Biology subjects

Simoes, F.

Publications and source records attributed to Simoes, F..

4 recordsLinked to original sources

bioRxiv2025

Advances on the bacterial diversity and functionality of Platypus cylindrus - Quercus suber interaction

The ambrosia beetle Platypus cylindrus Fab. (Coleoptera: Curculionidae: Platypodinae) has been associated in Portugal with cork oak (Quercus suber) tree death since the 1980s. Although traditionally known as a secondary pest damaging stressed and dead trees, its aggressiveness changed over the last decades. Ambrosia beetle is an insect known for its interactions with several species of fungi aiming for the gain of biologic functions that facilitates its life cycle. How bacterial communities harbored by ambrosia beetle impact forest ecosystems is not yet well known. In oak species, some pathogenic bacteria are often associated with wood insect infestations. From P. cylindrus body and wood tree bored galleries, culture dependent methods led to the isolation of bacteria involved in wood degradation and beetle ecology and even a new bacterial cork oak pathogen. To complement colony isolation efforts for the identification of the beetle-cork oak associated bacterial community, the same samples were analyzed with 16S metabarcoding. Two distinct bacterial communities from beetle mycangia and wood galleries sharing the most abundant bacterial taxa were revealed. A group of genera from Enterobacterales and Bradyrhizobium prevailed in the samples from wood galleries. Comparison between ASVs and full 16S sequences allowed the identification of Pectobacteriaceae as the major taxon from unclassified Enterobacterales carried by the beetle. Prediction of metabolic pathways varying between wood galleries and beetle mycangia revealed upregulation in the galleries of carbohydrate and virulence factors. Together, these analyses efficiently compared the bacteriome from the wood galleries with the beetle mycangia, revealing different bacterial communities and specific ecological roles related to both the beetle and trees. Additionally, they gave insights into the comparability of culture-dependent and independent methods in bacteriome analysis.

ecology↗

bioRxiv2024

Systems biology-enabled targeting of NF-κB and BCL2 overcomes microenvironment-mediated BH3-mimetic resistance in DLBCL.

In Diffuse Large B-cell Lymphoma (DLBCL), elevated anti-apoptotic BCL2-family proteins (e.g., MCL1, BCL2, BCLXL) and NF-{kappa}B subunits (RelA, RelB, cRel) confer poor prognosis. Heterogeneous expression, regulatory complexity, and redundancy offsetting the inhibition of individual proteins, complicate the assignment of targeted therapy. We combined flow cytometry fingerprinting, immunofluorescence imaging, and computational modeling to identify therapeutic vulnerabilities in DLBCL. The combined workflow predicted selective responses to BCL2 inhibition (venetoclax) and non-canonical NF-{kappa}B inhibition (Amgen16). Within the U2932 cell line we identified distinct resistance mechanisms to BCL2 inhibition in cellular sub-populations recapitulating intratumoral heterogeneity. Co-cultures with CD40L-expressing stromal cells, mimicking the tumor microenvironment (TME), induced resistance to BCL2 and BCLXL targeting BH3-mimetics via cell-type specific upregulation of BCLXL or MCL1. Computational models, validated experimentally, showed that basal NF-{kappa}B activation determined whether CD40 activation drove BH3-mimetic resistance through upregulation of RelB and BCLXL, or cRel and MCL1. High basal NF-{kappa}B activity could be overcome by inhibiting BTK to resensitize cells to BH3-mimetics in CD40L co-culture. Importantly, non-canonical NF-{kappa}B inhibition overcame heterogeneous compensatory BCL2 upregulation, restoring sensitivity to both BCL2- and BCLXL-targeting BH3-mimetics. Combined molecular fingerprinting and computational modelling provides a strategy for the precision use of BH3-mimetics and NF-{kappa}B inhibitors in DLBCL.

cancer biology↗

bioRxiv2023

Metabolic specialization drives reduced pathogenicity in Pseudomonas aeruginosa CF clinical isolates

Metabolism provides the foundation for all cellular functions. During persistent infections, in adapted pathogenic bacteria metabolism functions radically differently compared with more naive strains. Whether this is simply a necessary accommodation to the persistence phenotype or if metabolism plays a direct role in achieving persistence in the host is still unclear. Here, we characterize a convergent shift in metabolic function(s) linked with the persistence phenotype during Pseudomonas aeruginosa colonization in the airways of people with cystic fibrosis. We show that clinically-relevant mutations in the key metabolic enzyme, pyruvate dehydrogenase, lead to a host-specialized metabolism together with a lower virulence and immune response recruitment. These changes in infection phenotype are mediated by impaired type III secretion system activity and by secretion of the antioxidant metabolite, pyruvate, respectively. Our results show how metabolic adaptations directly impinge on persistence and pathogenicity in this organism.

microbiology↗

bioRxiv2021

Downregulation of WT1 transcription factor gene expression is required to promote myocardial fate

During cardiac development, cells from the precardiac mesoderm fuse to form the primordial heart tube, which then grows by addition of further progenitors to the venous and arterial poles. In the zebrafish, wilms tumor 1 transcription factor a (wt1a) and b (wt1b) are expressed in the pericardial mesoderm at the venous pole of the forming heart tube. The pericardial mesoderm forms a single layered mesothelial sheet that contributes to further the growth of the myocardium, and forms the proepicardium. Proepicardial cells are subsequently transferred to the myocardial surface and give rise to the epicardium, the outer layer covering the myocardium in the adult heart. wt1a/b expression is downregulated during the transition from pericardium to myocardium, but remains high in proepicardial cells. Here we show that sustained wt1 expression impaired cardiomyocyte maturation including sarcomere assembly, ultimately affecting heart morphology and cardiac function. ATAC-seq data analysis of cardiomyocytes overexpressing wt1 revealed that chromatin regions associated with myocardial differentiation genes remain closed upon wt1b overexpression in cardiomyocytes, suggesting that wt1 represses a myocardial differentiation program. Indeed, a subset of wt1a/b-expressing cardiomyocytes changed their cell adhesion properties, delaminated from the myocardial epithelium, and upregulated the expression of epicardial genes, as confirmed by in vivo imaging. Thus, we conclude that wt1 acts as a break for cardiomyocyte differentiation by repressing chromatin opening at specific genomic loci and that sustained ectopic expression of wt1 in cardiomyocytes can lead to their transformation into epicardial cells.

developmental biology↗