Increasing evidence indicates that excessive iron in selective regions of the brain may be involved in the etiology of neurodegenerative disorders. Accordingly, increased levels of iron have been described in brain regions of patients in Parkinsons and Alzheimers diseases. We have characterized neonatal iron loading in rodents as a novel experimental model that mimics the brain iron accumulation observed in patients with neurodegenerative diseases and produces severe cognitive impairment in the adulthood. In the present study we have investigated the involvement of the cholinergic system on iron-induced memory impairment. The effects of a single administration of the acetylcholinesterase (AChE) inhibitor galantamine or the muscarinic receptor agonist oxotremorine on iron-induced memory deficits in rats were examined. Male Wistar rats received vehicle or iron (10.0 mg/kg) orally at postnatal days 12 to 14. At the age of 2-3 months, animals were trained in a novel object recognition task. Iron-treated rats showed long-term impairments in recognition memory. The impairing effect was reversed by systemic administration of galantamine (1 mg/kg) immediately after training. In addition, iron-treated rats that received oxotremorine (0.5 mg/kg) showed enhanced memory retention. Rats given iron showed a decreased AChE activity in the striatum when compared to controls. The results suggest that, at least in part, iron-induced cognitive deficits are related to a dysfunction of cholinergic neural transmission in the brain. These findings might have implications for the development of novel therapeutic strategies aimed at ameliorating cognitive decline associated with neurodegenerative disorders.

The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. The novel viral lineages P.1 (Variant of Concern Gamma) and P.2, respectively identified in the Brazilian states of Amazonas and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed the whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraíba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) in order to monitor the spread of SARS-CoV-2 lineages in Brazil in the first months of 2021. Here, we showed a widespread dispersal of P.1 and P.2 across Brazilian regions and, except for Amazonas, P.2 was the predominant lineage identified in the sampled states. We estimated the origin of P.2 lineage to have happened in February, 2020 and identified that it has differentiated into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December and its origin was inferred to have happened in August 2020. We also confirmed the presence of lineage P.7, recently described in the southernmost region of Brazil, to have spread across the Northeastern states. P.1, P.2 and P.7 are descended from the ancient B.1.1.28 strain, which co-dominated the first phase of the pandemic in Brazil with the B.1.1.33 strain. We also identified the occurrence of a new lineage descending from B.1.1.33 that convergently carries the E484K mutation, N.9. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to identify novel variants of interest and monitor for vaccine effectiveness.

The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. Novel SARS-CoV-2 lineages P.1 and P.2, first identified respectively in Manaus and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed a whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraíba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) aiming to identify SARS-CoV-2 mutations that could be involved in the surge of COVID19 cases in Brazil. Here, we showed a widespread dispersion of P.1 and P.2 across Brazilian regions. Except for Manaus, P.2 was the predominant lineage identified country-wise. P.2 lineage was estimated to have originated in February, 2020 and has diverged into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December. P.1 origin was inferred to have happened in August 2020. We also confirmed the presence of the variant under investigation (VUI) NP13L, recently described in the southernmost region of Brazil, to have spread across the Northeastern states. P.1, P.2 and NP13L are descended from the ancient B.1.1.28 strain, although during the first phase of the pandemic in Brazil presence of B.1.1.33 strain was also reported. We investigate here the possible occurrence of a new variant of interest descending from B.1.1.33 that also carries the E484K mutation. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to early identify novel variants of interest and to monitor for vaccine effectiveness.

Streptococcus agalactiae, known as group B streptococci (GBS), colonizes the digestive and genitourinary tracts and causes neonatal diseases and infections in immunocompromised and elderly individuals. GBS neonatal disease prevention includes intrapartum antibiotic prophylaxis. We characterized 101 GBS isolates obtained from patients in João Pessoa, northeastern Brazil, owing to the need to develop and implement vaccines to prevent GBS infections. Capsular types were determined using multiplex-PCR, and antibiotic susceptibility profiles were determined using disc diffusion or the gradient strip method. Clonal diversity was evaluated using pulsed-field gel electrophoresis. Fourteen selected isolates had the genome sequenced and evaluated for virulence and resistance genes. The GBS population had high clonal diversity, with serotype Ia and V prevalence. Among the sequenced isolates, we detected antibiotic resistance genes (ant(6)-Ia, catA8, ermA, ermB, lsaE, lsnuB, mefA/msrD, tetM, tetO, and tetS), several virulence genes, and mobile genetic elements integrated into the chromosome. The most frequent Sequence Type (ST) was ST144, followed by ST196, ST28, ST19, ST12, ST23, ST103, and the new ST1983 (CC103). Phylogenetically, ST103 and ST1983 were distant from the other STs. Our data revealed highly virulent GBS strains in this population and a new ST that could be related to a zoonotic origin.