Biology subjects

Silva, A. R.

Publications and source records attributed to Silva, A. R..

4 recordsLinked to original sources

bioRxiv2025

Intestinal stem cell marker MEX3A regulates PPARγ expression with functional impact in colorectal carcinogenesis

RNA-binding proteins (RBPs) are major effectors of post-transcriptional regulation. Recently, we described the role of MEX3A in maintaining intestinal stem cell identity and epithelial renewal by repressing the PPAR{gamma} pathway. This work aimed to study MEX3A functional impact in colorectal cancer (CRC). MEX3A and PPAR{gamma} expression profiles were characterized in murine and human models. CRISPR/Cas9-mediated MEX3A knockout was performed in patient-derived CRC tumoroids (PDCTs) and MEX3A RNA targets identified through the HyperTRIBE technique. Apc+/fl;Mex3a+/- mice presented a significant reduction in tumor burden. Apc+/fl;Kras+/G12D;Mex3a+/-mice presented a reduced tumor area, while corresponding tumoroids exhibited reduced growth and enhanced differentiation potential mediated by PPAR{gamma} signalling. MEX3A overexpression (85% of human CRC cases) was inversely correlated with PPAR{gamma} downregulation (72% of cases). Accordingly, MEX3A-depleted PDCTs showed decreased LGR5 expression, accompanied by increased PPAR{gamma} expression and higher sensitivity to 5-Fluorouracil/Oxaliplatin (FOLFOX)-based chemotherapy. The HyperTRIBE results revealed a direct interaction between MEX3A and PPARG transcripts. STATEMENT OF SIGNIFICANCEThese results emphasize that MEX3A plays a crucial role in colorectal carcinogenesis, partially through regulation of the PPARG pathway, mediating tumour development and response to therapy, thus constituting a potential therapeutic target.

cancer biology↗

bioRxiv2024

PEX39 facilitates the peroxisomal import of PTS2 proteins

Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (peroxins/PEXs) cause devastating disease. PEX7 binds newly synthesized proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this import pathway remain enigmatic. Utilizing in vitro assays, yeast, and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates PTS2-protein import by binding PEX7 and stabilizing its interaction with PTS2 cargo. PEX39 and PEX13, a peroxisomal membrane translocon protein, both possess a KPWE motif necessary for PEX7 binding. Sequential binding of PEX7 to this motif in PEX39 and PEX13 provides a novel paradigm for how PTS2 cargo engage the translocation machinery. Collectively, our work uncovers an ancient and functionally important relationship among PEX39, PEX7, and PEX13, offering insights that will advance our understanding of peroxisomal biogenesis and disease.

cell biology↗

bioRxiv2021

Comparison of brain activity while tasting of passion fruit juice sweetened with caloric and non-caloric sweeteners

Sweetener type can influence sensory properties and consumers acceptance and preference for low-calorie products. An ideal sweetener does not exist, and each sweetener must be used in situations to which it is best suited. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. Despite the interest in artificial sweeteners, little is known about how artificial sweeteners are processed in the human brain. Here, we evaluated brain signals of 11 healthy subjects when they tasted passion fruit juice equivalently sweetened with sucrose (9.4 g/100 g), sucralose (0.01593 g/100 g), or aspartame (0.05477 g/100 g). Electroencephalograms were recorded for two sites in the gustatory cortex (i.e., C3 and C4). Data with artifacts were disregarded, and the artifact-free data were used to feed a CNN. Our results indicated that the brain responses distinguish juice sweetened with different sweeteners with an average accuracy of 0.823. Practical ApplicationsFinding sweeteners that best fit consumer preferences evolves understanding how the gustatory cortex processes sweeteners. Ideal equivalence will occur when the brain is no longer able to distinguish stimuli that are consciously perceived. This study presents a method of signal acquisition using a single channel and an open-source processing environment. This would allow, for example, to disregard the use of a commercial electroencephalograph and expand the studies in this area and offering to food industry additional tools in the development of products sweetened with non-caloric sweeteners.

bioengineering↗

bioRxiv2019

Habitat loss does not always entail negative genetic consequences

Although habitat loss has large, consistently negative effects on biodiversity, its genetic consequences are not yet fully understood. In this paper, we assess the genetic consequences of extreme habitat loss driven by mining in two endemic plants from Amazonian Savannas. Our analyses are the first to overcome major methodological limitations like the confounding effect of habitat fragmentation, historical processes underpinning genetic differentiation, time-lags between the onset of disturbances and genetic outcomes, and the need for large numbers of samples, genetic markers and replicated landscapes to ensure sufficient statistical power. We found that both species are remarkably resilient, as genetic diversity and gene flow patterns were unaffected by habitat loss. Our study unambiguously demonstrates that it is not possible to generalize about the genetic consequences of habitat loss, and imply that future conservation efforts need to consider species-specific genetic information.

ecology↗