Biology subjects

Goncalves, C.

Publications and source records attributed to Goncalves, C..

34 records · Page 2Linked to original sources

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

Body size-dependent effects on the distribution patterns of phoretic mites of the multi-symbiont Rhynchophorus ferrugineus (Olivier, 1790) host

Phoretic mites have been found attached to different body parts of the red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790), to disperse. However, the question of how the patterns of attachment sites are formed remains intriguing. Here, we conducted the first study of RPW-associated phoretic mites in Portugal, particularly in the districts of Viana do Castelo, Braga, Porto and Aveiro in Northern Portugal (macrohabitat), and investigated the patterns of mite distribution on six body parts of RPW (microhabitat). At the macrohabitat level, we detected seven phoretic mite taxa actively using the RPW host in each of the four studied districts, all documented for the first time in association with this invasive exotic species in Portugal. However, their relative abundance (species evenness) varied between districts, as did species diversity. All examined weevils carried mites, and the prevalence of the different taxa did not differ between districts or sex of weevils. Measured by mean abundance and degree of aggregation, Centrouropoda sp. proved to be the common dominant taxon, while Acarus sp. And C. rhynchoporus were considered common subordinate taxa and Uroovobella sp., Mesostigmata, N. extremica and Dendrolaelaps sp. sparse taxa. At the microhabitat level, all taxa were present in all body parts of the RPW; the highest abundance was in a region encompassing the inner surface of the elytra and the membranous hind wings (subelytral space). Analysis of niche overlap revealed that the distribution patterns of phoretic mite taxa on the RPW were not randomly structured. In the subelytral space, interspecific coexistence of mites increased as a function of body size difference with the dominant Centrouropoda sp. We conclude that the distribution patterns of RPW-associated phoretic mites show body size-dependent effects that resulted in the dominant taxon displacing similar size taxa and accepting taxa with which it has the greatest size difference as co-habitants.

ecology↗

bioRxiv2022

Phylogenomics reveals extensive misidentification of fungal strains from the genus Aspergillus

Modern taxonomic classification is often based on phylogenetic analyses of a few molecular markers, although single-gene studies are still common. However, the use of one or few molecular markers can lead to inaccurate inferences of species history and errors in classification. Here, we leverage genome-scale molecular phylogenetics (phylogenomics) of species and populations to reconstruct evolutionary relationships in a dense dataset of 711 fungal genomes from the biomedically and technologically important genus Aspergillus. To do so, we generated a novel set of 1,362 high-quality molecular markers specific for Aspergillus and provide profile Hidden Markov Models for each, facilitating others to use these molecular markers. Examination of the resulting genome-scale phylogeny: (1) helped resolve ongoing taxonomic controversies and identified new ones; (2) revealed extensive strain misidentification, underscoring the importance of population-level sampling in species classification; and (3) identified novel lineages that may shed light on the early evolution of an important genus. These findings suggest that phylogenomics of species and populations can facilitate accurate taxonomic classifications and reconstructions of the tree of life.

evolutionary biology↗

bioRxiv2022

Disrupting peroxisomes alters lipid metabolism in melanoma and uncovers a novel therapeutic vulnerability in combination with MAPK-targeted therapies

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKi) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiates the pro-apoptotic effects of MAPKi via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Co-targeting PEX3 and UGCG selectively eliminates a subset of metabolically active, drug-tolerant CD36+ melanoma persister cells, thereby sensitizing melanoma to MAPKi and delaying resistance. Increased levels of peroxisomal genes and UGCG are found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restores MAPKi sensitivity in multiple models of therapy resistance. Finally, triple therapy comprised of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor and a MAPKi demonstrates potent anti-tumor activity in pre-clinical melanoma models, thus representing a promising approach for melanoma treatment. HighlightsO_LIInhibiting peroxisome biogenesis uncovers a metabolic vulnerability in melanoma C_LIO_LICD36+ persister melanoma cells tolerate MAPK-targeted therapy through peroxisome/UGCG mediated metabolic rewiring C_LIO_LIDual blockade of PEX3 and UGCG potentiates melanoma response to MAPK-targeted therapies and restores therapeutic sensitivity in MAPKi-resistant tumors C_LIO_LINNC 55-0396 is a PEX3-PEX19 binding inhibitor with potent anti-tumor activity in melanoma C_LI

cancer biology↗

bioRxiv2022

Experimental effects of within-brood genetic variation on parasite resistance in a wild bird host

Hosts can differ in parasite susceptibility across individuals, populations, and species. Genetic variation can influence parasite susceptibility by affecting host resistance to parasitism. For example, genetic variation among related individuals, such as within broods of offspring, might be a key factor influencing within-brood resistance to ectoparasitism. The goal of this study was to determine if within-brood variation of eastern bluebirds (Sialia sialis) affects susceptibility to ectoparasitic blowflies (Protocalliphora sialia). To address the goal, we conducted a partial cross-fostering study for which half of the nestlings were cross-fostered (experimental) or not (control). Nestling physiology (i.e., glucose, hemoglobin, and parasite-specific IgY antibody levels), morphometrics (i.e., mass, tarsus length, bill length, and first primary feather), survival, nestling status (resident versus fostered), and sex were characterized. We also quantified parasite abundance, life stage, and pupal size. We found that experimental nests had fewer parasites and more larvae than pupae compared to control nests, which suggest that within-brood genetic variation affects parasite abundance. However, this effect was driven by the sex ratio with the experimental nests, with female-biased nests having fewer parasites than male-biased nests. Treatment did not affect nestling morphometrics, physiology, or survival at the nest level. Within experimental nests, resident females had significantly higher hemoglobin levels when compared to fostered females. Resident and fostered males and fostered females had significantly higher glucose levels than resident females. Together, these results suggest that resident females were fed upon less than fostered females and may have been less stressed than males and fostered females. Overall, our study demonstrates the importance of considering within-brood variation and nestling sex in understanding host-parasite interactions.

ecology↗

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

Bagaza virus in wild birds, Portugal, 2021

Bagaza virus (BAGV) emerged in Spain, in 2010. Since then, BAGV was not reported in other European countries until September 2021, when BAGV was diagnosed by molecular methods in one corn bunting and several red-legged partridges, after abnormal mortality in Southern Portugal. Sequencing revealed high similarity with strains reported previously.

pathology↗

bioRxiv2021

Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci

BackgroundGenomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. ResultsHere, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. ConclusionTaken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.

microbiology↗

bioRxiv2021

BioKIT: a versatile toolkit for processing and analyzing diverse types of sequence data

Bioinformatic analysis--such as genome assembly quality assessment, alignment summary statistics, relative synonymous codon usage, paired-end aware quality trimming and filtering of sequencing reads, file format conversion, and processing and analysis--is integrated into diverse disciplines in the biological sciences. Several command-line pieces of software have been developed to conduct some of these individual analyses; however, the lack of a unified toolkit that conducts all these analyses can be a barrier in workflows. To address this obstacle, we introduce BioKIT, a versatile toolkit for the UNIX shell environment with 40 functions, several of which were community-sourced, that conduct routine and novel processing and analysis of genome assemblies, multiple sequence alignments, coding sequences, sequencing data, and more. To demonstrate the utility of BioKIT, we assessed the quality and characteristics of 901 eukaryotic genome assemblies, calculated alignment summary statistics for 10 phylogenomic data matrices, determined relative synonymous codon usage across 171 fungal genomes including those that use alternative genetic codes, and demonstrate that a novel metric, gene-wise relative synonymous codon usage, can accurately estimate gene-wise codon optimization. BioKIT will be helpful in facilitating and streamlining sequence analysis workflows. BioKIT is freely available under the MIT license from GitHub (https://github.com/JLSteenwyk/BioKIT), PyPi (https://pypi.org/project/jlsteenwykbiokit/), and the Anaconda Cloud (https://anaconda.org/jlsteenwyk/jlsteenwyk-biokit). Documentation, user tutorials, and instructions for requesting new features are available online (https://jlsteenwyk.com/BioKIT).

bioinformatics↗

bioRxiv2021

Phenotypic architecture of sociality and its associated genetic polymorphisms in zebrafish

Sociality is often seen as a single phenotypic trait, but it relies on motivational and cognitive components implemented by specific causal mechanisms. Hence, these components may have evolved independently, or may have been linked by phenotypic correlations driven by a shared selective pressure for increased social competence. Furthermore, these components may be domain-specific or of general domain across social and non-social contexts. Here we have characterized the phenotypic architecture of sociality in zebrafish, which has been increasingly used as a model organism in social neuroscience. For this purpose, we have behaviorally phenotyped zebrafish from different wild type lines in four tests: social tendency, social and non-social recognition, and open-field test. Our results indicate that: (1) sociality has two main components that are independent from each other (social tendency and social recognition), hence not supporting the occurrence of a sociality syndrome; (2) both social traits are phenotypically linked to non-social traits (non-social exploration and non-social memory, respectively), forming two general behavioral modules, general inspection and general recognition, and suggesting that sociality traits have been co-opted from general-domain motivational and cognitive traits. Moreover, the study of the association between genetic polymorphisms (i.e. single nucleotide polymorphisms, SNPs) and each behavioral module further supports this view, since several SNPs from a list of candidate "social" genes, are statistically associated with the general inspection (motivational), but not with a general recognition (cognitive), behavioral module. The SNPs associated with general inspection are widespread across different chromosomes and include neurotransmitters, neuromodulators, and synaptic plasticity genes, suggesting that this behavioral module is regulated by multiple genes, each of them with small effects. Together, these results support the occurrence of general domain motivational and cognitive behavioral modules in zebrafish, which have been co-opted for the social domain. Author summarySocial living has been considered one of the major transitions in evolution and it has been considered to act as a major selective force shaping the evolution of brain and behavior in animals. Sociality relies on two basic behavioral mechanisms: (1) the willingness to approach and be near others (aka social tendency); and (2) the ability to distinguish between others (aka social recognition) in order to adjust the behavior expressed during social interactions according to the identity of the interactant. There is an ongoing debate on to what extent these social abilities have specifically evolved in response to social living and are domain specific, or if they were selected as a broad response to cognitive demands and are of general domain. Here, we used zebrafish to test the domain-specific vs. general domain hypotheses and to assess the association of social tendency and social recognition with a set of candidate "social" genes (i.e. genes that have been linked to social behavior in other studies with different vertebrate species). We found that both social traits are not correlated to each other and are of general domain, and that only social tendency is associated with candidate "social" genes, suggesting that social tendency and social recognition are independent behavioral modules that rely on separate genetic architectures and that can evolve separately.

animal behavior and cognition↗

bioRxiv2020

The pleiotropic effects of the MNK1/2-eIF4E axis support immune suppression and metastasis in a model of postpartum breast cancer.

PurposeBreast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes the translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment, and in particular its activity in human PPBC, has not been explored. Experimental designWe used a combination of in vivo PPBC models and in vitro assays to study the effects of phospho-eIF4E deficiency on the pro-tumor function of select cells of the TME. Furthermore, we employed Imaging Mass Cytometry on PPBC and non-PPBC patient samples, to chart the expression of the MNK1/2-eIF4E axis components in the TME. ResultsHere, we show that phospho-eIF4E deficient (eIF4ES209A) PPBC mice are protected against lung metastasis and reveal differences in the lung immune microenvironment of the WT and eIF4ES209A mice. Moreover, we show that the expression of fibroblast-derived IL-33, an alarmin known to induce invasion, was repressed upon MNK1/2-eIF4E axis inhibition. Imaging Mass Cytometry results indicated that human PPBC contain phospho-eIF4E high-expressing tumor cells and CD8+ T cells displaying an activated dysfunctional phenotype. Finally, we block lung metastasis in PPBC mice, using combined MNK1/2 inhibition and anti-PD-1 therapy. ConclusionsThese findings implicate the involvement of the MNK1/2-eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. Translational relevancePostpartum breast cancer (PPBC) is highly aggressive. It is hypothesized that involution-induced changes in the postpartum breast microenvironment, which include an influx of inflammatory immune cells and activation of resident fibroblasts, facilitate the invasiveness of an existing neoplasm. We used imaging mass cytometry to do an in-depth profiling of the MNK1-eIF4E axis in the TME of a unique cohort of PPBC and non-PPBC patients. We observed patterns of phospho-eIF4E in non-tumor cells that were specific to the TME of PPBC. We also noted that the CD8+ T cells present in PPBC express an activated dysfunctional phenotype characterized by the co-expression of HLA-DR and PD-1. This study represents a first look at the expression of the MNK1-eIF4E axis in the stromal cells of metastatic breast cancer and has therapeutic implications as we show, in an animal model of PPBC, that MNK1/2 inhibition can be used to sensitize tumors to anti-PD1 immunotherapy.

cancer biology↗

bioRxiv2020

The MNK1/2-eIF4E axis contributes to phenotype switching, melanoma progression, and resistance to immunotherapy.

Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Melanoma plasticity exhibited as phenotype switching contributes to immunotherapy resistance, however the mechanisms are not completely understood and thus therapeutically unexploited. Here, using a transgenic melanoma mouse model, we demonstrated a critical role of the MNK1/2-eIF4E axis in melanoma plasticity and resistance to immunotherapy. We showed that phospho-eIF4E deficient murine melanomas express high levels of melanocytic antigens, with similar results verified in patient melanomas. Mechanistically, we identified that phospho-eIF4E controls the translation of NGFR, a critical effector of phenotype switching. In patients with melanoma, the expression of MKNK1, the kinase for eIF4E, positively correlated with markers of immune exhaustion. Genetic ablation of phospho-eIF4E reprogrammed the immunosuppressive microenvironment, exemplified by lowered production of inflammatory factors and increased CD8+ T cell infiltrates. Blocking phospho-eIF4E, using MNK1/2 inhibitors, offers a new strategy to inhibit melanoma plasticity and improve the survival response to anti-PD-1 immunotherapy.

cancer biology↗

bioRxiv2020

Detection of hypermucoviscous Klebsiella pneumoniae sequence type 86 capsular type K2 in South America as an unexpected cause of a fatal outbreak in captivity marmosets

After the sudden death of eleven captives marmosets in a rehabilitation center of wildlife in Sao Paulo, Brazil, histological and microbiological study was conducted. Liver, spleen, intestine, central nervous system, lung, thymus, stomach, testicle tissues were analyzed by light microscopy and microbial cultures were conducted. Environmental cultures were also performed. Prophylactic antimicrobial therapy, restricted access to marmosets cages with dedicated staff, and additional sanitization of animals fruits were implemented. Histological findings were compatible with hyperacute septicemia, and microbiological cultures and molecular tests identified the etiologic agent as hypermucoviscous sequence type 86 capsular type K2 K. pneumoniae for the first time in South America. Implementation of prompt containment measures led to successful control of this outbreak. Detection of a hypervirulent and zoonotic pathogen, such as hypermucoviscous K. pneumoniae ST86 K2, in an unexpected and human interface reservoir underscores its potential threat in public health settings.

microbiology↗

bioRxiv2018

What is known about modified insects for disease prevention?: a systematic review

The modification and release of insects to suppress or replace natural insect vectors constitutes a promising tool for vector control and disease prevention, facing the unprecedented global emergence of vector-borne diseases. Little is known regarding these innovative modification strategies and available evidence is not standardized turning it difficult to reflect on their actual efficacy and eventual effects.\n\nThis work conducted a systematic review, gathering and analyzing research articles from PubMed and Biblioteca Virtual em Saude databases whose results directly report efficacy and effects of the use of modified insects for disease prevention until 2016. Within more than 1500 publications that were screened a total of 349 where analyzed.\n\nA total of 12/3.4% reported field-based evidence, and 41/11.7% covered modification stretagies efficacy after insects release, their epidemiology impact or its long-term efficacy. Examples of successful results were the replacement of natural field populations by wolbachia-infected mosquitoes in 5 weeks, and the elimination of a population in laboratory cages after transgenic mosquitoes release over 10-20 weeks. Variability in the effective results were described (90/25.7%) questioning its reproducibility in different settings. We also found 38/10.9% publications reporting reversal outcomes, such as an increase of vector population after release. Ecological effects such as horizontal transfer events to non-target species (54/15.5%), and wolbachia-induced worsening pathogenesis on mammal filarial diseases (10/2.9%) were also reported.\n\nPresent work revealed promising outcomes of both suppressing and replacing approaches. However, it also revealed a need of field-based evidence mainly regarding epidemiologic and long-term impact of insect modification strategies. It pointed out some eventual irreversible and important effects that must not be ignored when considering open-field releases, and that may constitute constraints to generate the missing field evidence. Moreover, the level of variability of existing evidence suggests the need of local/specific evidence in each setting of an eventual release.\n\nAuthor summaryInnovative strategies are needed to arrest the unprecedented increase of vector-borne disease incidence, distribution and severity. Several modification techniques are being tried all over the world. However this is still an emergent topic with scarce available information and of complex understanding.\n\nPresent work is the unique structured review regarding the use of modified insects for vector-borne disease prevention, bringing neutral and robust evidence that will contribute with critical insights regarding these approaches.\n\nHere we explored more than 1200 publications and analyzed 349 publications on this subject, describing the actual efficacy and reported effects of several modification strategies. More than 30 categories were reported such as, the type of modification, the year of the publication, the species were results were tested, the type of study, and also type of Efficacy Outcome (from modification to long-term) and/or the type of Effects Outcome (from physiologic to ecologic effects). Analysis revealed promising outcomes regarding vector-control and disease prevention. However insects modification strategies still lack field-based evidence mainly regarding epidemiological and long-term efficacy. Eventual reversal outcomes on disease transmission, or irreversible biological effects (including horizontal transfer to non-target species or worsening pathogenesis in particular diseases in mammals), were also described. These effects need to be explored, dispelled or resolved before field trials occur in human residential areas. Some of these questions could only have a robust answer if these strategies would be implemented, needing to take the risk to observe reversal outcomes and/or irreversible effects. These findings reflect the big dilemma that is under the use of modified insects to prevent vector-borne diseases. Findings could support health authorities in decision-making and regulatory committees during advisory processes, by evaluating the pros/cons of each modifying technique for a particular setting. Moreover they could also summarize what is crucial to inform to communities if planning open field releases in residential areas.

ecology↗

bioRxiv2018

Strong replicators associated with open chromatin are sufficient to establish an early replicating domain

Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into topologically associating domains. However, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late replicating region for earlier replication. When inserted side-by-side, these modules acted in cooperation, with similar effects on two late-replicating regions. Targeted insertions of these two modules at two chromosomal sites separated by 30 kb brought these two modules into close physical proximity and induced the formation of an early-replicating domain. Thus, combinations of strong origins and cis-elements capable of opening the chromatin structure are the basic units of early-replicating domains, and are absent from late-replicated regions. These findings are consistent with those of genome-wide studies mapping strong initiation sites and open chromatin marks in vertebrate genomes.

molecular biology↗

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↗