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Barbosa, L. S.

Publications and source records attributed to Barbosa, L. S..

5 recordsLinked to original sources

Dynamics of dopamine transients in human olfactory epithelium during reward learning

Dopamine signaling is crucial for motivation, movement, and learning, but has remained beyond the reach of measurement in healthy humans. Here, we measured sub-second dopamine in the olfactory epithelium of healthy humans during two reward learning tasks with distinct reward types: liquid reward during a conditioning task and monetary reward during an economic exchange game. In both tasks, as trials progress, peak dopamine transients shift from rewarding outcomes back to reward-predictive cues. In the economic game, this pattern retrains quickly when reward magnitude or reward timing is changed without warning. These findings match the time transfer characteristics and amplitude dependence of temporal difference prediction error signals. The results also establish a new, minimally invasive route for recording fast dopamine signaling in healthy humans: the nose.

neuroscience↗

Dopamine dynamics in human anterior cingulate cortex during Pavlovian-instrumental conflict

Dopamine is believed to modulate not only instrumental learning about the link between states, actions, and outcomes but also reflexive behaviours, such as a Pavlovian bias to approach in rewarding states and freeze in aversive ones. We studied these dual roles in the human brain, by combining intracranial dopamine recordings from the anterior cingulate cortex (ACC)-- a region implicated in behavioural and cognitive control -- with a motivational Go/NoGo task involving conflict between instrumental and Pavlovian action selection. We found evidence that dopamine in the ACC is involved in evaluating whether Pavlovian responding should guide behaviour. This computational motif was observed across multiple task events, including in response to rewards and punishments, and in analyses based on a reinforcement learning model. Our results indicate that dopamine supports learning at the more abstract level of behavioural policies in addition to the more concrete levels of states and actions.

neuroscience↗

Dopamine and serotonin transients predict depressive symptom relief following deep brain stimulation of human subcallosal cingulate cortex

Recent advances in deep brain stimulation (DBS) of the subcallosal cingulate (SCC) show promise in mitigating the symptoms of treatment-resistant depression (TRD) in humans1-3. Monoamines, such as dopamine and serotonin, mediate the effects of pharmacological treatments of depression. However, their roles in recovery following DBS remain elusive, largely due to technical limitations of measuring these neurotransmitters in the living human brain. Here, by leveraging machine learning-enhanced electrochemistry4-7, we show that dopamine and serotonin signaling following DBS to the SCC predicted later depressive symptom relief in humans with TRD. We found that both dopamine and serotonin levels increased following subtherapeutic intraoperative SCC stimulation, with each neurotransmitter showing selective responses to distinct decision-making tasks. Furthermore, acute dopamine increases predicted later mood improvements during a social decision-making task, while serotonin enhancement predicted faster responses during a non-social learning task longitudinally. Critically, changes in dopamine and serotonin levels during the social decision-making task jointly predicted depressive symptom remission at 6-month follow-up. These findings illustrate the contribution of both dopamine and serotonin signaling in predicting behavioral improvement and depressive symptom remission in humans with TRD. Such neurochemical plasticity may serve as potential mechanistic biomarkers for SCC DBS mechanism and TRD treatment response. Significance statementO_LIDopamine and serotonin levels increased following acute DBS to the SCC in humans. C_LIO_LIAcute dopamine and serotonin changes predicted later mood and response speed changes. C_LIO_LISustained TRD recovery was predicted by acute increases in both dopamine and serotonin estimates. C_LI

neuroscience↗

The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies

Antimicrobial resistance is an increasing worldwide public health burden that threatens to make the existent antimicrobials obsolete. Among the mechanisms of antimicrobial resistance is the overexpression of efflux pumps, such as the AcrA-AcrB-TolC which extrude diverse compounds, reducing the intracellular concentration of antimicrobials. TolC is the outer membrane protein of this pump and has recently gained attention as a therapeutic target. However, little is known about the immune response generated against the TolC protein. Here we evaluated the cellular and humoral immune response against the TolC from Escherichia coli. An in silico epitope prediction of the E. coli TolC showed several residues could bind to human antibodies, and we showed that human plasma presented anti-TolC IgG and IgA antibodies. Gram-negative infected patients presented a slight increase in anti-TolC IgM amounts, compared to controls. Recombinant E. coli TolC protein stimulated macrophages in vitro to produce nitric oxide, as well as IL-6 and TNF-, assessed by Griess assay and ELISA, respectively. Immunization of mice with TolC intraperitoneally and an in vitro re-stimulation of lymph node cells led to increased percentage of T cell proliferation and IFN{gamma} production, evaluated by flow cytometry and ELISA, respectively. We observed that TolC mouse immunization stimulated anti-TolC IgM and IgG production, with a higher level of IgG1 and IgG2, amongst the IgG subclasses. Finally, TolC IgG from mouse immune serum could bind to live E. coli, increase bacterial uptake by macrophages in vitro. TolC immunized mice had a survival rate increased in 60% post infection with E. coli. Our results showed that TolC is immunogenic, activating macrophages, T and B cells, leading to the production of protective antibodies against E. coli.

immunology↗

First report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil

BackgroundChikungunya virus (CHIKV) is an arbovirus that causes an acute febrile illness characterized by severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro.\n\nMethodsThe cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed.\n\nResultsThe results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples.\n\nConclusionsPhylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported.

microbiology↗