Biology subjects

Andrade, R. M.

Publications and source records attributed to Andrade, R. M..

3 recordsLinked to original sources

bioRxiv2021

Sulfated polysaccharides from red seaweed Gracilaria cornea induce macrophages polarization to an antitumor M1 phenotype

Marine seaweeds are a rich source of sulfated polysaccharides with several biological activities, including antitumor effect. Some polysaccharides are also described to activate macrophages (M{phi}s) to an antitumor M1-like phenotype. Here, we evaluated the capacity of sulfated galactans (SGs) extracts obtained from three seaweed species, Gracilaria cornea (Gc-E), Gracilaria birdiae (Gb-E), and Solieria filiformis (Sf-E), to activate the M{phi}s antitumor M1 phenotype. The nitric oxide production, MHCII, and CD86 (M1 markers) were evaluated to screening the bioactive SGs profile on murine M{phi}s (RAW 264.7 cells). The direct SGs antiproliferative effect was tested on melanoma B16-F10 cells. In another experimental setting, B16-F10 cells were incubated with a conditioned medium obtained from M{phi}s exposed to SGs. The three SGs tested induced NO release. Sf-E directly inhibited B16-F10 cells proliferation compared with the saline group, but Gc-E and Gb-E failed to inhibit cell proliferation. Notably, a conditioned medium (CM) of M{phi}s incubated with Gc-E and Sf-E, but not of Gb-E, inhibited the proliferation of B16-F10 cells. Gc-E also induced TNF- release and increase of M1 markers such as iNOS, MHCII, and CD86. Therefore, Gc-E activates M{phi}s to M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation.

pharmacology and toxicology↗

bioRxiv2021

The dual nature of metacommunity variability

There is increasing interest in measuring ecological stability to understand how communities and ecosystems respond to broad-scale global changes. One of the most common approaches is to quantify the variation through time in community or ecosystem aggregate attributes (e.g., total biomass), referred to as aggregate variability. It is now widely recognized that aggregate variability represents only one aspect of communities and ecosystems, and compositional variability, the changes in the relative frequency of species in an assemblage, is equally important. Recent contributions have also begun to explore ecological stability at regional spatial scales, where interconnected local communities form metacommunities, a key concept in managing complex landscapes. However, the conceptual frameworks and measures of ecological stability in space have only focused on aggregate variability, leaving a conceptual gap. Here, we address this gap with a novel framework for quantifying the aggregate and compositional variability of communities and ecosystems through space and time. We demonstrate that the compositional variability of a metacommunity depends on the degree of spatial synchrony in compositional trajectories among local communities. We then provide a conceptual framework in which compositional variability of (i) the metacommunity through time and (ii) among local communities combine into four archetype scenarios: spatial stasis (low/low); spatial synchrony (high/low); spatial asynchrony (high/high) and spatial compensation (low/high). We illustrate this framework based on numerical examples and a case study of a macroalgal metacommunity in which low spatial synchrony reduced variability in aggregate biomass at the metacommunity scale, while masking high spatial synchrony in compositional trajectories among local communities. Finally, we discuss the role of dispersal, environmental heterogeneity, species interactions and suggest future avenues. We believe this framework will be helpful for considering both aspects of variability simultaneously which is important to better understand ecological stability in natural and complex landscapes in response to environmental changes.

ecology↗

bioRxiv2020

Auranofin resistance in Toxoplasma gondii decreases the accumulation of reactive oxygen species but does not target parasite thioredoxin reductase

Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including Toxoplasma gondii. We generated auranofin resistant T. gondii lines through chemical mutagenesis in order to identify the molecular target of this drug. Resistant clones were confirmed with a competition assay using wild-type T. gondii expressing yellow fluorescence protein (YFP) as a reference strain. The predicted auranofin target, thioredoxin reductase, was not mutated in any of our resistant lines. Subsequent whole genomic sequencing analysis (WGS) did not reveal a consensus resistance locus, although many have point mutations in genes encoding redox-relevant proteins such as superoxide dismutase (TgSOD2) and ribonucleotide reductase. We investigated the SOD2 L201P mutation and found that it was not sufficient to confer resistance when introduced into wild-type parasites. Resistant clones accumulated less ROS than their wild type counterparts. Our results demonstrate that resistance to auranofin in T. gondii enhances its ability to abate oxidative stress through diverse mechanisms. This evidence supports a hypothesized mechanism of auranofin anti-parasitic activity as disruption of redox homeostasis.

microbiology↗