Biology subjects

Araujo, J. P.

Publications and source records attributed to Araujo, J. P..

5 recordsLinked to original sources

bioRxiv2026

BDNF and glucocorticoids modulate neuroplasticity via direct interaction between TRKB and glucocorticoid receptors

The overlapping effects on neuronal plasticity of acute increase in glucocorticoid levels and the BDNF-TRKB signaling indicate a deep interconnection between the two pathways. Moreover, chronic stress with elevated glucocorticoids levels and downregulation of TRKB signaling associated with reduced BDNF are both involved in the pathophysiology of different psychiatric disorders. However, the mechanism by which TRKB and glucocorticoid receptors are recruited together in the modulation of neuronal plasticity is not clear yet. In this study we investigated the molecular mechanisms underlying the interplay of glucocorticoids and TRKB signaling in vitro and in vivo. We found that although not binding directly to TRKB, glucocorticoids promote TRKB dimerization and signaling similarly to BDNF. Moreover, the glucocorticoid receptor physically interacts with TRKB, modulating its dimerization and activity both in presence and in absence of glucocorticoids and contributing to TRKB-mediated plasticity. The transmembrane domain of TRKB is important for the interaction and for mediating the behavioral effects of TRKB and glucocorticoid receptor modulation, suggesting at least a partial overlap between the two signaling pathways. These results shed light on the interconnected effects of glucocorticoid and TRKB signaling highlighting the need for a more comprehensive understanding of the role and the dysfunction of different players contributing to synaptic plasticity.

neuroscience↗

bioRxiv2026

Fingolimod acutely facilitates the activation of TRKB

Fingolimod (FNG) is a sphingosine-1-phosphate receptor agonist currently prescribed for the treatment of remitting-relapsing multiple sclerosis. However, an increasing body of evidence indicates that FNG has a variety of other effects on the central nervous system, making it a good candidate to target other brain disorders that display loss of neuronal cells and synaptic plasticity. FNG treatments induce production of brain-derived neurotrophic factor (BDNF), which promotes neuronal plasticity, arborization and survival via signaling through its cognate receptor TRKB. In this study we characterize the relationship between FNG and TRKB in vitro and in vivo following acute treatments. We found that FNG induces TRKB activation in primary neuronal cultures in a BDNF-dependent way, indicating a rapid effect of FNG. This effect is different from the one elicited by antidepressants and is likely mediated by modulation of plasma membrane properties, as the enhancement of fluoxetine binding and dimerization of the cholesterol-insensitive TRKB mutant Y433F mimic the effects of cholesterol. Moreover, acute FNG treatment normalizes the generalization of conditioned fear response seen in heterozygous BDNF null female mice without affecting the wild-type littermates. Taken together, our data indicate that FNG allosterically promotes TRKB signaling and thereby induces the increase in BDNF production, which mediates the therapeutic effects of the drug on neuronal plasticity.

neuroscience↗

bioRxiv2025

Biological and genomic characterization of a new chlorovirus isolate expands the diversity and complexity of giant algal viruses in Brazil

A novel giant virus was isolated from a freshwater sample collected in Para de Minas city, Minas Gerais state, Brazil. The new isolate, named BR-AMG2, is a chlorovirus infecting the microalga Chlorella variabilis. Members of the family Phycodnaviridae, the chloroviruses have large linear dsDNA genomes (285-410 kbp), encoding hundreds of proteins and tRNAs. Despite their ecological and evolutionary importance, chloroviruses remain poorly studied, especially in South America. This study aimed to expand the understanding of this viral group by isolating and fully characterizing new chloroviruses in Brazil. After inoculating alga cultures with environmental samples, cytopathic effects, marked by lysis plaque formation, were observed 72 hours post-sampling. Chlorovirus BR-AMG2 remained stable across a temperature range of - 30 {degrees}C to 37 {degrees}C, yet was highly sensitive to UV exposure. This virus has a 160 nm icosahedral capsid and establishes a large viral factory in the host cytoplasm. Whole genome sequencing revealed a 338,043 bp genome, containing 11 tRNAs and 388 protein-coding sequences. We observed an extensive DNA methylation machinery, accounting for [~]5% of gene content in this isolate, suggesting a highly methylated genome. Phylogenetic reconstruction and Average Nucleotide Identity analyses confirmed that BR-AMG2 is a new member of the species Chlorovirus americanus, the first isolate recovered from a tropical region of the planet. Additionally, we observed a slight expansion of the species pangenome, suggesting ongoing genetic innovation with new isolates. Altogether, our results expand our knowledge about the viral diversity in Brazil and provide valuable insights into the biology of giant algae-infecting viruses.

microbiology↗

bioRxiv2022

Discovering genomic regions associated with the phenotypic differentiation of European local pig breeds

BackgroundIntensive selection of modern pig breeds resulted in genetic improvement of productive traits while local pig breeds remained less performant. As they have been bred in extensive systems, they have adapted to specifical environmental conditions resulting in a rich genotypic and phenotypic diversity. This study is based on European local pig breeds genetically characterized using DNA-pool sequencing data and phenotypically characterized using breed level phenotypes related to stature, fatness, growth and reproductive performance traits. These data were analyzed using a dedicated approach to detect selection signatures linked to phenotypic traits in order to uncover potential candidate genes that may be under adaptation to specific environments. ResultsGenetic data analysis of European pig breeds revealed four main axes of genetic variation represented by Iberian and modern breeds (i.e. Large White, Landrace, and Duroc). In addition, breeds clustered according to their geographical origin, for example French Gascon and Basque breeds, Italian Apulo Calabrese and Casertana breeds, Spanish Iberian and Portuguese Alentejano breeds. Principal component analysis of phenotypic data distinguished between larger and leaner breeds with better growth potential and reproductive performance on one hand and breeds that were smaller, fatter, and had low growth and reproductive efficiency on the other hand. Linking selection signatures with phenotype identified 16 significant genomic regions associated with stature, 24 with fatness, 2 with growth and 192 with reproduction. Among them, several regions contained candidate genes with possible biological effect on stature, fatness, growth and reproduction performance traits. For example, strong associations were found for stature in two regions containing the ANXA4 and ANTXR1 genes, for fatness containing the DNMT3A and POMC genes and for reproductive performance containing the HSD17B7 gene. ConclusionsThe present study on European local pig breeds used a dedicated approach for searching selection signatures supported by phenotypic data at the breed level to identify potential candidate genes that may have adapted to different living environments and production systems. Results can be useful to define conservation programs of local pig breeds.

genetics↗

bioRxiv2020

Prediction of SARS-CoV interaction with host proteins during lung aging reveals a potential role for TRIB3 in COVID-19.

COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 (TRIB3) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of TRIB3 in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease.

genetics↗