VINICIUS DAGUANO GASTALDI
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- C-4 and crassulacean acid metabolism within a single leaf: deciphering key components behind a rare photosynthetic adaptation(2020) FERRARI, Renata C.; BITTENCOURT, Priscila P.; RODRIGUES, Maria A.; MORENO-VILLENA, Jose J.; ALVES, Frederico R. R.; GASTALDI, Vinicius D.; BOXALL, Susanna F.; DEVER, Louisa V.; DEMARCO, Diego; ANDRADE, Sonia C. S.; EDWARDS, Erika J.; HARTWELL, James; FRESCHI, LucianoAlthough biochemically related, C-4 and crassulacean acid metabolism (CAM) systems are expected to be incompatible. However, Portulaca species, including P. oleracea, operate C-4 and CAM within a single leaf, and the mechanisms behind this unique photosynthetic arrangement remain largely unknown. Here, we employed RNA-seq to identify candidate genes involved exclusively or shared by C-4 or CAM, and provided an in-depth characterization of their transcript abundance patterns during the drought-induced photosynthetic transitions in P. oleracea. Data revealed fewer candidate CAM-specific genes than those recruited to function in C-4. The putative CAM-specific genes were predominantly involved in night-time primary carboxylation reactions and malate movement across the tonoplast. Analysis of gene transcript-abundance regulation and photosynthetic physiology indicated that C-4 and CAM coexist within a single P. oleracea leaf under mild drought conditions. Developmental and environmental cues were shown to regulate CAM expression in stems, whereas the shift from C-4 to C-4-CAM hybrid photosynthesis in leaves was strictly under environmental control. Moreover, efficient starch turnover was identified as part of the metabolic adjustments required for CAM operation in both organs. These findings provide insights into C-4/CAM connectivity and compatibility, contributing to a deeper understanding of alternative ways to engineer CAM into C-4 crop species.
- Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity(2021) REIS, Viviane Neri de Souza; TAHIRA, Ana Carolina; GASTALDI, Vinicius Daguano; MARI, Paula; PORTOLESE, Joana; SANTOS, Ana Cecilia Feio dos; LISBOA, Bianca; MARI, Jair; CAETANO, Sheila C.; BRUNONI, Decio; BORDINI, Daniela; PAULA, Cristinane Silvestre de; VENCIO, Ricardo Z. N.; QUACKENBUSH, John; BRENTANI, HelenaAlthough Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR(2) = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.
- Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation(2021) OLIVEIRA, Katia Cristina de; CAMILO, Caroline; GASTALDI, Vinicius Daguano; FELTRIN, Arthur Sant'Anna; LISBOA, Bianca Cristina Garcia; PAULA, Vanessa de Jesus Rodrigues de; MORETTO, Ariane Cristine; LAFER, Beny; HOEXTER, Marcelo Queiroz; MIGUEL, Euripedes Constantino; MASCHIETTO, Mariana; BRENTANI, HelenaBackground Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. Results There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. Conclusions DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
- DNA methylation mediates a randomized controlled trial home-visiting intervention during pregnancy and the Bayley infant's cognitive scores at 12 months of age(2022) EUCLYDES, Veronica L. V.; GASTALDI, Vinicius D.; FELTRIN, Arthur S.; HOFFMAN, Daniel J.; GOUVEIA, Gisele; COGO, Hugo; FELIPE-SILVA, Aloisio; VIEIRA, Rossana P.; MIGUEL, Euripedes C.; V, Guilherme Polanczyk; CHIESA, Anna; FRACOLLI, Lislaine; MATIJASEVICH, Alicia; FERRARO, Alexandre; ARGEU, Adriana; MASCHIETTO, Mariana; BRENTANI, Helena P.The crosstalk between maternal stress exposure and fetal development may be mediated by epigenetic mechanisms, including DNA methylation (DNAm). To address this matter, we collect 32 cord blood samples from low-income Brazilian pregnant adolescents participants of a pilot randomized clinical intervention study (ClinicalTrials.gov, Identifier: NCT02807818). We hypothesized that the association between the intervention and infant neurodevelopmental outcomes at 12 months of age would be mediated by DNAm. First, we searched genome methylation differences between cases and controls using different approaches, as well as differences in age acceleration (AA), represented by the difference of methylation age and birth age. According to an adjusted p-value <= 0.05 we identified 3090 differentially methylated positions- CpG sites (DMPs), 21 differentially methylated regions (DMRs) and one comethylated module weakly preserved between groups. The intervention group presented a smaller AA compared to the control group (p = 0.025). A logistic regression controlled by sex and with gestational age indicated a coefficient of -0.35 towards intervention group (p = 0.016) considering AA. A higher cognitive domain score from Bayley III scale was observed in the intervention group at 12 months of age. Then, we performed a potential causal mediation analysis selecting only DMPs highly associated with the cognitive domain (adj. R (2) > 0.4), DMRs and CpGs of hub genes from the weakly preserved comethylated module and epigenetic clock as raw values. DMPs in STXBP6, and PF4 DMR, mediated the association between the maternal intervention and the cognitive domain at 12 months of age. In conclusion, DNAm in different sites and regions mediated the association between intervention and cognitive outcome.
- Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure(2022) EUCLYDES, Veronica; GOMES, Catarina; GOUVEIA, Gisele; GASTALDI, Vinicius Daguano; FELTRIN, Arthur Sant'Anna; CAMILO, Caroline; VIEIRA, Rossana Pulcineli; FELIPE-SILVA, Aloisio; GRISI, Sandra; FINK, Gunther; BRENTANI, Alexandra; BRENTANI, HelenaBackground Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. Results Using the Western Region Birth Cohort (ROC-Sao Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R-2 = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26-113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04-0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R-2 = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04-2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. Conclusion Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition.
- Putative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorders(2019) TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GASTALDI, Vinicius Daguano; TOLEDO, Victor Hugo Calegari de; PEREIRA, Jose Geraldo de Carvalho; LISBOA, Bianca Cristina Garcia; REIS, Viviane Neri de Souza; SANTOS, Ana Cecilia Feio dos; MASCHIETTO, Mariana; BRENTANI, HelenaThe male-biased prevalence of certain neurodevelopmental disorders and the sex-biased outcomes associated with stress exposure during gestation have been previously described. Here, we hypothesized that genes distinctively targeted by only one or both homologous proteins highly conserved across therian mammals, SOX3 and SRY, could induce sexual adaptive changes that result in a differential risk for neurodevelopmental disorders. ChIP-seq/chip data showed that SOX3/SRY gene targets were expressed in different brain cell types in mice. We used orthologous human genes in rodent genomes to extend the number of SOX3/SRY set (1,721). These genes were later found to be enriched in five modules of coexpressed genes during the early and mid-gestation periods (FDR < 0.05), independent of sexual hormones. Genes with differential expression (24, p < 0.0001) and methylation (40, p < 0.047) between sexes were overrepresented in this set. Exclusive SOX3 or SRY target genes were more associated with the late gestational and postnatal periods. Using autism as a model sex-biased disorder, the SOX3/SRY set was enriched in autism gene databases (FDR <= 0.05), and there were more de novo variations from the male autism spectrum disorder (ASD) samples under the SRY peaks compared to the random peaks (p < 0.024). The comparison of coexpressed networks of SOX3/SRY target genes between male autism and control samples revealed low preservation in gene modules related to stress response (99 genes) and neurogenesis (78 genes). This study provides evidence that while SOX3 is a regulatory mechanism for both sexes, the male-exclusive SRY also plays a role in gene regulation, suggesting a potential mechanism for sex bias in ASD.