment in order to be applied as substitutes in bone defects and as potential biomaterials to mimic skeletal tumors. In fact, these 3D structures were cytocompatible and able to support osteoblast (MC3T3-E1) colonization and to promote bone ingrowth. Additionally, SPARC adsorption onto the scaffolds affected PC3 and LNCaP PCa cell lines behavior. PC3 cells were found to adapt and colonize the scaffolds, differing from LNCaP where cells underwent morphogenic changes and grew as clusters. Furthermore, for the tested SPARC concentration, SPARC plays a role in retaining LNCaP cells at the latter time points while with PC3 cells no significant differences were observed. This characterization study is required to establish a bone model to provide new insights into the poorly understood PCa mechanisms of metastasis to bone and the generation of improved therapies.
- Biosynthesis-assisted structural elucidation of the bartolosides, chlorinated aromatic glycolipids from cyanobacteriaPublication . Leão, Pedro N.; Nakamura, Hitomi; Costa, Margarida; Pereira, Alban R.; Martins, Rosario; Vasconcelos, Vítor; Gerwick, William H.; Balskus, Emily P.The isolation of the bartolosides, unprecedented cyanobacterial glycolipids featuring aliphatic chains with chlorine substituents and C-glycosyl moieties, is reported. Their chlorinated dialkylresorcinol (DAR) core presented a major structural-elucidation challenge. To overcome this, we discovered the bartoloside (brt) biosynthetic gene cluster and linked it to the natural products through in vitro characterization of the DAR-forming ketosynthase and aromatase. Bioinformatic analysis also revealed a novel potential halogenase. Knowledge of the bartoloside biosynthesis constrained the DAR core structure by defining key pathway intermediates, ultimately allowing us to determine the full structures of the bartolosides. This work illustrates the power of genomics to enable the use of biosynthetic information for structure elucidation.
- Bridging cyanobacteria to neurodegenerative diseases: a new potential source of bioactive compounds against Alzheimer’s diseasePublication . Castaneda, Andrea; Ferraz, Ricardo; Vieira, Mónica; Cardoso, Isabel; Vasconcelos, Vítor; Martins, RosárioNeurodegenerative diseases (NDs) represent a drawback in society given the ageing population. Dementias are the most prevalent NDs, with Alzheimer’s disease (AD) representing around 70% of all cases. The current pharmaceuticals for AD are symptomatic and with no effects on the progression of the disease. Thus, research on molecules with therapeutic relevance has become a major focus for the scientific community. Cyanobacteria are a group of photosynthetic prokaryotes rich in biomolecules with confirmed activity in pathologies such as cancer, and with feasible potential in NDs such as AD. In this review, we aimed to compile the research works focused in the anti-AD potential of cyanobacteria, namely regarding the inhibition of the enzyme β-secretase (BACE1) as a fundamental enzyme in the generation of β-amyloid (Aβ), the inhibition of the enzyme acetylcholinesterase (AChE) lead to an increase in the availability of the neurotransmitter acetylcholine in the synaptic cleft and the antioxidant and anti-inflammatory effects, as phenomena associated with neurodegeneration mechanisms.