Biology subjects

Goncalves, P.

Publications and source records attributed to Goncalves, P..

9 recordsLinked to original sources

bioRxiv2026

Cooperative processing of visual threat across collicular pathways

Rapid defensive actions require the transformation of sensory cues into appropriate motor responses. The superior colliculus is central to this transformation, containing defined cell-types that form parallel output pathways linking visual inputs to distinct behaviors. However, whether these pathways act independently or cooperate remains unclear. Here we combine cell-type-specific inhibition, large-scale electrophysiology, and functional ultrasound imaging to determine how these pathways contribute to visually evoked defensive behaviors. Inhibiting either narrow-field or wide-field neurons impaired escape to overhead visual threats, demonstrating that both pathways contribute to escape. Recordings from downstream targets revealed a compact representation in the deeper layers of the superior colliculus that selectively distinguished visual stimuli associated with escape, whereas the lateral posterior thalamus contained a broader representation of visual stimuli. The representation of visual threat in the deeper layers of the superior colliculus predicted escape initiation and vigor in freely moving animals. Across the brain, functional ultrasound imaging showed that visual stimuli recruited distinct patterns of activity that could not be explained by response magnitude alone or by the contribution of single cell-types. Together, these results reveal a cooperative circuit architecture in which parallel pathways carry distinct but complementary signals that jointly support visually evoked escape.

neuroscience↗

bioRxiv2025

Discovery of additional ancient genome duplications in yeasts

Whole genome duplication (WGD) has had profound macroevolutionary impacts on diverse lineages1,2, preceding adaptive radiations in vertebrates3-5, teleost fish6,7, and angiosperms8,9. In contrast to the many known ancient WGDs in animals10,11 and especially plants12-14, we are aware of evidence for only four in fungi15,16. The oldest of these occurred [~]100 million years ago (mya) and is shared by [~]60 extant Saccharomycetales species17,18, including the bakers yeast Saccharomyces cerevisiae (Fig. 1). Notably, this is the only known ancient WGD in the yeast subphylum Saccharomycotina. The dearth of ancient WGD events in fungi remains a mystery15. Some studies have suggested that fungal lineages that experience chromosome19 and genome15 duplication quickly go extinct, leaving no trace in the genomic record, while others contend that the lack of known WGD is due to an absence of data15,16. Under the second hypothesis, additional sampling and deeper sequencing of fungal genomes should lead to the discovery of more WGD events. Coupling hundreds of recently published genomes from nearly every described Saccharomycotina species with three additional long-read assemblies, we discovered three novel WGD events. While the functions of retained duplicate genes originating from these events are broad, they bear many similarities to the well-known WGD that occurred in the Saccharomycetales17. Our results suggest that WGD may be a more common evolutionary force in fungi than previously believed. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/673279v1_fig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@6a8f47org.highwire.dtl.DTLVardef@1e4a790org.highwire.dtl.DTLVardef@b4e0eforg.highwire.dtl.DTLVardef@11b7795_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Three additional whole genome duplications in Saccharomycotina yeasts. Rates of gene duplication are mapped onto Saccharomycetales (left) and Dipodascales (right) phylogenies. Whole genome duplications indicated along the lineages in which they are predicted to occur. Trees have been pruned for visualization purposes. C_FIG HighlightsO_LIEvidence for three whole genome duplications (WGDs) in Dipodascales yeasts C_LIO_LIImpacts of WGD are broad but bear many similarities to the known WGD in Saccharomycetales yeasts C_LIO_LIDuplicates with many protein-protein interactions are more likely to be retained over long timescales C_LIO_LIWGD in fungi is likely underreported C_LI

evolutionary biology↗

bioRxiv2024

A comprehensive evaluation of taxonomic classifiers in marine vertebrate eDNA studies

Environmental DNA (eDNA) metabarcoding is a widely used tool for surveying marine vertebrate biodiversity. To this end, many computational tools have been released and a plethora of bioinformatic approaches are used for eDNA-based community composition analysis. Simulation studies and careful evaluation of taxonomic classifiers are essential to establish reliable benchmarks to improve accuracy and reproducibility of eDNA-based findings. Here we present a comprehensive evaluation of nine taxonomic classifiers exploring three widely used mitochondrial markers (12S rDNA, 16S rDNA, and COI) in Australian marine vertebrates. Curated reference databases and exclusion database tests were used to simulate diverse species compositions, including three positive control and two negative control datasets. Using these simulated datasets, we were able to identify between 19% to 85% of marine vertebrate species using mitochondrial markers. We show that MMSeqs2 and Metabuli generally outperform BLAST with 10% and 11% higher F1 scores for 12S and 16S rDNA markers, respectively, and that Naive Bayes Classifiers such as Mothur outperform sequence-based classifiers except MMSeqs2 for COI markers by 11%. Database exclusion tests reveal that MMSeqs2 and BLAST are less susceptible to false positives compared to Kraken2 with default parameters. Based on these findings, we recommend that MMSeqs2 is used for taxonomic classification of marine vertebrates given its ability to improve species-level assignments while reducing the number of false positives. Our work contributes to the establishment of best practices in eDNA-based biodiversity analysis to ultimately increase the reliability of this monitoring tool in the context of marine vertebrate conservation.

ecology↗

bioRxiv2023

Genomic and ecological factors shaping specialism and generalism across an entire subphylum

Organisms exhibit extensive variation in ecological niche breadth, from very narrow (specialists) to very broad (generalists). Paradigms proposed to explain this variation either invoke trade-offs between performance efficiency and breadth or underlying intrinsic or extrinsic factors. We assembled genomic (1,154 yeast strains from 1,049 species), metabolic (quantitative measures of growth of 843 species in 24 conditions), and ecological (environmental ontology of 1,088 species) data from nearly all known species of the ancient fungal subphylum Saccharomycotina to examine niche breadth evolution. We found large interspecific differences in carbon breadth stem from intrinsic differences in genes encoding specific metabolic pathways but no evidence of trade-offs and a limited role of extrinsic ecological factors. These comprehensive data argue that intrinsic factors driving microbial niche breadth variation. One-Sentence SummaryA nearly complete genomic catalog of the yeast subphylum illuminates the evolution of their diverse ecologies and metabolisms.

evolutionary biology↗

bioRxiv2023

Cholesteryl hemiazelate Identified in Cardiovascular Disease Patients Causes in vitro and in vivo Inflammation

Oxidation of polyunsaturated fatty acids (PUFA) in low-density lipoproteins (LDL) trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of unsaturated fatty acid esters of cholesterol, the effects of the oxidation end-products of these esters has been ignored in the literature. Through lipidomics analyses of the plasma of cardiovascular disease patients and human endarterectomy specimens we identified and quantified cholesteryl hemiesters (ChE), end-products of oxidation of polyunsaturated-fatty acid esters of cholesterol. Cholesteryl hemiazelate (ChA) was the most prevalent ChE identified. Importantly human monocytes, monocyte-derived macrophages (MDM) and neutrophils exhibit inflammatory features when exposed to sub-toxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as IL-1{beta} and IL-6 and modulates the surface markers profile of monocytes and MDM. In vivo, when zebrafish larvae were fed with a ChA-enriched diet they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA has pro-atherogenic properties and can be considered part of a damage-associated molecular pattern (DAMP) in the development of atherosclerosis.

pathology↗

bioRxiv2022

Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary leading to the diversification of this genus over the last 20 million years. Here, we report the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.

evolutionary biology↗

bioRxiv2021

A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-{kappa}B activity, TNF- signaling, associated with decreased gene expression of NF-{kappa}B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1 and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

immunology↗

bioRxiv2020

Multiple pathways to homothallism in closely related yeast lineages in the Basidiomycota

Sexual reproduction in fungi relies on proteins with well-known functions encoded by the mating-type (MAT) loci. In the Basidiomycota, MAT loci are often bipartite, with the P/R locus encoding pheromone precursors and pheromone receptors and the HD locus encoding heterodimerizing homeodomain transcription factors (Hd1/Hd2). The interplay between different alleles of these genes within a single species usually generates at least two compatible mating types. However, a minority of species are homothallic, reproducing sexually without an obligate need for a compatible partner. Here we examine the organization and function of the MAT loci of Cystofilobasidium capitatum, a species in the order Cystofilobasidiales, which is unusually rich in homothallic species. We determined MAT gene content and organization in C. capitatum and found that it resembles a mating type of the closely related heterothallic species Cystofilobasidium ferigula. To explain the homothallic sexual reproduction observed in C. capitatum we examined HD-protein interactions in the two Cystofilobasidium species and determined C. capitatum MAT gene expression both in a natural setting and upon heterologous expression in Phaffia rhodozyma, a homothallic species belonging to a clade sister to Cystofilobasidium. We conclude that the molecular basis for homothallism in C. capitatum appears to be distinct from that previously established for P. rhodozyma. Unlike the latter species, homothallism in C. capitatum may involve constitutive activation or dispensability of the pheromone receptor and the functional replacement of the usual Hd1/Hd2 heterodimer by an Hd2 homodimer. Overall, our results suggest that homothallism evolved multiple times within the Cystofilobasidiales. ImportanceSexual reproduction is important for the biology of eukaryotes because it strongly impacts the dynamics of genetic variation. In fungi, although sexual reproduction is usually associated with the fusion between cells belonging to different individuals (heterothallism), sometimes a single individual is capable of completing the sexual cycle alone (homothallism). Homothallic species are unusually common in a fungal lineage named Cystofilobasidiales. Here we studied the genetic bases of homothallism in one species in this lineage, Cystofilobasidium capitatum, and found it to be different in several aspects when compared to another homothallic species, Phaffia rhodozyma, belonging to the genus most closely related to Cystofilobasidium. Our results strongly suggest that homothallism evolved independently in Phaffia and Cystofilobasidium, lending support to the idea that transitions between heterothallism and homothallism are not as infrequent as previously thought. Our work also helps to establish the Cystofilobasidiales as a model lineage in which to study these transitions.

microbiology↗

bioRxiv2017

Evidence for loss and adaptive reacquisition of alcoholic fermentation in an early-derived fructophilic yeast lineage

Fructophily is a rare trait that consists in the preference for fructose over other carbon sources. Here we show that in a yeast lineage (the Wickerhamiella/Starmerella, W/S clade) formed by fructophilic species thriving in the floral niche, the acquisition of fructophily is part of a wider process of adaptation of central carbon metabolism to the high sugar environment. Coupling comparative genomics with biochemical and genetic approaches, we show that the alcoholic fermentation pathway was profoundly remodeled in the W/S clade, as genes required for alcoholic fermentation were lost and subsequently re-acquired from bacteria through horizontal gene transfer. We further show that the reinstated fermentative pathway is functional and that an enzyme required for sucrose assimilation is also of bacterial origin, reinforcing the adaptive nature of the genetic novelties identified in the W/S clade. This work shows how even central carbon metabolism can be remodeled by a surge of HGT events.

genomics↗