Biology subjects

Nascimento, A.

Publications and source records attributed to Nascimento, A..

3 recordsLinked to original sources

bioRxiv2023

Decoding Duchenne muscular dystrophy transcriptome to single nuclei level reveals clinical-genetic correlations

The cellular and molecular consequences of lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression Duchenne and Becker muscular dystrophies. We analyzed muscle biopsies of DMD patients and controls using single nuclei RNA sequencing (snRNAseq) and correlated the results with clinical data. DMD samples displayed an increase in regenerative fibers, satellite cells and fibro-adipogenic progenitor cells (FAPs) and a decrease in slow fibers and smooth muscle cells. Samples from patients with stable mild weakness were characterized by an increase in regenerative fibers, while those from patients with progressive weakness had fewer muscle fibers and increased FAPs. DMD muscle fibers displayed a strong regenerative signature, while DMD FAPs upregulated genes producing extracellular matrix and molecules involved in several signaling pathways. An analysis of intercellular communication profile identified FAPs as a key regulator of cell signaling in DMD samples. We show significant differences in the gene expression profiled of the different cell populations present in DMD muscle samples compared to controls.

bioinformatics↗

bioRxiv2021

Comparison of bacterial communities from the surface and adjacent bottom layers water of Billings reservoir

Here, we describe the microbial diversity and physicochemical properties in freshwater samples from the surface and bottom layer of Billings reservoir in Sao Paulo state, Brazil. Twenty-two matched samples were characterized using the 16S rRNA gene Illumina MiSeq platform. Taxonomical composition revealed an abundance of Cyanobacteria phyla, followed by Proteobacteria, with 1903 and 2689 known bacterial genera in the surface and deep-water layers, respectively. Shannon diversity index ranging from 2.3 - 5.39 and 4.04 - 6.86 in the surface and bottom layer, respectively. Among the 120 pathogenic genera identified, Flavobacterium was the most predominant genus. Temperature and phosphorus concentration were the most influential factors in shaping the microbial communities of both layers. Predictive functional analysis suggests that the reservoir is enriched in motility genes involved in the flagellar assembly. The overall results present new information on the significantly altered diversity composition of the bacterial community detected in Billings freshwater reservoir. IMPORTANCEIn this study, we investigated the bacterial distribution, community composition, potential metabolic activity, potentially pathogenic bacteria, and toxin genes of Cyanobacteria in the bottom layers and surface along Billings reservoir in the southeast of Brazi. Our results provide essential information about the pattern of bacterioplankton communities variation inhabiting the Billings reservoir and the combination of environmental that shaped their structure. These results may help pave the way for future studies devoted to control and improve the water quality in the Billings reservoir, which is facing rapid urban development and urbanization.

microbiology↗

bioRxiv2020

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral main protease is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. Although several mechanisms of self-cleavage had been proposed for SARS-CoV, the lack of structural information for each step is a setback to the understanding of this process. Herein, we used X-ray crystallography to characterize an immature form of the main protease, which revealed major conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis-cleavage of N-terminal residues within the dimer, leading to the mature active site. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the main protease bound to its endogenous N and C-terminal residues during the formation of the tetramer. This quaternary form is also present in solution, suggesting a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during maturation, which can guide the development of new inhibitors targeting its intermediary states.

biochemistry↗